TY  - CONF
AU  - Popov Aleksandrov, Aleksandra
AU  - Mirkov, Ivana
AU  - Tucović, Dina
AU  - Kulaš, Jelena
AU  - Ninkov, Marina
AU  - Popović, Dušanka
AU  - Malešević, Anastasija
AU  - Kataranovski, Milena
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5141
AB  - Имунски систем је осетљива мета токсичног деловања загађивача из спољашње средине. Интеракција загађивача са ћелијама имунског система може довести до поремећаја имунолошки-посредоване ткивне хомеостазе са штетним здравственим ефектима. Тешки метали спадају у најопасније загађиваче међу којима је кадмијум (Cd) један од најтоксичнијих, с обзиром на податке који показују да је токсичан при ниским концентрацијама и на студије које га повезују са имунолошки-посредованим поремећајима. Кадмијум најчешће доспева у организам оралним путем, уношењем контаминиране хране и воде, након чега се путем крви дистрибуира до свих органа где се депонује. На пацовском моделу продужене оралне примене Cd (дозе релевантне за срединску изложеност) показали смо да Cd остварује имуномодулаторне ефекте локално (у цревном тракту) али и у удаљеним ткивима плућа и коже. Оштећење ткива и инфламација (повећан оксидативни стрес и продукција проинфламаторних цитокина) запажени су у сва три органа. Поремећај имунске хомеостазе у цревима огледа се и у стимулацији ефекторског имунског одговора (пролиферација, IFN-γ, IL-17) у чворовима који дренирају ову регију. Инфламација у кожи и повећана оксидативна и проинфламаторна активност епидермних ћелија коинцидирају са повећаном реактивношћу овог ткива на контактни алерген. Утичући на активност имунског система орално примењен Cd може да мења његову функцију и последично осетљивост на развој болести, што указује да Cd може представљати озбиљну претњу по здравље људи.
AB  - Имунски систем је осетљива мета токсичног деловања загађивача из спољашње средине. Интеракција загађивача са ћелијама имунског система може довести до поремећаја имунолошки-посредоване ткивне хомеостазе са штетним здравственим ефектима. Тешки метали спадају у најопасније загађиваче међу којима је кадмијум (Cd) један од најтоксичнијих, с обзиром на податке који показују да је токсичан при ниским концентрацијама и на студије које га повезују са имунолошки-посредованим поремећајима. Кадмијум најчешће доспева у организам оралним путем, уношењем контаминиране хране и воде, након чега се путем крви дистрибуира до свих органа где се депонује. На пацовском моделу продужене оралне примене Cd (дозе релевантне за срединску изложеност) показали смо да Cd остварује имуномодулаторне ефекте локално (у цревном тракту) али и у удаљеним ткивима плућа и коже. Оштећење ткива и инфламација (повећан оксидативни стрес и продукција проинфламаторних цитокина) запажени су у сва три органа. Поремећај имунске хомеостазе у цревима огледа се и у стимулацији ефекторског имунског одговора (пролиферација, IFN-γ, IL-17) у чворовима који дренирају ову регију. Инфламација у кожи и повећана оксидативна и проинфламаторна активност епидермних ћелија коинцидирају са повећаном реактивношћу овог ткива на контактни алерген. Утичући на активност имунског система орално примењен Cd може да мења његову функцију и последично осетљивост на развој болести, што указује да Cd може представљати озбиљну претњу по здравље људи.
PB  - Belgrade: Serbian Biological Society
C3  - Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
T1  - Imunomodulatorni efekti zagađivača iz spoljašnje sredine:primer teškog metala kadmijuma
T1  - Имуномодулаторни ефекти загађивача из спољашње средине:пример тешког метала кадмијума
SP  - 114
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5141
ER  - 

@conference{
author = "Popov Aleksandrov, Aleksandra and Mirkov, Ivana and Tucović, Dina and Kulaš, Jelena and Ninkov, Marina and Popović, Dušanka and Malešević, Anastasija and Kataranovski, Milena",
year = "2022",
abstract = "Имунски систем је осетљива мета токсичног деловања загађивача из спољашње средине. Интеракција загађивача са ћелијама имунског система може довести до поремећаја имунолошки-посредоване ткивне хомеостазе са штетним здравственим ефектима. Тешки метали спадају у најопасније загађиваче међу којима је кадмијум (Cd) један од најтоксичнијих, с обзиром на податке који показују да је токсичан при ниским концентрацијама и на студије које га повезују са имунолошки-посредованим поремећајима. Кадмијум најчешће доспева у организам оралним путем, уношењем контаминиране хране и воде, након чега се путем крви дистрибуира до свих органа где се депонује. На пацовском моделу продужене оралне примене Cd (дозе релевантне за срединску изложеност) показали смо да Cd остварује имуномодулаторне ефекте локално (у цревном тракту) али и у удаљеним ткивима плућа и коже. Оштећење ткива и инфламација (повећан оксидативни стрес и продукција проинфламаторних цитокина) запажени су у сва три органа. Поремећај имунске хомеостазе у цревима огледа се и у стимулацији ефекторског имунског одговора (пролиферација, IFN-γ, IL-17) у чворовима који дренирају ову регију. Инфламација у кожи и повећана оксидативна и проинфламаторна активност епидермних ћелија коинцидирају са повећаном реактивношћу овог ткива на контактни алерген. Утичући на активност имунског система орално примењен Cd може да мења његову функцију и последично осетљивост на развој болести, што указује да Cd може представљати озбиљну претњу по здравље људи., Имунски систем је осетљива мета токсичног деловања загађивача из спољашње средине. Интеракција загађивача са ћелијама имунског система може довести до поремећаја имунолошки-посредоване ткивне хомеостазе са штетним здравственим ефектима. Тешки метали спадају у најопасније загађиваче међу којима је кадмијум (Cd) један од најтоксичнијих, с обзиром на податке који показују да је токсичан при ниским концентрацијама и на студије које га повезују са имунолошки-посредованим поремећајима. Кадмијум најчешће доспева у организам оралним путем, уношењем контаминиране хране и воде, након чега се путем крви дистрибуира до свих органа где се депонује. На пацовском моделу продужене оралне примене Cd (дозе релевантне за срединску изложеност) показали смо да Cd остварује имуномодулаторне ефекте локално (у цревном тракту) али и у удаљеним ткивима плућа и коже. Оштећење ткива и инфламација (повећан оксидативни стрес и продукција проинфламаторних цитокина) запажени су у сва три органа. Поремећај имунске хомеостазе у цревима огледа се и у стимулацији ефекторског имунског одговора (пролиферација, IFN-γ, IL-17) у чворовима који дренирају ову регију. Инфламација у кожи и повећана оксидативна и проинфламаторна активност епидермних ћелија коинцидирају са повећаном реактивношћу овог ткива на контактни алерген. Утичући на активност имунског система орално примењен Cd може да мења његову функцију и последично осетљивост на развој болести, што указује да Cd може представљати озбиљну претњу по здравље људи.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia",
title = "Imunomodulatorni efekti zagađivača iz spoljašnje sredine:primer teškog metala kadmijuma, Имуномодулаторни ефекти загађивача из спољашње средине:пример тешког метала кадмијума",
pages = "114",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5141"
}

Popov Aleksandrov, A., Mirkov, I., Tucović, D., Kulaš, J., Ninkov, M., Popović, D., Malešević, A.,& Kataranovski, M.. (2022). Imunomodulatorni efekti zagađivača iz spoljašnje sredine:primer teškog metala kadmijuma. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
Belgrade: Serbian Biological Society., 114.
https://hdl.handle.net/21.15107/rcub_ibiss_5141

Popov Aleksandrov A, Mirkov I, Tucović D, Kulaš J, Ninkov M, Popović D, Malešević A, Kataranovski M. Imunomodulatorni efekti zagađivača iz spoljašnje sredine:primer teškog metala kadmijuma. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia. 2022;:114.
https://hdl.handle.net/21.15107/rcub_ibiss_5141 .

Popov Aleksandrov, Aleksandra, Mirkov, Ivana, Tucović, Dina, Kulaš, Jelena, Ninkov, Marina, Popović, Dušanka, Malešević, Anastasija, Kataranovski, Milena, "Imunomodulatorni efekti zagađivača iz spoljašnje sredine:primer teškog metala kadmijuma" in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia (2022):114,
https://hdl.handle.net/21.15107/rcub_ibiss_5141 .

TY  - JOUR
AU  - Popov Aleksandrov, Aleksandra
AU  - Mirkov, Ivana
AU  - Tucović, Dina
AU  - Kulaš, Jelena
AU  - Zeljković, Milica
AU  - Popović, Dušanka
AU  - Ninkov, Marina
AU  - Janković, Srđa
AU  - Kataranovski, Milena
PY  - 2021
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0165247821001644
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4664
AB  - Cadmium (Cd) represents a unique hazard because of the long biological half-life in humans (20-30 years). This metal accumulates in organs causing a continuum of responses, with organ disease/failure as extreme outcome. Some of the cellular and molecular alterations in target tissues can be related to immune-modulating potential of Cd. This metal may cause adverse responses in which components of the immune system function as both mediators and effectors of Cd tissue toxicity, which, in combination with Cd-induced alterations in homeostatic reparative activities may contribute to tissue dysfunction. In this work, current knowledge concerning inflammatory/autoimmune disease manifestations found to be related with cadmium exposure are summarized. Along with epidemiological evidence, animal and in vitro data are presented, with focus on cellular and molecular immune mechanisms potentially relevant for the disease susceptibility, disease promotion, or facilitating development of pre-existing pathologies.
PB  - Elsevier B.V.
T2  - Immunology Letters
T1  - Immunomodulation by heavy metals as a contributing factor to inflammatory diseases and autoimmune reactions: Cadmium as an example.
VL  - 240
DO  - 10.1016/j.imlet.2021.10.003
SP  - 106
EP  - 122
ER  - 

@article{
author = "Popov Aleksandrov, Aleksandra and Mirkov, Ivana and Tucović, Dina and Kulaš, Jelena and Zeljković, Milica and Popović, Dušanka and Ninkov, Marina and Janković, Srđa and Kataranovski, Milena",
year = "2021",
abstract = "Cadmium (Cd) represents a unique hazard because of the long biological half-life in humans (20-30 years). This metal accumulates in organs causing a continuum of responses, with organ disease/failure as extreme outcome. Some of the cellular and molecular alterations in target tissues can be related to immune-modulating potential of Cd. This metal may cause adverse responses in which components of the immune system function as both mediators and effectors of Cd tissue toxicity, which, in combination with Cd-induced alterations in homeostatic reparative activities may contribute to tissue dysfunction. In this work, current knowledge concerning inflammatory/autoimmune disease manifestations found to be related with cadmium exposure are summarized. Along with epidemiological evidence, animal and in vitro data are presented, with focus on cellular and molecular immune mechanisms potentially relevant for the disease susceptibility, disease promotion, or facilitating development of pre-existing pathologies.",
publisher = "Elsevier B.V.",
journal = "Immunology Letters",
title = "Immunomodulation by heavy metals as a contributing factor to inflammatory diseases and autoimmune reactions: Cadmium as an example.",
volume = "240",
doi = "10.1016/j.imlet.2021.10.003",
pages = "106-122"
}

Popov Aleksandrov, A., Mirkov, I., Tucović, D., Kulaš, J., Zeljković, M., Popović, D., Ninkov, M., Janković, S.,& Kataranovski, M.. (2021). Immunomodulation by heavy metals as a contributing factor to inflammatory diseases and autoimmune reactions: Cadmium as an example.. in Immunology Letters
Elsevier B.V.., 240, 106-122.
https://doi.org/10.1016/j.imlet.2021.10.003

Popov Aleksandrov A, Mirkov I, Tucović D, Kulaš J, Zeljković M, Popović D, Ninkov M, Janković S, Kataranovski M. Immunomodulation by heavy metals as a contributing factor to inflammatory diseases and autoimmune reactions: Cadmium as an example.. in Immunology Letters. 2021;240:106-122.
doi:10.1016/j.imlet.2021.10.003 .

Popov Aleksandrov, Aleksandra, Mirkov, Ivana, Tucović, Dina, Kulaš, Jelena, Zeljković, Milica, Popović, Dušanka, Ninkov, Marina, Janković, Srđa, Kataranovski, Milena, "Immunomodulation by heavy metals as a contributing factor to inflammatory diseases and autoimmune reactions: Cadmium as an example." in Immunology Letters, 240 (2021):106-122,
https://doi.org/10.1016/j.imlet.2021.10.003 . .

TY  - JOUR
AU  - Mirkov, Ivana
AU  - Popov Aleksandrov, Aleksandra
AU  - Ninkov, Marina
AU  - Tucović, Dina
AU  - Kulaš, Jelena
AU  - Zeljković, Milica
AU  - Popović, Dušanka
AU  - Kataranovski, Milena
PY  - 2021
UR  - http://www.ncbi.nlm.nih.gov/pubmed/33508420
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4150
AB  - Cadmium (Cd) has been listed as one of the most toxic substances affecting numerous tissues/organs, including the immune system. Due to variations in studies examining Cd effects on the immune system (exposure regime, experimental systems, immune endpoint measured), data on Cd immunotoxicity in humans and experimental animals are inconsistent. However, it is clear that Cd can affect cells of the immune system and can modulate some immune responses. Due to the complex nature of the immune system and its activities which are determined by multiple interactions, the underlying mechanisms involved in the immunotoxicity of this metal are still vague. Here, the current knowledge regarding the interaction of Cd with cells of the immune system, which may affect immune responses as well as potential mechanisms of consequent biological effects of such activities, is reviewed. Tissue injury caused by Cd-induced effects on innate cell activities depicts components of the immune system as mediators/effectors of Cd tissue toxicity. Cd-induced immune alterations, which may compromise host defense against pathogenic microorganisms and homeostatic reparative activities, stress this metal as an important health hazard.
PB  - Elsevier BV
T2  - Food and Chemical Toxicology
T1  - Immunotoxicology of cadmium: Cells of the immune system as targets and effectors of cadmium toxicity.
VL  - 149
DO  - 10.1016/j.fct.2021.112026
SP  - 112026
ER  - 

@article{
author = "Mirkov, Ivana and Popov Aleksandrov, Aleksandra and Ninkov, Marina and Tucović, Dina and Kulaš, Jelena and Zeljković, Milica and Popović, Dušanka and Kataranovski, Milena",
year = "2021",
abstract = "Cadmium (Cd) has been listed as one of the most toxic substances affecting numerous tissues/organs, including the immune system. Due to variations in studies examining Cd effects on the immune system (exposure regime, experimental systems, immune endpoint measured), data on Cd immunotoxicity in humans and experimental animals are inconsistent. However, it is clear that Cd can affect cells of the immune system and can modulate some immune responses. Due to the complex nature of the immune system and its activities which are determined by multiple interactions, the underlying mechanisms involved in the immunotoxicity of this metal are still vague. Here, the current knowledge regarding the interaction of Cd with cells of the immune system, which may affect immune responses as well as potential mechanisms of consequent biological effects of such activities, is reviewed. Tissue injury caused by Cd-induced effects on innate cell activities depicts components of the immune system as mediators/effectors of Cd tissue toxicity. Cd-induced immune alterations, which may compromise host defense against pathogenic microorganisms and homeostatic reparative activities, stress this metal as an important health hazard.",
publisher = "Elsevier BV",
journal = "Food and Chemical Toxicology",
title = "Immunotoxicology of cadmium: Cells of the immune system as targets and effectors of cadmium toxicity.",
volume = "149",
doi = "10.1016/j.fct.2021.112026",
pages = "112026"
}

Mirkov, I., Popov Aleksandrov, A., Ninkov, M., Tucović, D., Kulaš, J., Zeljković, M., Popović, D.,& Kataranovski, M.. (2021). Immunotoxicology of cadmium: Cells of the immune system as targets and effectors of cadmium toxicity.. in Food and Chemical Toxicology
Elsevier BV., 149, 112026.
https://doi.org/10.1016/j.fct.2021.112026

Mirkov I, Popov Aleksandrov A, Ninkov M, Tucović D, Kulaš J, Zeljković M, Popović D, Kataranovski M. Immunotoxicology of cadmium: Cells of the immune system as targets and effectors of cadmium toxicity.. in Food and Chemical Toxicology. 2021;149:112026.
doi:10.1016/j.fct.2021.112026 .

Mirkov, Ivana, Popov Aleksandrov, Aleksandra, Ninkov, Marina, Tucović, Dina, Kulaš, Jelena, Zeljković, Milica, Popović, Dušanka, Kataranovski, Milena, "Immunotoxicology of cadmium: Cells of the immune system as targets and effectors of cadmium toxicity." in Food and Chemical Toxicology, 149 (2021):112026,
https://doi.org/10.1016/j.fct.2021.112026 . .

TY  - JOUR
AU  - Popov Aleksandrov, Aleksandra
AU  - Mirkov, Ivana
AU  - Tucović, Dina
AU  - Kulaš, Jelena
AU  - Ninkov, Marina
AU  - Kataranovski, Milena
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4076
AB  - Cadmium (Cd) is a toxic heavy metal that when absorbed into the body causes nephrotoxicity and effects in other tissues.Anatomical barrier tissues are tissues that prevent the entry of pathogens and include skin, mucus membranes and the immune system. The adverse effects of Cd-induced immune cell's activity are the most extensively studied in the kidneys and the liver. There are though fewer data relating the effect of this metal on the other tissues, particularly in those in which cells of the immune system form local circuits of tissue defense, maintaining immune-mediated homeostasis. In this work, data on the direct and indirect effects of Cd on anatomical barrier tissue of inner and outer body surfaces (the lungs, gut, reproductive organs, and skin) were summarized.
PB  - Elsevier Ireland Ltd
T2  - Toxicology Letters
T1  - Cadmium and immunologically-mediated homeostasis of anatomical barrier tissues
VL  - 337
DO  - 10.1016/j.toxlet.2020.11.008
SP  - 38
EP  - 45
ER  - 

@article{
author = "Popov Aleksandrov, Aleksandra and Mirkov, Ivana and Tucović, Dina and Kulaš, Jelena and Ninkov, Marina and Kataranovski, Milena",
year = "2021",
abstract = "Cadmium (Cd) is a toxic heavy metal that when absorbed into the body causes nephrotoxicity and effects in other tissues.Anatomical barrier tissues are tissues that prevent the entry of pathogens and include skin, mucus membranes and the immune system. The adverse effects of Cd-induced immune cell's activity are the most extensively studied in the kidneys and the liver. There are though fewer data relating the effect of this metal on the other tissues, particularly in those in which cells of the immune system form local circuits of tissue defense, maintaining immune-mediated homeostasis. In this work, data on the direct and indirect effects of Cd on anatomical barrier tissue of inner and outer body surfaces (the lungs, gut, reproductive organs, and skin) were summarized.",
publisher = "Elsevier Ireland Ltd",
journal = "Toxicology Letters",
title = "Cadmium and immunologically-mediated homeostasis of anatomical barrier tissues",
volume = "337",
doi = "10.1016/j.toxlet.2020.11.008",
pages = "38-45"
}

Popov Aleksandrov, A., Mirkov, I., Tucović, D., Kulaš, J., Ninkov, M.,& Kataranovski, M.. (2021). Cadmium and immunologically-mediated homeostasis of anatomical barrier tissues. in Toxicology Letters
Elsevier Ireland Ltd., 337, 38-45.
https://doi.org/10.1016/j.toxlet.2020.11.008

Popov Aleksandrov A, Mirkov I, Tucović D, Kulaš J, Ninkov M, Kataranovski M. Cadmium and immunologically-mediated homeostasis of anatomical barrier tissues. in Toxicology Letters. 2021;337:38-45.
doi:10.1016/j.toxlet.2020.11.008 .

Popov Aleksandrov, Aleksandra, Mirkov, Ivana, Tucović, Dina, Kulaš, Jelena, Ninkov, Marina, Kataranovski, Milena, "Cadmium and immunologically-mediated homeostasis of anatomical barrier tissues" in Toxicology Letters, 337 (2021):38-45,
https://doi.org/10.1016/j.toxlet.2020.11.008 . .

TY  - JOUR
AU  - Kulaš, Jelena
AU  - Ninkov, Marina
AU  - Tucović, Dina
AU  - Popov Aleksandrov, Aleksandra
AU  - Ukropina, Mirela
AU  - Cakić Milošević, Maja
AU  - Mutić, Jelena
AU  - Kataranovski, Milena
AU  - Mirkov, Ivana
PY  - 2019
UR  - http://www.besjournal.com/en/article/doi/10.3967/bes2019.068
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3470
AB  - OBJECTIVE The aim of this study is to investigate the effects of oral cadmium (Cd) ingestion on the pulmonary immune response. METHODS Determination of Cd content in lungs and histopathological evaluation of the tissue was performed in rats following 30-day oral Cd administration (5 and 50 mg/L). Antioxidant enzyme defense (superoxide dismutase and catalase), cell infiltration, and production of tumor necrosis factor (TNF) and interferon (IFN)-γ, as well as the activity of myeloperoxidase (MPO), nitric oxide (NO), and various cytokines [interleukin (IL)-1β, IL-6, IL-10, and IL-17] were investigated. RESULTS Cd caused tissue damage and cell infiltration in the lungs, and this damage was more pronounced at higher doses. Cd deposition resulted in lung inflammation characterized by a dose-dependent IL-1β increase in lung homogenates, increased TNF levels at both doses, and IL-6 stimulation at low doses with inhibition observed at higher doses. Cd exerted differential effects on lung leukocytes isolated by enzyme digestion, and these effects were characterized by a lack of change in the production of reactive oxygen and nitrogen species, an inhibition of IL-1β and TNF, and stimulation of MPO and IFN-γ. The higher capacity of Cd-exposed lung cells to respond to the opportunistic pathogen Staphylococcus epidermidis was demonstrated in vitro. CONCLUSION The potential of ingested Cd to exert both proinflammatory and immunosuppressive effects on pulmonary tissue inflammation and immune reactivity highlights the complex immunomodulatory actions of this metal.
PB  - Biomedical and Environmental Sciences
T2  - Biomedical and Environmental Sciences
T1  - Subchronic Oral Cadmium Exposure Exerts both Stimulatory and Suppressive Effects on Pulmonary Inflammation/Immune Reactivity in Rats.
IS  - 7
VL  - 32
DO  - 10.3967/bes2019.068
SP  - 508
EP  - 519
ER  - 

@article{
author = "Kulaš, Jelena and Ninkov, Marina and Tucović, Dina and Popov Aleksandrov, Aleksandra and Ukropina, Mirela and Cakić Milošević, Maja and Mutić, Jelena and Kataranovski, Milena and Mirkov, Ivana",
year = "2019",
abstract = "OBJECTIVE The aim of this study is to investigate the effects of oral cadmium (Cd) ingestion on the pulmonary immune response. METHODS Determination of Cd content in lungs and histopathological evaluation of the tissue was performed in rats following 30-day oral Cd administration (5 and 50 mg/L). Antioxidant enzyme defense (superoxide dismutase and catalase), cell infiltration, and production of tumor necrosis factor (TNF) and interferon (IFN)-γ, as well as the activity of myeloperoxidase (MPO), nitric oxide (NO), and various cytokines [interleukin (IL)-1β, IL-6, IL-10, and IL-17] were investigated. RESULTS Cd caused tissue damage and cell infiltration in the lungs, and this damage was more pronounced at higher doses. Cd deposition resulted in lung inflammation characterized by a dose-dependent IL-1β increase in lung homogenates, increased TNF levels at both doses, and IL-6 stimulation at low doses with inhibition observed at higher doses. Cd exerted differential effects on lung leukocytes isolated by enzyme digestion, and these effects were characterized by a lack of change in the production of reactive oxygen and nitrogen species, an inhibition of IL-1β and TNF, and stimulation of MPO and IFN-γ. The higher capacity of Cd-exposed lung cells to respond to the opportunistic pathogen Staphylococcus epidermidis was demonstrated in vitro. CONCLUSION The potential of ingested Cd to exert both proinflammatory and immunosuppressive effects on pulmonary tissue inflammation and immune reactivity highlights the complex immunomodulatory actions of this metal.",
publisher = "Biomedical and Environmental Sciences",
journal = "Biomedical and Environmental Sciences",
title = "Subchronic Oral Cadmium Exposure Exerts both Stimulatory and Suppressive Effects on Pulmonary Inflammation/Immune Reactivity in Rats.",
number = "7",
volume = "32",
doi = "10.3967/bes2019.068",
pages = "508-519"
}

Kulaš, J., Ninkov, M., Tucović, D., Popov Aleksandrov, A., Ukropina, M., Cakić Milošević, M., Mutić, J., Kataranovski, M.,& Mirkov, I.. (2019). Subchronic Oral Cadmium Exposure Exerts both Stimulatory and Suppressive Effects on Pulmonary Inflammation/Immune Reactivity in Rats.. in Biomedical and Environmental Sciences
Biomedical and Environmental Sciences., 32(7), 508-519.
https://doi.org/10.3967/bes2019.068

Kulaš J, Ninkov M, Tucović D, Popov Aleksandrov A, Ukropina M, Cakić Milošević M, Mutić J, Kataranovski M, Mirkov I. Subchronic Oral Cadmium Exposure Exerts both Stimulatory and Suppressive Effects on Pulmonary Inflammation/Immune Reactivity in Rats.. in Biomedical and Environmental Sciences. 2019;32(7):508-519.
doi:10.3967/bes2019.068 .

Kulaš, Jelena, Ninkov, Marina, Tucović, Dina, Popov Aleksandrov, Aleksandra, Ukropina, Mirela, Cakić Milošević, Maja, Mutić, Jelena, Kataranovski, Milena, Mirkov, Ivana, "Subchronic Oral Cadmium Exposure Exerts both Stimulatory and Suppressive Effects on Pulmonary Inflammation/Immune Reactivity in Rats." in Biomedical and Environmental Sciences, 32, no. 7 (2019):508-519,
https://doi.org/10.3967/bes2019.068 . .

TY  - CONF
AU  - Mileusnić, Dina
AU  - Popov Aleksandrov, Aleksandra
AU  - Mirkov, Ivana
AU  - Ninkov, Marina
AU  - Kulaš, Jelena
AU  - Vukojević, Vesna
AU  - Đurđić, Slađana
AU  - Mutić, Jelena
AU  - Kataranovski, Milena
PY  - 2018
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4855
AB  - Epidemiological studies indicate a possible link between cadmium (Cd) ingested through food and various pathologies / diseases. There is no such data when it comes to skin, although the deposition of this metal in hair is used as a biomarker of human exposure. Only one study has shown the effect of orally administered Cd on wound healing, but the effects on other homeostatic skin activities, including immune, have not been investigated. In order to investigate the potential immunomodulatory effect of this heavy metal on the skin, DA strain rats were exposed to subchronic (30 days) oral intake of cadmium (in drinking water, 5 mg / l and 50 mg / l).Cd was deposited in this tissue and led to oxidative stress, judging by the increase in antioxidant enzymes (SOD and CAT), structural changes in the skin, as well as the presence / activation of innate immune cells. Higher concentrations of deposited Cd in the epidermis compared to the dermis resulted in a stress response at the epidermal cell (EC) level, manifested by increased mRNA expression for metallothioneins (MT-1 and MT-2) and decreased GSH after a higher dose of CdThis metal also led to the manifestation of signs of inflammation, judging by the increased expression of mRNA for iNOS and IL-1β and the production of NO and IL-1β, at a lower dose, and mRNA and IL-6 and TNF protein product at a higher dose. On the other hand, Cd led to increased production of the regulatory cytokine IL-10 (at higher doses). Increased IL-17 production was observed in EC cultures isolated from the skin of rats exposed to 50 mg / l, while the amount of cytokine produced further increased in EC co-culture with lymph node lymphocytes after ConA stimulation (both doses).Cd present in the skin also increased the ability of the EC to respond to the application of the contact allergen DNCB, judging by the increase in IL-6 and TNF (at both doses), while IL-1β remained unchanged. The presented results show a generally proinflammatory effect of Cd on epidermal cells and indicate the potential of orally ingested Cd to modulate immune responses in the skin.
PB  - Belgrade: Immunological Society of Serbia
C3  - Svetski dan imunologije; 2018 Apr 26; Belgrade, Serbia
T1  - Oral cadmium intake affect skin immune ractivity
T1  - Oralni unos kadmijuma utiče na imunsku reaktivnost kože
SP  - 24
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4855
ER  - 

@conference{
author = "Mileusnić, Dina and Popov Aleksandrov, Aleksandra and Mirkov, Ivana and Ninkov, Marina and Kulaš, Jelena and Vukojević, Vesna and Đurđić, Slađana and Mutić, Jelena and Kataranovski, Milena",
year = "2018",
abstract = "Epidemiological studies indicate a possible link between cadmium (Cd) ingested through food and various pathologies / diseases. There is no such data when it comes to skin, although the deposition of this metal in hair is used as a biomarker of human exposure. Only one study has shown the effect of orally administered Cd on wound healing, but the effects on other homeostatic skin activities, including immune, have not been investigated. In order to investigate the potential immunomodulatory effect of this heavy metal on the skin, DA strain rats were exposed to subchronic (30 days) oral intake of cadmium (in drinking water, 5 mg / l and 50 mg / l).Cd was deposited in this tissue and led to oxidative stress, judging by the increase in antioxidant enzymes (SOD and CAT), structural changes in the skin, as well as the presence / activation of innate immune cells. Higher concentrations of deposited Cd in the epidermis compared to the dermis resulted in a stress response at the epidermal cell (EC) level, manifested by increased mRNA expression for metallothioneins (MT-1 and MT-2) and decreased GSH after a higher dose of CdThis metal also led to the manifestation of signs of inflammation, judging by the increased expression of mRNA for iNOS and IL-1β and the production of NO and IL-1β, at a lower dose, and mRNA and IL-6 and TNF protein product at a higher dose. On the other hand, Cd led to increased production of the regulatory cytokine IL-10 (at higher doses). Increased IL-17 production was observed in EC cultures isolated from the skin of rats exposed to 50 mg / l, while the amount of cytokine produced further increased in EC co-culture with lymph node lymphocytes after ConA stimulation (both doses).Cd present in the skin also increased the ability of the EC to respond to the application of the contact allergen DNCB, judging by the increase in IL-6 and TNF (at both doses), while IL-1β remained unchanged. The presented results show a generally proinflammatory effect of Cd on epidermal cells and indicate the potential of orally ingested Cd to modulate immune responses in the skin.",
publisher = "Belgrade: Immunological Society of Serbia",
journal = "Svetski dan imunologije; 2018 Apr 26; Belgrade, Serbia",
title = "Oral cadmium intake affect skin immune ractivity, Oralni unos kadmijuma utiče na imunsku reaktivnost kože",
pages = "24",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4855"
}

Mileusnić, D., Popov Aleksandrov, A., Mirkov, I., Ninkov, M., Kulaš, J., Vukojević, V., Đurđić, S., Mutić, J.,& Kataranovski, M.. (2018). Oral cadmium intake affect skin immune ractivity. in Svetski dan imunologije; 2018 Apr 26; Belgrade, Serbia
Belgrade: Immunological Society of Serbia., 24.
https://hdl.handle.net/21.15107/rcub_ibiss_4855

Mileusnić D, Popov Aleksandrov A, Mirkov I, Ninkov M, Kulaš J, Vukojević V, Đurđić S, Mutić J, Kataranovski M. Oral cadmium intake affect skin immune ractivity. in Svetski dan imunologije; 2018 Apr 26; Belgrade, Serbia. 2018;:24.
https://hdl.handle.net/21.15107/rcub_ibiss_4855 .

Mileusnić, Dina, Popov Aleksandrov, Aleksandra, Mirkov, Ivana, Ninkov, Marina, Kulaš, Jelena, Vukojević, Vesna, Đurđić, Slađana, Mutić, Jelena, Kataranovski, Milena, "Oral cadmium intake affect skin immune ractivity" in Svetski dan imunologije; 2018 Apr 26; Belgrade, Serbia (2018):24,
https://hdl.handle.net/21.15107/rcub_ibiss_4855 .

TY  - JOUR
AU  - Popov Aleksandrov, Aleksandra
AU  - Mirkov, Ivana
AU  - Ninkov, Marina
AU  - Tucović, Dina
AU  - Demenesku, Jelena
AU  - Subota, Vesna
AU  - Kataranovski, Dragan
AU  - Kataranovski, Milena
PY  - 2018
UR  - https://www.sciencedirect.com/science/article/pii/S027869151830019X?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2999
AB  - Warfarin is the world's most widely used anticoagulant drug. Its anticoagulant activity is based on the inhibition of the vitamin K-dependent (VKD) step in the complete synthesis of a number of blood coagulation factors that are required for normal blood coagulation. Warfarin also affects synthesis of VKD proteins not related to haemostasis including those involved in bone growth and vascular calcification. Antithrombotic activity of warfarin is considered responsible for some aspects of its anti-tumour activity of warfarin. Some aspects of activities against tumours seem not to be related to haemostasis and included effects of warfarin on non-haemostatic VKD proteins as well as those not related to VKD proteins. Inflammatory/immunomodulatory effects of warfarin indicate much broader potential of action of this drug both in physiological and pathological processes. This review provides an overview of the published data dealing with the effects of warfarin on biological processes other than haemostasis.
PB  - Pergamon
T2  - Food and Chemical Toxicology
T1  - Effects of warfarin on biological processes other than haemostasis: A review.
VL  - 113
DO  - 10.1016/j.fct.2018.01.019
SP  - 19
EP  - 32
ER  - 

@article{
author = "Popov Aleksandrov, Aleksandra and Mirkov, Ivana and Ninkov, Marina and Tucović, Dina and Demenesku, Jelena and Subota, Vesna and Kataranovski, Dragan and Kataranovski, Milena",
year = "2018",
abstract = "Warfarin is the world's most widely used anticoagulant drug. Its anticoagulant activity is based on the inhibition of the vitamin K-dependent (VKD) step in the complete synthesis of a number of blood coagulation factors that are required for normal blood coagulation. Warfarin also affects synthesis of VKD proteins not related to haemostasis including those involved in bone growth and vascular calcification. Antithrombotic activity of warfarin is considered responsible for some aspects of its anti-tumour activity of warfarin. Some aspects of activities against tumours seem not to be related to haemostasis and included effects of warfarin on non-haemostatic VKD proteins as well as those not related to VKD proteins. Inflammatory/immunomodulatory effects of warfarin indicate much broader potential of action of this drug both in physiological and pathological processes. This review provides an overview of the published data dealing with the effects of warfarin on biological processes other than haemostasis.",
publisher = "Pergamon",
journal = "Food and Chemical Toxicology",
title = "Effects of warfarin on biological processes other than haemostasis: A review.",
volume = "113",
doi = "10.1016/j.fct.2018.01.019",
pages = "19-32"
}

Popov Aleksandrov, A., Mirkov, I., Ninkov, M., Tucović, D., Demenesku, J., Subota, V., Kataranovski, D.,& Kataranovski, M.. (2018). Effects of warfarin on biological processes other than haemostasis: A review.. in Food and Chemical Toxicology
Pergamon., 113, 19-32.
https://doi.org/10.1016/j.fct.2018.01.019

Popov Aleksandrov A, Mirkov I, Ninkov M, Tucović D, Demenesku J, Subota V, Kataranovski D, Kataranovski M. Effects of warfarin on biological processes other than haemostasis: A review.. in Food and Chemical Toxicology. 2018;113:19-32.
doi:10.1016/j.fct.2018.01.019 .

Popov Aleksandrov, Aleksandra, Mirkov, Ivana, Ninkov, Marina, Tucović, Dina, Demenesku, Jelena, Subota, Vesna, Kataranovski, Dragan, Kataranovski, Milena, "Effects of warfarin on biological processes other than haemostasis: A review." in Food and Chemical Toxicology, 113 (2018):19-32,
https://doi.org/10.1016/j.fct.2018.01.019 . .

TY  - JOUR
AU  - Tucović, Dina
AU  - Popov Aleksandrov, Aleksandra
AU  - Mirkov, Ivana
AU  - Ninkov, Marina
AU  - Kulaš, Jelena
AU  - Zolotarevski, Lidija
AU  - Vukojević, Vesna
AU  - Mutić, Jelena
AU  - Tatalović, Nikola
AU  - Kataranovski, Milena
PY  - 2018
UR  - https://www.sciencedirect.com/science/article/pii/S0147651318307231?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3126
AB  - Skin can acquire cadmium (Cd) by oral route, but there is paucity of data concerning cutaneous effects of this metal. Cd acquired by oral route can affect skin wound healing, but the effect of Cd on other activities involved in skin homeostasis, including skin immunity, are not explored. Using the rat model of 30-day oral administration of Cd (5 ppm and 50 ppm) in drinking water, basic aspects of immune-relevant activity of epidermal cells were examined. Dose-dependent Cd deposition in the the skin was observed (0.035 ± 0.02 µg/g and 0.127 ± 0.04 µg/g at 5 ppm and 50 ppm, respectively, compared to 0.012 ± 0.009 µg/g at 0 ppm of Cd). This resulted in skin inflammation (oxidative stress at both Cd doses and dose-dependent structural changes in the skin and the presence/activation of innate immunity cells). At low Cd dose inflammatory response (nitric oxide and IL-1β) was observed. Other inflammatory cytokines (IL-6 and TNF) response occurred at 50 ppm, which was increased further following skin sensitization with contact allergen dinitro-chlorobenzene (DNCB). Epidermal cells exposed to both Cd doses enhanced concanavalin A (ConA)-stimulated lymphocyte production of IL-17. This study showed for the first time the effect of the metal which gained access to the skin via gut on immune reactivity of epidermal cells. Presented data might be relevant for the link between dietary Cd and the risk of skin pathologies.
T2  - Ecotoxicology and Environmental Safety
T1  - Oral cadmium exposure affects skin immune reactivity in rats.
VL  - 164
DO  - 10.1016/j.ecoenv.2018.07.117
SP  - 12
EP  - 20
ER  - 

@article{
author = "Tucović, Dina and Popov Aleksandrov, Aleksandra and Mirkov, Ivana and Ninkov, Marina and Kulaš, Jelena and Zolotarevski, Lidija and Vukojević, Vesna and Mutić, Jelena and Tatalović, Nikola and Kataranovski, Milena",
year = "2018",
abstract = "Skin can acquire cadmium (Cd) by oral route, but there is paucity of data concerning cutaneous effects of this metal. Cd acquired by oral route can affect skin wound healing, but the effect of Cd on other activities involved in skin homeostasis, including skin immunity, are not explored. Using the rat model of 30-day oral administration of Cd (5 ppm and 50 ppm) in drinking water, basic aspects of immune-relevant activity of epidermal cells were examined. Dose-dependent Cd deposition in the the skin was observed (0.035 ± 0.02 µg/g and 0.127 ± 0.04 µg/g at 5 ppm and 50 ppm, respectively, compared to 0.012 ± 0.009 µg/g at 0 ppm of Cd). This resulted in skin inflammation (oxidative stress at both Cd doses and dose-dependent structural changes in the skin and the presence/activation of innate immunity cells). At low Cd dose inflammatory response (nitric oxide and IL-1β) was observed. Other inflammatory cytokines (IL-6 and TNF) response occurred at 50 ppm, which was increased further following skin sensitization with contact allergen dinitro-chlorobenzene (DNCB). Epidermal cells exposed to both Cd doses enhanced concanavalin A (ConA)-stimulated lymphocyte production of IL-17. This study showed for the first time the effect of the metal which gained access to the skin via gut on immune reactivity of epidermal cells. Presented data might be relevant for the link between dietary Cd and the risk of skin pathologies.",
journal = "Ecotoxicology and Environmental Safety",
title = "Oral cadmium exposure affects skin immune reactivity in rats.",
volume = "164",
doi = "10.1016/j.ecoenv.2018.07.117",
pages = "12-20"
}

Tucović, D., Popov Aleksandrov, A., Mirkov, I., Ninkov, M., Kulaš, J., Zolotarevski, L., Vukojević, V., Mutić, J., Tatalović, N.,& Kataranovski, M.. (2018). Oral cadmium exposure affects skin immune reactivity in rats.. in Ecotoxicology and Environmental Safety, 164, 12-20.
https://doi.org/10.1016/j.ecoenv.2018.07.117

Tucović D, Popov Aleksandrov A, Mirkov I, Ninkov M, Kulaš J, Zolotarevski L, Vukojević V, Mutić J, Tatalović N, Kataranovski M. Oral cadmium exposure affects skin immune reactivity in rats.. in Ecotoxicology and Environmental Safety. 2018;164:12-20.
doi:10.1016/j.ecoenv.2018.07.117 .

Tucović, Dina, Popov Aleksandrov, Aleksandra, Mirkov, Ivana, Ninkov, Marina, Kulaš, Jelena, Zolotarevski, Lidija, Vukojević, Vesna, Mutić, Jelena, Tatalović, Nikola, Kataranovski, Milena, "Oral cadmium exposure affects skin immune reactivity in rats." in Ecotoxicology and Environmental Safety, 164 (2018):12-20,
https://doi.org/10.1016/j.ecoenv.2018.07.117 . .

TY  - JOUR
AU  - Janićijević, Željko
AU  - Ninkov, Marina
AU  - Kataranovski, Milena
AU  - Radovanović, Filip
PY  - 2018
UR  - https://onlinelibrary.wiley.com/doi/abs/10.1002/mabi.201800322
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3219
AB  - Poly(DL-lactide-co-ε-caprolactone)/poly(acrylic acid) implantable composite reservoirs for cationic drugs are synthesized by sequentially applying photoirradiation and liquid phase inversion. The chemical composition and microstructure of reservoirs are characterized with Fourier transform infrared spectroscopy-attenuated total reflection (FTIR-ATR) and scanning electron microscopy (SEM), respectively. Drug loading and release properties are investigated using methylene blue as the drug model. Biocompatibility of reservoirs is examined through a series of in vitro tests and an in vivo experiment of subcutaneous implantation in Dark Agouti rats. Reservoirs show good ion-exchange capacity, high water content, and fast reversible swelling with retained geometry. Results of drug loading and release reveal excellent loading efficiency and diffusion-controlled release during 2 weeks. Biocompatibility tests in vitro demonstrate the lack of implant proinflammatory potential and hindered adhesion of L929 cells on the implant surface. Implants exhibit low acute toxicity and elicit a normal acute foreign body reaction that reaches the early stages of fibrous capsule formation after 7 days.
T2  - Macromolecular Bioscience
T1  - Poly(DL-Lactide-co-ε-Caprolactone)/Poly(Acrylic Acid) Composite Implant for Controlled Delivery of Cationic Drugs.
DO  - 10.1002/mabi.201800322
ER  - 

@article{
author = "Janićijević, Željko and Ninkov, Marina and Kataranovski, Milena and Radovanović, Filip",
year = "2018",
abstract = "Poly(DL-lactide-co-ε-caprolactone)/poly(acrylic acid) implantable composite reservoirs for cationic drugs are synthesized by sequentially applying photoirradiation and liquid phase inversion. The chemical composition and microstructure of reservoirs are characterized with Fourier transform infrared spectroscopy-attenuated total reflection (FTIR-ATR) and scanning electron microscopy (SEM), respectively. Drug loading and release properties are investigated using methylene blue as the drug model. Biocompatibility of reservoirs is examined through a series of in vitro tests and an in vivo experiment of subcutaneous implantation in Dark Agouti rats. Reservoirs show good ion-exchange capacity, high water content, and fast reversible swelling with retained geometry. Results of drug loading and release reveal excellent loading efficiency and diffusion-controlled release during 2 weeks. Biocompatibility tests in vitro demonstrate the lack of implant proinflammatory potential and hindered adhesion of L929 cells on the implant surface. Implants exhibit low acute toxicity and elicit a normal acute foreign body reaction that reaches the early stages of fibrous capsule formation after 7 days.",
journal = "Macromolecular Bioscience",
title = "Poly(DL-Lactide-co-ε-Caprolactone)/Poly(Acrylic Acid) Composite Implant for Controlled Delivery of Cationic Drugs.",
doi = "10.1002/mabi.201800322"
}

Janićijević, Ž., Ninkov, M., Kataranovski, M.,& Radovanović, F.. (2018). Poly(DL-Lactide-co-ε-Caprolactone)/Poly(Acrylic Acid) Composite Implant for Controlled Delivery of Cationic Drugs.. in Macromolecular Bioscience.
https://doi.org/10.1002/mabi.201800322

Janićijević Ž, Ninkov M, Kataranovski M, Radovanović F. Poly(DL-Lactide-co-ε-Caprolactone)/Poly(Acrylic Acid) Composite Implant for Controlled Delivery of Cationic Drugs.. in Macromolecular Bioscience. 2018;.
doi:10.1002/mabi.201800322 .

Janićijević, Željko, Ninkov, Marina, Kataranovski, Milena, Radovanović, Filip, "Poly(DL-Lactide-co-ε-Caprolactone)/Poly(Acrylic Acid) Composite Implant for Controlled Delivery of Cationic Drugs." in Macromolecular Bioscience (2018),
https://doi.org/10.1002/mabi.201800322 . .

TY  - CONF
AU  - Mirkov, Ivana
AU  - Popov Aleksandrov, Aleksandra
AU  - Ninkov, Marina
AU  - Mileusnić, Dina
AU  - Kulaš, Jelena
AU  - Jovčić, Jelena
AU  - Stefanović, Jana
AU  - Glamočlija, Jasmina
AU  - Veljović, Katarina
AU  - Kataranovski, Milena
PY  - 2017
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4856
AB  - Our previous studies have shown poorer activity / absence of cellular immune response in AO compared to DA rats. Given the scarcity of data on innate immunity reactions in these two strains, the aim of this study was to obtain initial data on this type of immune activity. Using a model of subcutaneously implanted polyvinyl sponges, the basic aspects of neutrophil leukocyte activity important for the response to A. fumigatus were examined.Although a higher number of neutrophil leukocytes of AO rats migrate to fungal-free sponges (group K), the yield of cells from fungal sponges (group A) is the same in both strains, while CD11b cell expression is lower in both AO groups compared to DA rats. . Despite the higher oxidative activity of cells from group AO compared to DA, NBT reduction is the same (spontaneous) or lower (after stimulation with PMA) in group A compared to K in AO, and the production of myeloperoxidase (MPO) and NO is lower .In DA rats, the presence of the fungus leads to an increase in the activity of A cells in relation to group K. Molecular identification of the bacterial composition of the lung microbiota under conditions of infection with A. fumigatus established the presence of Staphylococcus epidermidis and Veillonella cavie only in AO, and Streptococcus salivarius and Propionibacterium acne only in DA rats. The presence of different doses of S. epidermidis (SE) in the sponge with A led to inhibition of MPO production in both strains. Soybean differences were observed depending on the dose of SE and / or the test activity. The lowest dose leads to inhibition of NBT reduction in AO, but stimulation in DA, while higher doses of SE stimulate the response in both strains.The low concentration of the bacterium has no effect on the production of NO in AO, but higher doses stimulate it, in contrast to the inhibition in DA at all doses of SE. The presented results indicate the existence of strain differences in the innate-immune response of rats, as well as that they may depend on the type of activity examined.
PB  - Belgrade: Immunological Society of Serbia
C3  - Svetski dan imunologije; 2017 Apr 26; Belgrade, Serbia
T1  - Influence of strain on the innate-immune reactions in rats
T1  - Uticaj soja na urođeno-imunske reakcije pacova
SP  - 18
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4856
ER  - 

@conference{
author = "Mirkov, Ivana and Popov Aleksandrov, Aleksandra and Ninkov, Marina and Mileusnić, Dina and Kulaš, Jelena and Jovčić, Jelena and Stefanović, Jana and Glamočlija, Jasmina and Veljović, Katarina and Kataranovski, Milena",
year = "2017",
abstract = "Our previous studies have shown poorer activity / absence of cellular immune response in AO compared to DA rats. Given the scarcity of data on innate immunity reactions in these two strains, the aim of this study was to obtain initial data on this type of immune activity. Using a model of subcutaneously implanted polyvinyl sponges, the basic aspects of neutrophil leukocyte activity important for the response to A. fumigatus were examined.Although a higher number of neutrophil leukocytes of AO rats migrate to fungal-free sponges (group K), the yield of cells from fungal sponges (group A) is the same in both strains, while CD11b cell expression is lower in both AO groups compared to DA rats. . Despite the higher oxidative activity of cells from group AO compared to DA, NBT reduction is the same (spontaneous) or lower (after stimulation with PMA) in group A compared to K in AO, and the production of myeloperoxidase (MPO) and NO is lower .In DA rats, the presence of the fungus leads to an increase in the activity of A cells in relation to group K. Molecular identification of the bacterial composition of the lung microbiota under conditions of infection with A. fumigatus established the presence of Staphylococcus epidermidis and Veillonella cavie only in AO, and Streptococcus salivarius and Propionibacterium acne only in DA rats. The presence of different doses of S. epidermidis (SE) in the sponge with A led to inhibition of MPO production in both strains. Soybean differences were observed depending on the dose of SE and / or the test activity. The lowest dose leads to inhibition of NBT reduction in AO, but stimulation in DA, while higher doses of SE stimulate the response in both strains.The low concentration of the bacterium has no effect on the production of NO in AO, but higher doses stimulate it, in contrast to the inhibition in DA at all doses of SE. The presented results indicate the existence of strain differences in the innate-immune response of rats, as well as that they may depend on the type of activity examined.",
publisher = "Belgrade: Immunological Society of Serbia",
journal = "Svetski dan imunologije; 2017 Apr 26; Belgrade, Serbia",
title = "Influence of strain on the innate-immune reactions in rats, Uticaj soja na urođeno-imunske reakcije pacova",
pages = "18",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4856"
}

Mirkov, I., Popov Aleksandrov, A., Ninkov, M., Mileusnić, D., Kulaš, J., Jovčić, J., Stefanović, J., Glamočlija, J., Veljović, K.,& Kataranovski, M.. (2017). Influence of strain on the innate-immune reactions in rats. in Svetski dan imunologije; 2017 Apr 26; Belgrade, Serbia
Belgrade: Immunological Society of Serbia., 18.
https://hdl.handle.net/21.15107/rcub_ibiss_4856

Mirkov I, Popov Aleksandrov A, Ninkov M, Mileusnić D, Kulaš J, Jovčić J, Stefanović J, Glamočlija J, Veljović K, Kataranovski M. Influence of strain on the innate-immune reactions in rats. in Svetski dan imunologije; 2017 Apr 26; Belgrade, Serbia. 2017;:18.
https://hdl.handle.net/21.15107/rcub_ibiss_4856 .

Mirkov, Ivana, Popov Aleksandrov, Aleksandra, Ninkov, Marina, Mileusnić, Dina, Kulaš, Jelena, Jovčić, Jelena, Stefanović, Jana, Glamočlija, Jasmina, Veljović, Katarina, Kataranovski, Milena, "Influence of strain on the innate-immune reactions in rats" in Svetski dan imunologije; 2017 Apr 26; Belgrade, Serbia (2017):18,
https://hdl.handle.net/21.15107/rcub_ibiss_4856 .

TY  - JOUR
AU  - Mirkov, Ivana
AU  - Popov Aleksandrov, Aleksandra
AU  - Demenesku, Jelena
AU  - Ninkov, Marina
AU  - Tucović, Dina
AU  - Kataranovski, Dragan
AU  - Kataranovski, Milena
PY  - 2017
UR  - https://www.tandfonline.com/doi/full/10.1080/15569527.2016.1275664
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2555
AB  - Purpose: Warfarin (WF) is an anticoagulant which also affects physiological processes other than hemostasis. Our previous investigations showed the effect of WF which gained access to the organism via skin on resting peripheral blood granulocytes. Based on these data, the aim of the present study was to examine whether WF could modulate the inflammatory processes as well. To this aim the effect of WF on the inflammatory response induced by subcutaneous sponge implantation in rats was examined. Materials and methods: Warfarin-soaked polyvinyl sponges (WF-sponges) were implanted subcutaneously and cell infiltration into sponges, the levels of nitric oxide (NO) and inflammatory cytokines tumor necrosis factor (TNF) and interleukin-6 (IL-6) production by sponge cells were measured as parameters of inflammation. T cell infiltration and cytokine interferon-γ (IFN-γ), interleukin-17 (IL-17) and interleukin-10 (IL-10) were measured at day 7 post implantation. Results: Warfarin exerted both stimulatory and suppressive effects depending on the parameter examined. Flow cytometry of cells recovered from sponges showed higher numbers of granulocytes (HIS48+ cells) at days 1 and 3 post implantation and CD11b+ cells at day 1 compared to control sponges. Cells from WF-sponges had an increased NO production (Griess reaction) at days 1 and 7. In contrast, lower levels of TNF (measured by ELISA) production by cells recovered from WF-soaked sponges were found in the early (day one) phase of reaction with unchanged levels at other time points. While IL-6 production by cells recovered from WF-soaked sponges was decreased at day 1, it was increased at day 7. Higher T cell numbers were noted in WF sponges at day 7 post implantation, and recovered cells produced more IFN-γ and IL-17, while IL-10 production remained unchanged. Conclusions: Warfarin affects some of the parameters of inflammatory reaction induced by subcutaneous polyvinyl sponge implantation. Differential (both stimulatory as well as inhibitory) effects of WF on inflammatory response to sponge implants might affect the course and/or duration of this reaction.
T2  - Cutaneous and Ocular Toxicology
T1  - Warfarin affects acute inflammatory response induced by subcutaneous polyvinyl sponge implantation in rats
DO  - 10.1080/15569527.2016.1275664
ER  - 

@article{
author = "Mirkov, Ivana and Popov Aleksandrov, Aleksandra and Demenesku, Jelena and Ninkov, Marina and Tucović, Dina and Kataranovski, Dragan and Kataranovski, Milena",
year = "2017",
abstract = "Purpose: Warfarin (WF) is an anticoagulant which also affects physiological processes other than hemostasis. Our previous investigations showed the effect of WF which gained access to the organism via skin on resting peripheral blood granulocytes. Based on these data, the aim of the present study was to examine whether WF could modulate the inflammatory processes as well. To this aim the effect of WF on the inflammatory response induced by subcutaneous sponge implantation in rats was examined. Materials and methods: Warfarin-soaked polyvinyl sponges (WF-sponges) were implanted subcutaneously and cell infiltration into sponges, the levels of nitric oxide (NO) and inflammatory cytokines tumor necrosis factor (TNF) and interleukin-6 (IL-6) production by sponge cells were measured as parameters of inflammation. T cell infiltration and cytokine interferon-γ (IFN-γ), interleukin-17 (IL-17) and interleukin-10 (IL-10) were measured at day 7 post implantation. Results: Warfarin exerted both stimulatory and suppressive effects depending on the parameter examined. Flow cytometry of cells recovered from sponges showed higher numbers of granulocytes (HIS48+ cells) at days 1 and 3 post implantation and CD11b+ cells at day 1 compared to control sponges. Cells from WF-sponges had an increased NO production (Griess reaction) at days 1 and 7. In contrast, lower levels of TNF (measured by ELISA) production by cells recovered from WF-soaked sponges were found in the early (day one) phase of reaction with unchanged levels at other time points. While IL-6 production by cells recovered from WF-soaked sponges was decreased at day 1, it was increased at day 7. Higher T cell numbers were noted in WF sponges at day 7 post implantation, and recovered cells produced more IFN-γ and IL-17, while IL-10 production remained unchanged. Conclusions: Warfarin affects some of the parameters of inflammatory reaction induced by subcutaneous polyvinyl sponge implantation. Differential (both stimulatory as well as inhibitory) effects of WF on inflammatory response to sponge implants might affect the course and/or duration of this reaction.",
journal = "Cutaneous and Ocular Toxicology",
title = "Warfarin affects acute inflammatory response induced by subcutaneous polyvinyl sponge implantation in rats",
doi = "10.1080/15569527.2016.1275664"
}

Mirkov, I., Popov Aleksandrov, A., Demenesku, J., Ninkov, M., Tucović, D., Kataranovski, D.,& Kataranovski, M.. (2017). Warfarin affects acute inflammatory response induced by subcutaneous polyvinyl sponge implantation in rats. in Cutaneous and Ocular Toxicology.
https://doi.org/10.1080/15569527.2016.1275664

Mirkov I, Popov Aleksandrov A, Demenesku J, Ninkov M, Tucović D, Kataranovski D, Kataranovski M. Warfarin affects acute inflammatory response induced by subcutaneous polyvinyl sponge implantation in rats. in Cutaneous and Ocular Toxicology. 2017;.
doi:10.1080/15569527.2016.1275664 .

Mirkov, Ivana, Popov Aleksandrov, Aleksandra, Demenesku, Jelena, Ninkov, Marina, Tucović, Dina, Kataranovski, Dragan, Kataranovski, Milena, "Warfarin affects acute inflammatory response induced by subcutaneous polyvinyl sponge implantation in rats" in Cutaneous and Ocular Toxicology (2017),
https://doi.org/10.1080/15569527.2016.1275664 . .

TY  - JOUR
AU  - Popov Aleksandrov, Aleksandra
AU  - Mirkov, Ivana
AU  - Zolotarevski, Lidija
AU  - Ninkov, Marina
AU  - Tucović, Dina
AU  - Kataranovski, Dragan
AU  - Kataranovski, Milena
PY  - 2017
UR  - https://www.sciencedirect.com/science/article/pii/S1382668917301746?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3540
AB  - Warfarin is an anticoagulant used in prevention/prophylaxis of thromboembolism. Besides the effects on coagulation, non-hemorrhagic reactions have also been documented. Although cutaneous reactions were reported in some patients, the impact on skin immunity was not explored. In the present paper, the effect of 30-day oral warfarin intake on skin cytokine responses in rats was analyzed. Increased release of inflammatory cytokines (TNF, IL-1β and IL-10) was noted by skin explants from rats which received warfarin, but without effect on IL-6. No impact on epidermal cell cytokine secretion was seen, except a tendency of an increase of IL-6 response to stimulation with microbial product lipopolysaccharide (LPS). Topical application of contact allergen dinitrochlorobenzene (DNCB) resulted in slight (numerical solely) increase of TNF release by skin explants of warfarin-treated animals, while epidermal cells responded by increased secretion of all four cytokines examined. The data presented provide new information on the potential of oral warfarin to modulate skin innate immune activity.
T2  - Environmental Toxicology and Pharmacology
T1  - Oral warfarin intake affects skin inflammatory cytokine responses in rats.
VL  - 54
DO  - 10.1016/j.etap.2017.06.027
SP  - 93
EP  - 98
ER  - 

@article{
author = "Popov Aleksandrov, Aleksandra and Mirkov, Ivana and Zolotarevski, Lidija and Ninkov, Marina and Tucović, Dina and Kataranovski, Dragan and Kataranovski, Milena",
year = "2017",
abstract = "Warfarin is an anticoagulant used in prevention/prophylaxis of thromboembolism. Besides the effects on coagulation, non-hemorrhagic reactions have also been documented. Although cutaneous reactions were reported in some patients, the impact on skin immunity was not explored. In the present paper, the effect of 30-day oral warfarin intake on skin cytokine responses in rats was analyzed. Increased release of inflammatory cytokines (TNF, IL-1β and IL-10) was noted by skin explants from rats which received warfarin, but without effect on IL-6. No impact on epidermal cell cytokine secretion was seen, except a tendency of an increase of IL-6 response to stimulation with microbial product lipopolysaccharide (LPS). Topical application of contact allergen dinitrochlorobenzene (DNCB) resulted in slight (numerical solely) increase of TNF release by skin explants of warfarin-treated animals, while epidermal cells responded by increased secretion of all four cytokines examined. The data presented provide new information on the potential of oral warfarin to modulate skin innate immune activity.",
journal = "Environmental Toxicology and Pharmacology",
title = "Oral warfarin intake affects skin inflammatory cytokine responses in rats.",
volume = "54",
doi = "10.1016/j.etap.2017.06.027",
pages = "93-98"
}

Popov Aleksandrov, A., Mirkov, I., Zolotarevski, L., Ninkov, M., Tucović, D., Kataranovski, D.,& Kataranovski, M.. (2017). Oral warfarin intake affects skin inflammatory cytokine responses in rats.. in Environmental Toxicology and Pharmacology, 54, 93-98.
https://doi.org/10.1016/j.etap.2017.06.027

Popov Aleksandrov A, Mirkov I, Zolotarevski L, Ninkov M, Tucović D, Kataranovski D, Kataranovski M. Oral warfarin intake affects skin inflammatory cytokine responses in rats.. in Environmental Toxicology and Pharmacology. 2017;54:93-98.
doi:10.1016/j.etap.2017.06.027 .

Popov Aleksandrov, Aleksandra, Mirkov, Ivana, Zolotarevski, Lidija, Ninkov, Marina, Tucović, Dina, Kataranovski, Dragan, Kataranovski, Milena, "Oral warfarin intake affects skin inflammatory cytokine responses in rats." in Environmental Toxicology and Pharmacology, 54 (2017):93-98,
https://doi.org/10.1016/j.etap.2017.06.027 . .

TY  - JOUR
AU  - Mirkov, Ivana
AU  - Popov Aleksandrov, Aleksandra
AU  - Ninkov, Marina
AU  - Mileusnić, Dina
AU  - Demenesku, Jelena
AU  - Zolotarevski, Lidija
AU  - Subota, Vesna
AU  - Stefik, Debora
AU  - Kataranovski, Dragan
AU  - Kataranovski, Milena
PY  - 2016
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4813
AB  - Intestinal hemorrhage characterizes effectiveness of warfarin (WF) as rodenticide and is amongadverse effects of therapy in humans. Having in mind genetic variations in the effectiveness ofWF in wild rats and in the doses required for therapeutic effect, strain differences in the intestinaltoxicity of oral warfarin in rats were examined in this study. High WF dose (3.5 mg/l) led tomortality in Albino Oxford (AO) rats, with no lethality in Dark Agouti (DA) rats. Higher valuesof prothrombin time were noted at low WF dose (0.35 mg/l) in the former strain. Leukocyteinfiltration in intestine noted at this dose in both strains was associated with oxidative injury andmore pronounced anti-oxidative response in AO rats. Suppression of mesenteric lymph node cellproliferation and IFN-γ and IL-10 production in AO rats and lack of these effects in DA rats,represent different strategies to protect vulnerable intestine from harmful immune responses.
PB  - Amsterdam, Holland:Elsevier B.V.
T2  - Environmental Toxicology and Pharmacology
T1  - Strain differences in intestinal toxicity of warfarin in rats
VL  - 48
DO  - 10.1016/j.etap.2016.10.019
SP  - 175
EP  - 182
ER  - 

@article{
author = "Mirkov, Ivana and Popov Aleksandrov, Aleksandra and Ninkov, Marina and Mileusnić, Dina and Demenesku, Jelena and Zolotarevski, Lidija and Subota, Vesna and Stefik, Debora and Kataranovski, Dragan and Kataranovski, Milena",
year = "2016",
abstract = "Intestinal hemorrhage characterizes effectiveness of warfarin (WF) as rodenticide and is amongadverse effects of therapy in humans. Having in mind genetic variations in the effectiveness ofWF in wild rats and in the doses required for therapeutic effect, strain differences in the intestinaltoxicity of oral warfarin in rats were examined in this study. High WF dose (3.5 mg/l) led tomortality in Albino Oxford (AO) rats, with no lethality in Dark Agouti (DA) rats. Higher valuesof prothrombin time were noted at low WF dose (0.35 mg/l) in the former strain. Leukocyteinfiltration in intestine noted at this dose in both strains was associated with oxidative injury andmore pronounced anti-oxidative response in AO rats. Suppression of mesenteric lymph node cellproliferation and IFN-γ and IL-10 production in AO rats and lack of these effects in DA rats,represent different strategies to protect vulnerable intestine from harmful immune responses.",
publisher = "Amsterdam, Holland:Elsevier B.V.",
journal = "Environmental Toxicology and Pharmacology",
title = "Strain differences in intestinal toxicity of warfarin in rats",
volume = "48",
doi = "10.1016/j.etap.2016.10.019",
pages = "175-182"
}

Mirkov, I., Popov Aleksandrov, A., Ninkov, M., Mileusnić, D., Demenesku, J., Zolotarevski, L., Subota, V., Stefik, D., Kataranovski, D.,& Kataranovski, M.. (2016). Strain differences in intestinal toxicity of warfarin in rats. in Environmental Toxicology and Pharmacology
Amsterdam, Holland:Elsevier B.V.., 48, 175-182.
https://doi.org/10.1016/j.etap.2016.10.019

Mirkov I, Popov Aleksandrov A, Ninkov M, Mileusnić D, Demenesku J, Zolotarevski L, Subota V, Stefik D, Kataranovski D, Kataranovski M. Strain differences in intestinal toxicity of warfarin in rats. in Environmental Toxicology and Pharmacology. 2016;48:175-182.
doi:10.1016/j.etap.2016.10.019 .

Mirkov, Ivana, Popov Aleksandrov, Aleksandra, Ninkov, Marina, Mileusnić, Dina, Demenesku, Jelena, Zolotarevski, Lidija, Subota, Vesna, Stefik, Debora, Kataranovski, Dragan, Kataranovski, Milena, "Strain differences in intestinal toxicity of warfarin in rats" in Environmental Toxicology and Pharmacology, 48 (2016):175-182,
https://doi.org/10.1016/j.etap.2016.10.019 . .

TY  - JOUR
AU  - Mirkov, Ivana
AU  - Popov Aleksandrov, Aleksandra
AU  - Ninkov, Marina
AU  - Mileusnić, Dina
AU  - Demenesku, Jelena
AU  - Zolotarevski, Lidija
AU  - Subota, Vesna
AU  - Stefik, Debora
AU  - Kataranovski, Dragan
AU  - Kataranovski, Milena
PY  - 2016
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4812
AB  - Intestinal hemorrhage characterizes effectiveness of warfarin (WF) as rodenticide and is among
adverse effects of therapy in humans. Having in mind genetic variations in the effectiveness of
WF in wild rats and in the doses required for therapeutic effect, strain differences in the intestinal
toxicity of oral warfarin in rats were examined in this study. High WF dose (3.5 mg/l) led to
mortality in Albino Oxford (AO) rats, with no lethality in Dark Agouti (DA) rats. Higher values
of prothrombin time were noted at low WF dose (0.35 mg/l) in the former strain. Leukocyte
infiltration in intestine noted at this dose in both strains was associated with oxidative injury and
more pronounced anti-oxidative response in AO rats. Suppression of mesenteric lymph node cell
proliferation and IFN-γ and IL-10 production in AO rats and lack of these effects in DA rats,
represent different strategies to protect vulnerable intestine from harmful immune responses.
PB  - Amsterdam, Holland:Elsevier B.V.
T2  - Environmental Toxicology and Pharmacology
T1  - Strain differences in intestinal toxicity of warfarin in rats
VL  - 48
DO  - 10.1016/j.etap.2016.10.019
SP  - 175
EP  - 182
ER  - 

@article{
author = "Mirkov, Ivana and Popov Aleksandrov, Aleksandra and Ninkov, Marina and Mileusnić, Dina and Demenesku, Jelena and Zolotarevski, Lidija and Subota, Vesna and Stefik, Debora and Kataranovski, Dragan and Kataranovski, Milena",
year = "2016",
abstract = "Intestinal hemorrhage characterizes effectiveness of warfarin (WF) as rodenticide and is among
adverse effects of therapy in humans. Having in mind genetic variations in the effectiveness of
WF in wild rats and in the doses required for therapeutic effect, strain differences in the intestinal
toxicity of oral warfarin in rats were examined in this study. High WF dose (3.5 mg/l) led to
mortality in Albino Oxford (AO) rats, with no lethality in Dark Agouti (DA) rats. Higher values
of prothrombin time were noted at low WF dose (0.35 mg/l) in the former strain. Leukocyte
infiltration in intestine noted at this dose in both strains was associated with oxidative injury and
more pronounced anti-oxidative response in AO rats. Suppression of mesenteric lymph node cell
proliferation and IFN-γ and IL-10 production in AO rats and lack of these effects in DA rats,
represent different strategies to protect vulnerable intestine from harmful immune responses.",
publisher = "Amsterdam, Holland:Elsevier B.V.",
journal = "Environmental Toxicology and Pharmacology",
title = "Strain differences in intestinal toxicity of warfarin in rats",
volume = "48",
doi = "10.1016/j.etap.2016.10.019",
pages = "175-182"
}

Mirkov, I., Popov Aleksandrov, A., Ninkov, M., Mileusnić, D., Demenesku, J., Zolotarevski, L., Subota, V., Stefik, D., Kataranovski, D.,& Kataranovski, M.. (2016). Strain differences in intestinal toxicity of warfarin in rats. in Environmental Toxicology and Pharmacology
Amsterdam, Holland:Elsevier B.V.., 48, 175-182.
https://doi.org/10.1016/j.etap.2016.10.019

Mirkov I, Popov Aleksandrov A, Ninkov M, Mileusnić D, Demenesku J, Zolotarevski L, Subota V, Stefik D, Kataranovski D, Kataranovski M. Strain differences in intestinal toxicity of warfarin in rats. in Environmental Toxicology and Pharmacology. 2016;48:175-182.
doi:10.1016/j.etap.2016.10.019 .

Mirkov, Ivana, Popov Aleksandrov, Aleksandra, Ninkov, Marina, Mileusnić, Dina, Demenesku, Jelena, Zolotarevski, Lidija, Subota, Vesna, Stefik, Debora, Kataranovski, Dragan, Kataranovski, Milena, "Strain differences in intestinal toxicity of warfarin in rats" in Environmental Toxicology and Pharmacology, 48 (2016):175-182,
https://doi.org/10.1016/j.etap.2016.10.019 . .

TY  - JOUR
AU  - Subota, Vesna
AU  - Mirkov, Ivana
AU  - Demenesku, Jelena
AU  - Popov Aleksandrov, Aleksandra
AU  - Ninkov, Marina
AU  - Mileusnić, Dina
AU  - Kataranovski, Dragan
AU  - Kataranovski, Milena
PY  - 2016
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4814
AB  - Occupational/accidental exposure data have showed hemorrhage as a result of transdermal exposure to
warfarin, however, other effects are not known. In the present study, the impact of epicutaneous application of 10 g or 100 g of warfarin (three times, once a day) on peripheral blood polymorphonuclear
(PMN) and mononuclear cells (PBMC) was examined in rats. Both doses resulted in prolongation of prothrombin time and changes in hematologic parameters. Increases in PMN intracellular myeloperoxidase
(MPO) activity were seen at higher warfarin dose and both doses resulted in higher percentages of granular CD11b+ cells. In contrast, a decrease in PMN TNF and IL-6 production (ELISA) and gene expression
(RT-PCR) was observed. Epicutaneous application of warfarin resulted in decreased numbers of PBMC,
higher numbers of mononuclear CD11b+ cells, but without effect on PMBC cytokine production. The data
obtained showed differential effects of transdermal exposure to warfarin depending on leukocyte type
and activity.
PB  - Amsterdam : Elsevier
T2  - Environmental Toxicology and Pharmacology
T1  - Transdermal toxicity of topically applied anticoagulant rodenticide warfarin in rats
VL  - 41
DO  - 10.1016/j.etap.2015.12.006
SP  - 232
EP  - 240
ER  - 

@article{
author = "Subota, Vesna and Mirkov, Ivana and Demenesku, Jelena and Popov Aleksandrov, Aleksandra and Ninkov, Marina and Mileusnić, Dina and Kataranovski, Dragan and Kataranovski, Milena",
year = "2016",
abstract = "Occupational/accidental exposure data have showed hemorrhage as a result of transdermal exposure to
warfarin, however, other effects are not known. In the present study, the impact of epicutaneous application of 10 g or 100 g of warfarin (three times, once a day) on peripheral blood polymorphonuclear
(PMN) and mononuclear cells (PBMC) was examined in rats. Both doses resulted in prolongation of prothrombin time and changes in hematologic parameters. Increases in PMN intracellular myeloperoxidase
(MPO) activity were seen at higher warfarin dose and both doses resulted in higher percentages of granular CD11b+ cells. In contrast, a decrease in PMN TNF and IL-6 production (ELISA) and gene expression
(RT-PCR) was observed. Epicutaneous application of warfarin resulted in decreased numbers of PBMC,
higher numbers of mononuclear CD11b+ cells, but without effect on PMBC cytokine production. The data
obtained showed differential effects of transdermal exposure to warfarin depending on leukocyte type
and activity.",
publisher = "Amsterdam : Elsevier",
journal = "Environmental Toxicology and Pharmacology",
title = "Transdermal toxicity of topically applied anticoagulant rodenticide warfarin in rats",
volume = "41",
doi = "10.1016/j.etap.2015.12.006",
pages = "232-240"
}

Subota, V., Mirkov, I., Demenesku, J., Popov Aleksandrov, A., Ninkov, M., Mileusnić, D., Kataranovski, D.,& Kataranovski, M.. (2016). Transdermal toxicity of topically applied anticoagulant rodenticide warfarin in rats. in Environmental Toxicology and Pharmacology
Amsterdam : Elsevier., 41, 232-240.
https://doi.org/10.1016/j.etap.2015.12.006

Subota V, Mirkov I, Demenesku J, Popov Aleksandrov A, Ninkov M, Mileusnić D, Kataranovski D, Kataranovski M. Transdermal toxicity of topically applied anticoagulant rodenticide warfarin in rats. in Environmental Toxicology and Pharmacology. 2016;41:232-240.
doi:10.1016/j.etap.2015.12.006 .

Subota, Vesna, Mirkov, Ivana, Demenesku, Jelena, Popov Aleksandrov, Aleksandra, Ninkov, Marina, Mileusnić, Dina, Kataranovski, Dragan, Kataranovski, Milena, "Transdermal toxicity of topically applied anticoagulant rodenticide warfarin in rats" in Environmental Toxicology and Pharmacology, 41 (2016):232-240,
https://doi.org/10.1016/j.etap.2015.12.006 . .

TY  - JOUR
AU  - Mirkov, Ivana
AU  - Popov Aleksandrov, Aleksandra
AU  - Demenesku, Jelena
AU  - Ninkov, Marina
AU  - Mileusnić, Dina
AU  - Zolotarevski, Lidija
AU  - Subota, Vesna
AU  - Kataranovski, Dragan
AU  - Kataranovski, Milena
PY  - 2016
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4815
AB  - Though warfarin is extensively used in the prevention and treatment of thromboembolic
processes in humans, adverse effects of warfarin therapy have been recognized. Intestinal
hemorrhage is one of the hazards of anticoagulant therapy, but the mechanisms of warfarin
toxicity are virtually unknown. In this work, the effects of 30 days oral warfarin (0.35 mg/l and
3.5 mg/l) intake on rat’s gut were examined. Both doses resulted in prolongation of prothrombin
time. Systemic effects of higher warfarin dose (increases in plasma AST, proteinuria, hematuria,
changes in peripheral blood hematological parameters) were seen. Warfarin intake resulted in
histologically evident tissue damage, leukocyte infiltration and intestinal inflammation [increases
in myeloperoxidase activity, malondialdehyde content, superoxide dismutase and catalase
activity, proinflammatory cytokine (IFN-γ, IL-17) concentrations in intestinal homogenates]. In
contrast, suppression of gut-draining mesenteric lymph node (MLN) cell activity [proliferation
responsiveness, production of IFN-γ and IL-17 to T lymphocyte mitogen Concanavalin A
stimulation] was noted. Inhibition of regulatory cytokine IL-10 production by MLN cells,
suggests commitment of MLN to the suppression of all inflammatory activities and creation of
the microenvironment which is non-permissive for induction of potentially harmful immune
response. These novel findings indicate the need of staying alert for (adverse) effects of warfarin
therapy.
PB  - Amsterdam : Elsevier
T2  - Food and Chemical Toxicology
T1  - Intestinal toxicity of oral warfarin intake in rats
VL  - 94
DO  - 10.1016/j.fct.2016.05.007
SP  - 11
EP  - 18
ER  - 

@article{
author = "Mirkov, Ivana and Popov Aleksandrov, Aleksandra and Demenesku, Jelena and Ninkov, Marina and Mileusnić, Dina and Zolotarevski, Lidija and Subota, Vesna and Kataranovski, Dragan and Kataranovski, Milena",
year = "2016",
abstract = "Though warfarin is extensively used in the prevention and treatment of thromboembolic
processes in humans, adverse effects of warfarin therapy have been recognized. Intestinal
hemorrhage is one of the hazards of anticoagulant therapy, but the mechanisms of warfarin
toxicity are virtually unknown. In this work, the effects of 30 days oral warfarin (0.35 mg/l and
3.5 mg/l) intake on rat’s gut were examined. Both doses resulted in prolongation of prothrombin
time. Systemic effects of higher warfarin dose (increases in plasma AST, proteinuria, hematuria,
changes in peripheral blood hematological parameters) were seen. Warfarin intake resulted in
histologically evident tissue damage, leukocyte infiltration and intestinal inflammation [increases
in myeloperoxidase activity, malondialdehyde content, superoxide dismutase and catalase
activity, proinflammatory cytokine (IFN-γ, IL-17) concentrations in intestinal homogenates]. In
contrast, suppression of gut-draining mesenteric lymph node (MLN) cell activity [proliferation
responsiveness, production of IFN-γ and IL-17 to T lymphocyte mitogen Concanavalin A
stimulation] was noted. Inhibition of regulatory cytokine IL-10 production by MLN cells,
suggests commitment of MLN to the suppression of all inflammatory activities and creation of
the microenvironment which is non-permissive for induction of potentially harmful immune
response. These novel findings indicate the need of staying alert for (adverse) effects of warfarin
therapy.",
publisher = "Amsterdam : Elsevier",
journal = "Food and Chemical Toxicology",
title = "Intestinal toxicity of oral warfarin intake in rats",
volume = "94",
doi = "10.1016/j.fct.2016.05.007",
pages = "11-18"
}

Mirkov, I., Popov Aleksandrov, A., Demenesku, J., Ninkov, M., Mileusnić, D., Zolotarevski, L., Subota, V., Kataranovski, D.,& Kataranovski, M.. (2016). Intestinal toxicity of oral warfarin intake in rats. in Food and Chemical Toxicology
Amsterdam : Elsevier., 94, 11-18.
https://doi.org/10.1016/j.fct.2016.05.007

Mirkov I, Popov Aleksandrov A, Demenesku J, Ninkov M, Mileusnić D, Zolotarevski L, Subota V, Kataranovski D, Kataranovski M. Intestinal toxicity of oral warfarin intake in rats. in Food and Chemical Toxicology. 2016;94:11-18.
doi:10.1016/j.fct.2016.05.007 .

Mirkov, Ivana, Popov Aleksandrov, Aleksandra, Demenesku, Jelena, Ninkov, Marina, Mileusnić, Dina, Zolotarevski, Lidija, Subota, Vesna, Kataranovski, Dragan, Kataranovski, Milena, "Intestinal toxicity of oral warfarin intake in rats" in Food and Chemical Toxicology, 94 (2016):11-18,
https://doi.org/10.1016/j.fct.2016.05.007 . .

TY  - CONF
AU  - Ninkov, Marina
AU  - Popov Aleksandrov, Aleksandra
AU  - Mirkov, Ivana
AU  - Demenesku, Jelena
AU  - Brceski, Ilija
AU  - Tolinacki, Maja
AU  - Jovanovic, Sofija
AU  - Mileusnić, Dina
AU  - Kataranovski, Dragan
AU  - Kataranovski, Milena
PY  - 2016
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4854
AB  - Our previous research showed a higher reactivity of DA (compared to AO rats) to antigens that cause skin and lung inflammatory reactions. In order to examine the effect of strains on the immune responses of other regions, the effect of oral (in drinking water, 30 days) intake of cadmium, a known food and water contaminant, on the intestinal immune response of AO and DA rats was analyzed. Despite similar amounts of cadmium deposited in the intestines of both strains, the reduction in Lactobacillus (important for maintaining immune homeostasis in the intestine) and tissue damage (histologically and according to the marker of tissue necrosis, HMGB-1) was more pronounced in DA rats.Changes, including the activity of antioxidant defense enzymes (superoxide dismutase and catalase), increased concentrations of IFN-γ and IL-17, and no changes in IL-10, which were detected in intestinal homogenates only in DA strains, indicate a more intense intestinal inflammatory reaction. compared to AO strain. The same concentrations of cadmium detected in the main draining (mesenteric) lymph nodes (MLC) led to the induction of mRNA for metal-binding redox proteins (metallothioneins, MT) only in DA rats. The presence of a proinflammatory cytokine response (protein products and mRNA) of MLC cells, detected predominantly in DA strains, indicates a more pronounced induction of cells that produce these cytokines.Increased cell proliferation and oxidative activity of MLC cells, as well as the number of CD68 +, NKG2D + and CD11b + cells only in DA rats, with a differential change in IL-10 (decrease in DA, increase in AO) emphasizes the inflammatory character of MLC rat microenvironment of this strain. The absence of similar changes in the spleen (at the same tissue load of cadmium as MLC) indicates the influence of damaged intestinal tissue on the activity of regional lymph nodes, and the more intense response of MLC DA soy reflects greater efforts to prevent systemic immune response to changes in intestinal homeostasis.
PB  - Belgrade: Immunological Society of Serbia
C3  - VII Naučni sastanak Društva imunologa Srbije, Belgrade, Serbia, 27-28 april 2016, Knjiga apstrakata
T1  - Differential strain impact on immune reactivity: insights from regional immune responses in rats
T1  - Diferencijalni uticaj soja na imunsku reaktivnost: uvid iz regionalnih imunskih odgovora kod pacova
SP  - 10
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4854
ER  - 

@conference{
author = "Ninkov, Marina and Popov Aleksandrov, Aleksandra and Mirkov, Ivana and Demenesku, Jelena and Brceski, Ilija and Tolinacki, Maja and Jovanovic, Sofija and Mileusnić, Dina and Kataranovski, Dragan and Kataranovski, Milena",
year = "2016",
abstract = "Our previous research showed a higher reactivity of DA (compared to AO rats) to antigens that cause skin and lung inflammatory reactions. In order to examine the effect of strains on the immune responses of other regions, the effect of oral (in drinking water, 30 days) intake of cadmium, a known food and water contaminant, on the intestinal immune response of AO and DA rats was analyzed. Despite similar amounts of cadmium deposited in the intestines of both strains, the reduction in Lactobacillus (important for maintaining immune homeostasis in the intestine) and tissue damage (histologically and according to the marker of tissue necrosis, HMGB-1) was more pronounced in DA rats.Changes, including the activity of antioxidant defense enzymes (superoxide dismutase and catalase), increased concentrations of IFN-γ and IL-17, and no changes in IL-10, which were detected in intestinal homogenates only in DA strains, indicate a more intense intestinal inflammatory reaction. compared to AO strain. The same concentrations of cadmium detected in the main draining (mesenteric) lymph nodes (MLC) led to the induction of mRNA for metal-binding redox proteins (metallothioneins, MT) only in DA rats. The presence of a proinflammatory cytokine response (protein products and mRNA) of MLC cells, detected predominantly in DA strains, indicates a more pronounced induction of cells that produce these cytokines.Increased cell proliferation and oxidative activity of MLC cells, as well as the number of CD68 +, NKG2D + and CD11b + cells only in DA rats, with a differential change in IL-10 (decrease in DA, increase in AO) emphasizes the inflammatory character of MLC rat microenvironment of this strain. The absence of similar changes in the spleen (at the same tissue load of cadmium as MLC) indicates the influence of damaged intestinal tissue on the activity of regional lymph nodes, and the more intense response of MLC DA soy reflects greater efforts to prevent systemic immune response to changes in intestinal homeostasis.",
publisher = "Belgrade: Immunological Society of Serbia",
journal = "VII Naučni sastanak Društva imunologa Srbije, Belgrade, Serbia, 27-28 april 2016, Knjiga apstrakata",
title = "Differential strain impact on immune reactivity: insights from regional immune responses in rats, Diferencijalni uticaj soja na imunsku reaktivnost: uvid iz regionalnih imunskih odgovora kod pacova",
pages = "10",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4854"
}

Ninkov, M., Popov Aleksandrov, A., Mirkov, I., Demenesku, J., Brceski, I., Tolinacki, M., Jovanovic, S., Mileusnić, D., Kataranovski, D.,& Kataranovski, M.. (2016). Differential strain impact on immune reactivity: insights from regional immune responses in rats. in VII Naučni sastanak Društva imunologa Srbije, Belgrade, Serbia, 27-28 april 2016, Knjiga apstrakata
Belgrade: Immunological Society of Serbia., 10.
https://hdl.handle.net/21.15107/rcub_ibiss_4854

Ninkov M, Popov Aleksandrov A, Mirkov I, Demenesku J, Brceski I, Tolinacki M, Jovanovic S, Mileusnić D, Kataranovski D, Kataranovski M. Differential strain impact on immune reactivity: insights from regional immune responses in rats. in VII Naučni sastanak Društva imunologa Srbije, Belgrade, Serbia, 27-28 april 2016, Knjiga apstrakata. 2016;:10.
https://hdl.handle.net/21.15107/rcub_ibiss_4854 .

Ninkov, Marina, Popov Aleksandrov, Aleksandra, Mirkov, Ivana, Demenesku, Jelena, Brceski, Ilija, Tolinacki, Maja, Jovanovic, Sofija, Mileusnić, Dina, Kataranovski, Dragan, Kataranovski, Milena, "Differential strain impact on immune reactivity: insights from regional immune responses in rats" in VII Naučni sastanak Društva imunologa Srbije, Belgrade, Serbia, 27-28 april 2016, Knjiga apstrakata (2016):10,
https://hdl.handle.net/21.15107/rcub_ibiss_4854 .

TY  - CONF
AU  - Mirkov, Ivana
AU  - Popov Aleksandrov, Aleksandra
AU  - Demenesku, Jelena
AU  - Ninkov, Marina
AU  - Mileusnić, Dina
AU  - Zolotarevski, Lidija
AU  - Subota, Vesna
AU  - Kataranovski, Dragan
AU  - Kataranovski, Milena
PY  - 2016
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4853
AB  - Warfarin is an anticoagulant that is widely used in the prevention and treatment of thromboembolic disorders in humans. Numerous side effects of oral therapy with this agent are known, which has led to the recommendation for transdermal administration of this agent. This study examined the effect of oral warfarin consumption (0.35 mg / l and 3.5 mg / l in drinking water, 30 days) on the intestinal immune system in rats, as well as the systemic effect (on peripheral blood leukocytes) of epicutaneous administration of this agent. µg or 100 µg, once a day, for three days).The anticoagulant effect, determined on the basis of the increase in prothrombin time, was observed after oral consumption of both doses, as well as after epicutaneous application. Orally administered warfarin leads to histologically evident damage to intestinal tissue and inflammation (cellular infiltration, myeloperoxidase activity, malodialdehyde content and superoxide dismutase and catalase activities), as well as increased concentrations of proinflammatory cytokines (IFN-γ, IL-17) in intestinal homogenate.In mesenteric lymph nodes, however, suppression of the immune response has been observed (decreased ability of cells to proliferate and produce IFN-γ and IL-17 in response to cannavalin A stimulation). Decreased production of IL-10 by mesenteric lymph node cells indicates the formation of a microenvironment that does not allow the activation of a potentially harmful immune response in this tissue. Epicutaneous administration of a higher dose of warfarin leads to an increase in the number of neutrophilic leukocytes and intracellular myeloperoxidase activity, as well as an increase in granular CD11b + cells. In contrast to this increase, a decrease in TNF and IL-6 production as well as mRNA levels for these cytokines was observed.After administration of a higher dose of warfarin, there is a decrease in the number of mononuclear cells with an increase in the presence of CD11b + in this population, but without an effect on cytokine production, indicating the differential effects of transdermal administration of warfarin. Taken together, the results indicate the need to monitor the (adverse) effects of warfarin therapy.
PB  - Belgrade: Immunological Society of Serbia
C3  - VII Naučni sastanak Društva imunologa Srbije, Belgrade, Serbia, 27-28 april 2016, Knjiga apstrakata
T1  - Immunomodulating effect of oral and transdermal varfarine therapy
T1  - Imunomodulatorni efekti oralne i transdermalne terapije varfarinom
SP  - 33
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4853
ER  - 

@conference{
author = "Mirkov, Ivana and Popov Aleksandrov, Aleksandra and Demenesku, Jelena and Ninkov, Marina and Mileusnić, Dina and Zolotarevski, Lidija and Subota, Vesna and Kataranovski, Dragan and Kataranovski, Milena",
year = "2016",
abstract = "Warfarin is an anticoagulant that is widely used in the prevention and treatment of thromboembolic disorders in humans. Numerous side effects of oral therapy with this agent are known, which has led to the recommendation for transdermal administration of this agent. This study examined the effect of oral warfarin consumption (0.35 mg / l and 3.5 mg / l in drinking water, 30 days) on the intestinal immune system in rats, as well as the systemic effect (on peripheral blood leukocytes) of epicutaneous administration of this agent. µg or 100 µg, once a day, for three days).The anticoagulant effect, determined on the basis of the increase in prothrombin time, was observed after oral consumption of both doses, as well as after epicutaneous application. Orally administered warfarin leads to histologically evident damage to intestinal tissue and inflammation (cellular infiltration, myeloperoxidase activity, malodialdehyde content and superoxide dismutase and catalase activities), as well as increased concentrations of proinflammatory cytokines (IFN-γ, IL-17) in intestinal homogenate.In mesenteric lymph nodes, however, suppression of the immune response has been observed (decreased ability of cells to proliferate and produce IFN-γ and IL-17 in response to cannavalin A stimulation). Decreased production of IL-10 by mesenteric lymph node cells indicates the formation of a microenvironment that does not allow the activation of a potentially harmful immune response in this tissue. Epicutaneous administration of a higher dose of warfarin leads to an increase in the number of neutrophilic leukocytes and intracellular myeloperoxidase activity, as well as an increase in granular CD11b + cells. In contrast to this increase, a decrease in TNF and IL-6 production as well as mRNA levels for these cytokines was observed.After administration of a higher dose of warfarin, there is a decrease in the number of mononuclear cells with an increase in the presence of CD11b + in this population, but without an effect on cytokine production, indicating the differential effects of transdermal administration of warfarin. Taken together, the results indicate the need to monitor the (adverse) effects of warfarin therapy.",
publisher = "Belgrade: Immunological Society of Serbia",
journal = "VII Naučni sastanak Društva imunologa Srbije, Belgrade, Serbia, 27-28 april 2016, Knjiga apstrakata",
title = "Immunomodulating effect of oral and transdermal varfarine therapy, Imunomodulatorni efekti oralne i transdermalne terapije varfarinom",
pages = "33",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4853"
}

Mirkov, I., Popov Aleksandrov, A., Demenesku, J., Ninkov, M., Mileusnić, D., Zolotarevski, L., Subota, V., Kataranovski, D.,& Kataranovski, M.. (2016). Immunomodulating effect of oral and transdermal varfarine therapy. in VII Naučni sastanak Društva imunologa Srbije, Belgrade, Serbia, 27-28 april 2016, Knjiga apstrakata
Belgrade: Immunological Society of Serbia., 33.
https://hdl.handle.net/21.15107/rcub_ibiss_4853

Mirkov I, Popov Aleksandrov A, Demenesku J, Ninkov M, Mileusnić D, Zolotarevski L, Subota V, Kataranovski D, Kataranovski M. Immunomodulating effect of oral and transdermal varfarine therapy. in VII Naučni sastanak Društva imunologa Srbije, Belgrade, Serbia, 27-28 april 2016, Knjiga apstrakata. 2016;:33.
https://hdl.handle.net/21.15107/rcub_ibiss_4853 .

Mirkov, Ivana, Popov Aleksandrov, Aleksandra, Demenesku, Jelena, Ninkov, Marina, Mileusnić, Dina, Zolotarevski, Lidija, Subota, Vesna, Kataranovski, Dragan, Kataranovski, Milena, "Immunomodulating effect of oral and transdermal varfarine therapy" in VII Naučni sastanak Društva imunologa Srbije, Belgrade, Serbia, 27-28 april 2016, Knjiga apstrakata (2016):33,
https://hdl.handle.net/21.15107/rcub_ibiss_4853 .

TY  - JOUR
AU  - Zolotarevski, Lidija
AU  - Jović, Milena
AU  - Popov Aleksandrov, Aleksandra
AU  - Milosavljević, Petar
AU  - Brajušković, Goran
AU  - Demenesku, Jelena
AU  - Mirkov, Ivana
AU  - Ninkov, Marina
AU  - Kataranovski, Dragan
AU  - Kataranovski, Milena
PY  - 2016
UR  - http://www.tandfonline.com/doi/full/10.3109/15569527.2015.1008701
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2971
AB  - CONTEXT: Skin is the target of both acute and chronic exposure to warfarin, coumarin anticoagulant. Single exposure of rat skin to this agent induces early (24 h following epicutaneous administration) local response which might be part of inflammatory/reparatory homeostatic program or introduction to pathological events in exposed skin. OBJECTIVE: To examine time-dependent changes in skin of rats exposed to epicutaneously applied warfarin. MATERIALS AND METHODS: The effect of low (10 μg) and high (100 μg) doses of warfarin on histologically evident changes of epidermis (epidermal thickness) and dermis (numbers of mesenchymal cells and dermal capillaries), skin cell proliferative activity (Ki67(+) and PCNA(+) cells) and apoptotic (TUNEL(+)) and necrotic (ultra structural appearance) cells was examined one, three and seven days after the application. RESULTS: Both warfarin doses affected the majority of skin cell activity, but with differential time-course of skin epidermal and dermal cells state/activity. The occurrence of necrotic/apoptotic epidermal and dermal cells was noted the first day after the application and the activities which point to tissue reparation/remodeling were observed seven days after skin exposure to this agent. DISCUSSION: The observed pattern of changes (early evidence of cell/tissue injury which was later followed by signs of cell activity characteristic for tissue reparation/remodeling) implied warfarin-induced toxicity in skin cells as stimulus for subsequent activities relevant for tissue homeostasis. CONCLUSION: The data presented provide new and additional information concerning skin responses to warfarin that gains access to this tissue.
T2  - Cutaneous and Ocular Toxicology
T2  - Cutaneous and Ocular Toxicology
T1  - Skin response to epicutaneous application of anticoagulant rodenticide warfarin is characterized by differential time- and dose-dependent changes in cell activity.
IS  - 1
VL  - 35
DO  - 10.3109/15569527.2015.1008701
SP  - 41
EP  - 48
ER  - 

@article{
author = "Zolotarevski, Lidija and Jović, Milena and Popov Aleksandrov, Aleksandra and Milosavljević, Petar and Brajušković, Goran and Demenesku, Jelena and Mirkov, Ivana and Ninkov, Marina and Kataranovski, Dragan and Kataranovski, Milena",
year = "2016",
abstract = "CONTEXT: Skin is the target of both acute and chronic exposure to warfarin, coumarin anticoagulant. Single exposure of rat skin to this agent induces early (24 h following epicutaneous administration) local response which might be part of inflammatory/reparatory homeostatic program or introduction to pathological events in exposed skin. OBJECTIVE: To examine time-dependent changes in skin of rats exposed to epicutaneously applied warfarin. MATERIALS AND METHODS: The effect of low (10 μg) and high (100 μg) doses of warfarin on histologically evident changes of epidermis (epidermal thickness) and dermis (numbers of mesenchymal cells and dermal capillaries), skin cell proliferative activity (Ki67(+) and PCNA(+) cells) and apoptotic (TUNEL(+)) and necrotic (ultra structural appearance) cells was examined one, three and seven days after the application. RESULTS: Both warfarin doses affected the majority of skin cell activity, but with differential time-course of skin epidermal and dermal cells state/activity. The occurrence of necrotic/apoptotic epidermal and dermal cells was noted the first day after the application and the activities which point to tissue reparation/remodeling were observed seven days after skin exposure to this agent. DISCUSSION: The observed pattern of changes (early evidence of cell/tissue injury which was later followed by signs of cell activity characteristic for tissue reparation/remodeling) implied warfarin-induced toxicity in skin cells as stimulus for subsequent activities relevant for tissue homeostasis. CONCLUSION: The data presented provide new and additional information concerning skin responses to warfarin that gains access to this tissue.",
journal = "Cutaneous and Ocular Toxicology, Cutaneous and Ocular Toxicology",
title = "Skin response to epicutaneous application of anticoagulant rodenticide warfarin is characterized by differential time- and dose-dependent changes in cell activity.",
number = "1",
volume = "35",
doi = "10.3109/15569527.2015.1008701",
pages = "41-48"
}

Zolotarevski, L., Jović, M., Popov Aleksandrov, A., Milosavljević, P., Brajušković, G., Demenesku, J., Mirkov, I., Ninkov, M., Kataranovski, D.,& Kataranovski, M.. (2016). Skin response to epicutaneous application of anticoagulant rodenticide warfarin is characterized by differential time- and dose-dependent changes in cell activity.. in Cutaneous and Ocular Toxicology, 35(1), 41-48.
https://doi.org/10.3109/15569527.2015.1008701

Zolotarevski L, Jović M, Popov Aleksandrov A, Milosavljević P, Brajušković G, Demenesku J, Mirkov I, Ninkov M, Kataranovski D, Kataranovski M. Skin response to epicutaneous application of anticoagulant rodenticide warfarin is characterized by differential time- and dose-dependent changes in cell activity.. in Cutaneous and Ocular Toxicology. 2016;35(1):41-48.
doi:10.3109/15569527.2015.1008701 .

Zolotarevski, Lidija, Jović, Milena, Popov Aleksandrov, Aleksandra, Milosavljević, Petar, Brajušković, Goran, Demenesku, Jelena, Mirkov, Ivana, Ninkov, Marina, Kataranovski, Dragan, Kataranovski, Milena, "Skin response to epicutaneous application of anticoagulant rodenticide warfarin is characterized by differential time- and dose-dependent changes in cell activity." in Cutaneous and Ocular Toxicology, 35, no. 1 (2016):41-48,
https://doi.org/10.3109/15569527.2015.1008701 . .

TY  - JOUR
AU  - Demenesku, Jelena
AU  - Popov Aleksandrov, Aleksandra
AU  - Mirkov, Ivana
AU  - Ninkov, Marina
AU  - Zolotarevski, Lidija
AU  - Kataranovski, Dragan
AU  - Brceski, Ilija
AU  - Kataranovski, Milena
PY  - 2016
UR  - http://linkinghub.elsevier.com/retrieve/pii/S037842741630128X
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2532
AB  - The impact of genetic background on effects of acute i.p. cadmium administration (0.5 mg/kg and 1 mg/kg) on basic immune activity of spleen and lungs was examined in two rat strains, Albino Oxford (AO) and Dark Agouti (DA), known to react differently to chemicals. More pronounced inhibition of Concanavalin A (ConA)-induced and Interleukin (IL)-2 stimulated spleen cell proliferation as well as higher levels of nitric oxide (known to decrease cell's proliferative ability) in DA rats at 1 mg/kg, along with greater inhibition of ConA-induced Interferon (IFN-γ)-production by total and mononuclear (MNC) spleen cells and IL-17 production by spleen MNC in DA vs. AO rats at this dose show greater susceptibility of this strain to Cd effects on spleen cells response. More pronounced infiltration of neutrophils/CD11b+ cells to lungs of DA rats treated with 1 mg/kg of Cd and decreased IL-17 lung cell responses noted solely in DA rats speaks in favor of their higher susceptibility to this metal. However, lack of strain disparity in lung cells IFN-γ responses show that there are regional differences as well. Novel data from this study depict complexity of the influence of genetic background on the effects of cadmium on host immune reactivity.
T2  - Toxicology Letters
T1  - Strain differences of cadmium-induced toxicity in rats: Insight from spleen and lung immune responses
VL  - 256
DO  - 10.1016/j.toxlet.2016.05.022
SP  - 33
EP  - 43
ER  - 

@article{
author = "Demenesku, Jelena and Popov Aleksandrov, Aleksandra and Mirkov, Ivana and Ninkov, Marina and Zolotarevski, Lidija and Kataranovski, Dragan and Brceski, Ilija and Kataranovski, Milena",
year = "2016",
abstract = "The impact of genetic background on effects of acute i.p. cadmium administration (0.5 mg/kg and 1 mg/kg) on basic immune activity of spleen and lungs was examined in two rat strains, Albino Oxford (AO) and Dark Agouti (DA), known to react differently to chemicals. More pronounced inhibition of Concanavalin A (ConA)-induced and Interleukin (IL)-2 stimulated spleen cell proliferation as well as higher levels of nitric oxide (known to decrease cell's proliferative ability) in DA rats at 1 mg/kg, along with greater inhibition of ConA-induced Interferon (IFN-γ)-production by total and mononuclear (MNC) spleen cells and IL-17 production by spleen MNC in DA vs. AO rats at this dose show greater susceptibility of this strain to Cd effects on spleen cells response. More pronounced infiltration of neutrophils/CD11b+ cells to lungs of DA rats treated with 1 mg/kg of Cd and decreased IL-17 lung cell responses noted solely in DA rats speaks in favor of their higher susceptibility to this metal. However, lack of strain disparity in lung cells IFN-γ responses show that there are regional differences as well. Novel data from this study depict complexity of the influence of genetic background on the effects of cadmium on host immune reactivity.",
journal = "Toxicology Letters",
title = "Strain differences of cadmium-induced toxicity in rats: Insight from spleen and lung immune responses",
volume = "256",
doi = "10.1016/j.toxlet.2016.05.022",
pages = "33-43"
}

Demenesku, J., Popov Aleksandrov, A., Mirkov, I., Ninkov, M., Zolotarevski, L., Kataranovski, D., Brceski, I.,& Kataranovski, M.. (2016). Strain differences of cadmium-induced toxicity in rats: Insight from spleen and lung immune responses. in Toxicology Letters, 256, 33-43.
https://doi.org/10.1016/j.toxlet.2016.05.022

Demenesku J, Popov Aleksandrov A, Mirkov I, Ninkov M, Zolotarevski L, Kataranovski D, Brceski I, Kataranovski M. Strain differences of cadmium-induced toxicity in rats: Insight from spleen and lung immune responses. in Toxicology Letters. 2016;256:33-43.
doi:10.1016/j.toxlet.2016.05.022 .

Demenesku, Jelena, Popov Aleksandrov, Aleksandra, Mirkov, Ivana, Ninkov, Marina, Zolotarevski, Lidija, Kataranovski, Dragan, Brceski, Ilija, Kataranovski, Milena, "Strain differences of cadmium-induced toxicity in rats: Insight from spleen and lung immune responses" in Toxicology Letters, 256 (2016):33-43,
https://doi.org/10.1016/j.toxlet.2016.05.022 . .

TY  - JOUR
AU  - Ninkov, Marina
AU  - Popov Aleksandrov, Aleksandra
AU  - Mirkov, Ivana
AU  - Demenesku, Jelena
AU  - Tucović, Dina
AU  - Jovanović Stojanov, Sofija
AU  - Golic, Natasa
AU  - Tolinacki, Maja
AU  - Kataranovski, Dragan
AU  - Brceski, Ilija
AU  - Kataranovski, Milena
PY  - 2016
UR  - https://www.sciencedirect.com/science/article/pii/S0278691516302423?via%3Dihub
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3378
AB  - Influence of genetic background on toxicity of oral cadmium (Cd) administration (30 days, in drinking
water; 5 ppm and 50 ppm of cadmium) was examined in Albino Oxford (AO) and Dark Agouti (DA) rats.
Similar cadmium deposition was noted in gut and draining mesenteric lymph nodes (MLN) of both
strains but intensity and/or the pattern of responses to cadmium in these tissues differ. Less intense
intestinal damage and leukocyte infiltration was observed in gut of cadmium-exposed AO rats. While
gut-associated lymph node cells of DA rats responded to cadmium with an increase of cell proliferation,
oxidative activity, IFN-g, IL-17 production and expression, no changes of these activities of MLN cells of
cadmium-treated AO rats were observed. Spleen, which accumulated cadmium comparable to MLN,
responded to metal by drop in cell viability and by reduced responsiveness of proliferation and cytokine
production to stimulation in DA rats solely, which suggest tissue dependence of cadmium effects. More
pronounced cadmium effects on MLN and spleen cells of DA rats (which accumulated similar cadmium
doses as AO rats), showed greater susceptibility of this strain to cadmium. The results presented, for the
first time, depict the influence of genetic background to effects of oral cadmium administration.
T2  - Food and Chemical Toxicology
T1  - Strain differences in toxicity of oral cadmium intake in rats
VL  - 96
DO  - 10.1016/j.fct.2016.07.021
SP  - 11
EP  - 23
ER  - 

@article{
author = "Ninkov, Marina and Popov Aleksandrov, Aleksandra and Mirkov, Ivana and Demenesku, Jelena and Tucović, Dina and Jovanović Stojanov, Sofija and Golic, Natasa and Tolinacki, Maja and Kataranovski, Dragan and Brceski, Ilija and Kataranovski, Milena",
year = "2016",
abstract = "Influence of genetic background on toxicity of oral cadmium (Cd) administration (30 days, in drinking
water; 5 ppm and 50 ppm of cadmium) was examined in Albino Oxford (AO) and Dark Agouti (DA) rats.
Similar cadmium deposition was noted in gut and draining mesenteric lymph nodes (MLN) of both
strains but intensity and/or the pattern of responses to cadmium in these tissues differ. Less intense
intestinal damage and leukocyte infiltration was observed in gut of cadmium-exposed AO rats. While
gut-associated lymph node cells of DA rats responded to cadmium with an increase of cell proliferation,
oxidative activity, IFN-g, IL-17 production and expression, no changes of these activities of MLN cells of
cadmium-treated AO rats were observed. Spleen, which accumulated cadmium comparable to MLN,
responded to metal by drop in cell viability and by reduced responsiveness of proliferation and cytokine
production to stimulation in DA rats solely, which suggest tissue dependence of cadmium effects. More
pronounced cadmium effects on MLN and spleen cells of DA rats (which accumulated similar cadmium
doses as AO rats), showed greater susceptibility of this strain to cadmium. The results presented, for the
first time, depict the influence of genetic background to effects of oral cadmium administration.",
journal = "Food and Chemical Toxicology",
title = "Strain differences in toxicity of oral cadmium intake in rats",
volume = "96",
doi = "10.1016/j.fct.2016.07.021",
pages = "11-23"
}

Ninkov, M., Popov Aleksandrov, A., Mirkov, I., Demenesku, J., Tucović, D., Jovanović Stojanov, S., Golic, N., Tolinacki, M., Kataranovski, D., Brceski, I.,& Kataranovski, M.. (2016). Strain differences in toxicity of oral cadmium intake in rats. in Food and Chemical Toxicology, 96, 11-23.
https://doi.org/10.1016/j.fct.2016.07.021

Ninkov M, Popov Aleksandrov A, Mirkov I, Demenesku J, Tucović D, Jovanović Stojanov S, Golic N, Tolinacki M, Kataranovski D, Brceski I, Kataranovski M. Strain differences in toxicity of oral cadmium intake in rats. in Food and Chemical Toxicology. 2016;96:11-23.
doi:10.1016/j.fct.2016.07.021 .

Ninkov, Marina, Popov Aleksandrov, Aleksandra, Mirkov, Ivana, Demenesku, Jelena, Tucović, Dina, Jovanović Stojanov, Sofija, Golic, Natasa, Tolinacki, Maja, Kataranovski, Dragan, Brceski, Ilija, Kataranovski, Milena, "Strain differences in toxicity of oral cadmium intake in rats" in Food and Chemical Toxicology, 96 (2016):11-23,
https://doi.org/10.1016/j.fct.2016.07.021 . .

TY  - THES
AU  - Ninkov, Marina
PY  - 2016
UR  - http://uvidok.rcub.bg.ac.rs/handle/123456789/1680
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2517
AB  - Kadmijum (Cd) je teški metal koji se nalazi u svim delovima životne sredine,
nema poznatu biološku funkciju i ima štetno dejstvo na žive sisteme. Najčešći put
izloženosti Cd je oralni, preko kontaminirane vode i hrane, kada je primarna meta
toksičnosti ovog metala gastrointestinalni trakt. Poznato je da Cd oštećuje tkivo creva i
remeti funkciju epitelne barijere koja je neophodna za održavanje imunske homeostaze,
međutim mehanizmi imunotoksičnosti u ovoj regiji nisu dovoljno ispitani. Dodatno,
poznato je da toksični efekti Cd mogu da zavise i od genetske osnove / soja
eksperimentalnih životinja, ali sojne razlike u intestinalnoj toksičnosti oralnog unosa Cd
do sada nisu ispitane.
Ova disertacija je imala za cilj karakterizaciju efekta subhronične oralne primene
Cd na imunski sistem creva pacova. Pacovi su bili 30 dana oralno (u vodi za piće)
izloženi Cd u obliku kadmijum hlorida (CdCl2) u koncentraciji 5 ppm (5 mg Cd/l) i 50
ppm (50 mg Cd/l) Cd, što odgovara dozama prisutnim u životnoj sredini. U okviru
lokalnog imunomodulatornog efekta Cd ispitivani su osnovni parametri imunskog
odgovora u duodenumu (kao mestu najveće apsorpcije Cd) i mezenteričnim limfnim
čvorovima (MLČ) koji dreniraju intestinum. U duodenumu su ispitani pokazatelji
tkivnog oštećenja, oksidativnog stresa i zapaljenskih promena, a u MLČ su ispitane
osnovne fenotpiske karakteristike i parametri aktivnosti ćelija ovog limfnog tkiva
(celularnost, proliferacija, citokinski odgovor, urođeno-imunska aktivnost ćelija). Pored
lokalnog, ispitan je i sistemski odgovor na oralni unos Cd uključujući humoralne i
ćelijske parametre zapaljenske reakcije u krvi (promene hematoloških parametara,
prisustvo medijatora inflamacije i oksidativnog stresa), kao i oksidativni stres i osnovne
karakteristike urođenog i adaptivnog imunskog odgovora u slezini, limfnom organu u
kome se uspostavlja imunski odgovor na antigene iz krvi. U cilju ispitivanja uticaja
genetske osnove na intestinalnu i sistemsku imunotoksičnost oralne izloženosti Cd,
lokalni i sistemski efekti su analizirani kod dva soja pacova, Dark Agouti (DA) i Albino
Oxford (AO), koji uspostavljaju kvalitativno i / ili kvantitativno različit imunski
odgovor na iste stimuluse.
Studija je pokazala da oralni tretman Cd dovodi do dozno zavisne akumulacije
metala u crevu, MLČ i slezini, slično kod DA i AO pacova, što pokazuje da genetska
osnova ne utiče na nivoe deponovanog metala. I pored sličnih koncentracija Cd u crevu
oba soja, izraženiji infiltrat mononuklearnih leukocita u tkivu creva, veći stepen nekroze
enterocita [meren povećanjem markera nekroze HMGB1 (engl., High Mobility Group
Box 1) molekula] i povećana produkcija proinflamatornih citokina (faktora nekroze
tumora/TNF, interferona-gama/IFN-γ, interleukina-17/IL-17) pokazani su u tkivu creva
DA pacova u odnosu na pacove AO soja. Promena aktivnosti osnovnih enzima
antioksidativne odbrane (superoksid dismutaze/SOD i katalaze/CAT), u crevu DA
pacova i SOD kod AO pacova, koja predstavlja pokušaj domaćina da ukloni reaktivne
kiseonične vrste (engl., Reactive Oxygen Species/ROS) i ograniči oštećenje tkiva, kao i
glutation-s-transferaze/GST (enzima odgovornog za vezivanje elektrofilnih supstanci
kao što je Cd za redukovani glutation, GSH) bila je takođe izraženija kod pacova DA
soja. Ovakav tip promena je verovatno u osnovi povećanja nivoa lipidnih peroksida
(mereno promenama malondialdehida/MDA) kod AO pacova. Oralni tretman Cd
dovodi do smanjene zastupljenosti laktobacila u crevu DA pacova što može doprineti
razvoju proinflamatornog citokinskog odgovora na Cd, dok relativno očuvanje
komensalne flore kod AO pacova (uz značajan porast zastupljenosti L. johnsonii i L.
murinus) može biti od značaja za očuvanje integriteta crevne barijere i izostanak
lokalnog inflamatornog citokinskog odgovora kod ovog soja pacova.
Oralni tretman Cd je uticao na aktivnost MLČ kod oba soja pacova (porast mase i
celularnosti MLČ, produkcija ROS). Ipak, Cd je indukovao ekspresiju gena za
metalotioneine/MT kao i proinflamatorni imunski odgovor (proliferativna aktivnost
ćelija MLČ, oksidativne aktivnosti, Th1/Tip1 i Th17/tip17 odgovor) i inhibirao antiinflamatorni
odgovor (ekspresija gena i produkcija interleukina-10/IL-10) samo u MLČ
DA pacova. Veći stepen oštećenja i nekroze epitela creva koji je zapažen kod tretiranih
DA (u odnosu na AO pacove) je najverovatniji faktor koji je doveo do stimulacije
proinflamatornog odgovora u MLČ kod DA pacova. Promene u MLČ DA pacova
ukazuju da Cd remeti tolerogenu imunsku sredinu u crevu indukcijom kako urođenog
tako i stečenog imunskog odgovora.
Iako je ispitivanjem sistemskog efekta oralno unetog Cd ukazano, generalno, na
slab uticaj metala na osnovne hematološke i biohemijske parametare u perifernoj krvi,
zapažen je efekat na antioksidativne aktivnosti eritrocita kod oba soja pacova. Povećani
nivoi HMGB1 molekula u krvi samo DA pacova sugerišu veći stepen oštećenja organa i
inflamatorni karakter imunskog odgovora na Cd kod ovog soja pacova.
Iako se ista količina Cd deponuje u MLČ i slezini, odgovor u ova dva imunska
organa se razlikuje čime je pokazano da je za praćenje efekata Cd od velike važnosti i
mikrosredina ispitivanog tkiva. Za razliku od MLČ, u slezini oralni tretman Cd nije
uticao na masu i celularnost ali je doveo do smanjene vijabilnosti i smanjene
proliferativne aktivnosti ćelija slezine, dok je slično kao i u MLČ, zabeležena povećana
oksidativna aktivnost ćelija slezine (aktivnost mijeloperoksidaze/MPO, produkcija azotoksida/
NO) i povećana nestimulisana produkcija proinflamatornih citokina
(interleukina-1 beta/IL-1ß, IFN-γ, IL-17) i to samo kod DA pacova. Ovaj
proinflamatorni citokinski odgovor ćelija slezine kod DA pacova može se dovesti u
vezu sa povećanim nivoom HMGB1 molekula u slezini. Izraženiji proinflamatorni
odgovor na oralni tretman Cd u crevu kao i u MLČ i slezini DA u odnosu na AO pacove
(kod kojih su nađene slične koncentracije deponovanog Cd) pokazuju da su DA pacovi
podložniji oralnom subhroničnom tretmanu ovim metalom.
Rezultati ove studije doprinose razumevanju mehanizama koji leže u osnovi
toksičnih efekata Cd na imunski odgovor u crevu, pokazujući po prvi put uticaj ovog
metala na homeostazu urođenih i adaptivnih komponenti imunskog odgovora u MLČ.
Ona je istovremeno pokazala i značaj tkiva u ispoljavanju imunotoksičnosti Cd. Takođe,
ova studija je po prvi put ukazala na uticaj genetske osnove na efekte oralno unešenog
Cd, sugerišući na značaj pažljivog odabira soja eksperimentalnih životinja koji će se
koristiti za analizu imunotoksičnih efekata ovog metala.
AB  - Cadmium (Cd) is a heavy metal which is found in every part of the environment,
it does not have any known biological function and has an adverse effect upon the living
systems. The most common way of Cd exposure is orally, through contaminated water
and food, where the prime target of this metal toxicity is the gastrointestinal tract. It is
known that Cd causes damage to intestinal tissue and disrupts the epithelial barrier
function which is necessary for maintaining immune homeostasis, however, the
immunotoxicity mechanisms in this region have not been examined sufficiently.
Additionally, it is known that Cd toxic effects may depend also on genetic background /
strain of experimental animals, but the strain-dependent differences in intestinal toxicity
of oral Cd intake have not been examined to date.
This dissertation was aimed at characterization of the effect of subchronic oral
Cd administration on rat’s intestinal immune system. Rats were, for 30 days, orally (in
drinking water) exposed to Cd in the form of cadmium chloride (CdCl2) at
concentration of 5 ppm (5 mg Cd/l) and 50 ppm and (50 mg Cd/l) of Cd, which
corresponds to the doses present in the environment. Within the local
immunomodulatory Cd effect, basic parameters of immune response in duodenum
(region of greatest Cd absorption) and in mesenteric lymph nodes (MLN) which drain
intestine, were investigated. The indicators of tissue damage, oxidative stress and
inflammatory changes were tested in duodenum, whereas in the MLN basic phenotype
characteristics and parameters of this lymph tissue cells' activities (cellularity,
proliferation, cytokine responses, and innate-immune cell activity) were tested. Besides
the local, the systemic response to oral Cd intake was tested as well, including humoral
and cellular parameters of the inflammatory reaction in blood (changes in hematological
parameters, presence of inflammatory mediators and oxidative stress), as well as
oxidative stress and basic characteristics of the innate and adaptive immune response in
the spleen, a lymph organ in which immune response to blood borne antigens are
generated. Aiming to test the contribution of genetic background to intestinal and
systemic immunotoxicity of oral Cd exposure, local and systemic effects were analyzed
in two rat strains, Dark Agouti (DA) and Albino Oxford (AO), which establish
qualitatively and/or quantitative different immune response to the same stimuli.
The study has shown that oral Cd treatment leads to dose-dependent
accumulation of this metal in intestine, MLN and spleen, similarly in DA and AO rats,
which demonstrates that genetic background has no effect on the metal deposition
levels. Despite similar Cd concentrations in the intestine of both rat strains, more
pronounced mononuclear leukocytes infiltrates in intestinal tissue, higher degree of
enterocytes necrosis [measured by increased necrosis marker HMGB1 (High mobility
group box 1) molecule] and the increased production of proinflammatory cytokines
(tumor necrosis factor/TNF, interferone-gamma/IFN-γ, interleukin-17/IL-17) were
shown in intestinal tissue of DA rats compared to rats of AO strain. The change in
activity of basic enzymes of anti-oxidative defense (superoxide dismutase/SOD and
catalase/CAT), in intestine of DA rats and SOD in AO rats, which depicts host tissue
attempt to counterattack reactive oxygen species (ROS) and limit tissue damage, as well
as glutathione-s-transferase/GST (the enzyme responsible for electrophilic substances
binding, such as Cd, to the reduced form of glutathione, GSH), was also more expressed
in rats of DA strain. Such type of changes is probably in the background of the
increased level of lipid peroxides (measured by the changes of malondialdehyde/MDA)
in AO rats. Oral Cd treatment results in reduced prevalence of lactobacilli in DA rats'
intestine which may contribute to the development of proinflammatory cytokine
response to Cd, whereas relative preservation of commensal flora in AO rats (along
with significant increase in prevalence of L. johnsonii and L. Murinus) might be of
significance for preservation of gut barrier integrity and absence of the local
inflammatory cytokine response in this strain of rats.
Oral Cd treatment affected the MLN activity in both strains of rats (increase of
MLN mass and cellularity, ROS production). Nevertheless, Cd induced
metalotioneinas/MT gene expression as well as proinflammatory immune response
(MLN cells' proliferative activity, oxidative activities, Th1/Type1 and Th17/Type17
response) and inhibited anti-inflammatory response (interleukine-10/IL-10 gene
expression and production) only in MLN of DA rats. Higher degree of intestinal
epithelium damage and necrosis observed in DA treated rats (compared to AO rats) is
the most likely factor which stimulated proinflammatory response in MLN of DA rats.
The changes in MLN of DA rats indicate that Cd disrupts the tolerogenic immune
environment in the gut by induction of both innate and the acquired immune responses.
Although the investigation of the systemic effect of orally administered Cd
indicated, in general, slight effect of the metal on the basic hematological and
biochemical parameters in the peripheral blood, the effect on anti-oxidative activities of
erythrocytes in both strains of rats was noticed. The increased levels of HMGB1
molecule in blood of DA rats only, suggests higher degree of organs damage and
inflammatory character of immune response to Cd in this strain of rats.
Although the same quantity of Cd is deposited in MLN and spleen, the response
in these two immune organs differs, showing that the micro environment of the
examined tissue is also of great importance in observing Cd effects. Unlike MLN, the
oral Cd administration did not affect spleen mass and cellularity but it resulted in
reduced viability and reduced proliferative activity of spleen cells, whereas, similar as in
MLN, the increased oxidative activity of spleen cells (activity of
myeloperoxidase/MPO, nitrogen-oxide/NO production) was noted and the increase of
non-stimulated production of proinflammatory cytokines (interleukine-1 beta/ IL-1ß,
IFN-γ, IL-17) was noted, only in DA rats. This proinflammatory cytokine response of
spleen cells in DA rats may be associated with increased level of HMBG1 molecule in
the spleen. More pronounced proinflammatory response to oral Cd administration in gut
as well as in MLN and spleen of DA rats in comparison to AO rats (in which similar
concentrations of deposited Cd were found) show that DA rats are more susceptible to
oral subchronic administration of this metal.
The results of this study contribute to the understanding of the mechanisms
which underlie the toxic Cd effects on immune response in intestine, for the first time
showing the effect of this metal on homeostasis of innate and adaptive components of
immune response in MLN. At the same time, this study has also shown the significance
of tissue in expressing Cd toxicity. Also, for the first time, this study has indicated the
effect of genetic background on orally administered Cd effects, suggesting the
significance of careful selection of experimental animals to be used in the analysis of
immunotoxic effects of this metal.
PB  - Belgrade: University of Belgrade, Faculty of Biology
T2  - University of Belgrade, Faculty of Biology
T1  - Intestinalni i sistemski imunski efekti oralnog unosa kadmijuma kod pacova
T1  - Intestinal and systemic immune effects
of oral cadmium intake in rats
SP  - 1
EP  - 139
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_2517
ER  - 

@phdthesis{
author = "Ninkov, Marina",
year = "2016",
abstract = "Kadmijum (Cd) je teški metal koji se nalazi u svim delovima životne sredine,
nema poznatu biološku funkciju i ima štetno dejstvo na žive sisteme. Najčešći put
izloženosti Cd je oralni, preko kontaminirane vode i hrane, kada je primarna meta
toksičnosti ovog metala gastrointestinalni trakt. Poznato je da Cd oštećuje tkivo creva i
remeti funkciju epitelne barijere koja je neophodna za održavanje imunske homeostaze,
međutim mehanizmi imunotoksičnosti u ovoj regiji nisu dovoljno ispitani. Dodatno,
poznato je da toksični efekti Cd mogu da zavise i od genetske osnove / soja
eksperimentalnih životinja, ali sojne razlike u intestinalnoj toksičnosti oralnog unosa Cd
do sada nisu ispitane.
Ova disertacija je imala za cilj karakterizaciju efekta subhronične oralne primene
Cd na imunski sistem creva pacova. Pacovi su bili 30 dana oralno (u vodi za piće)
izloženi Cd u obliku kadmijum hlorida (CdCl2) u koncentraciji 5 ppm (5 mg Cd/l) i 50
ppm (50 mg Cd/l) Cd, što odgovara dozama prisutnim u životnoj sredini. U okviru
lokalnog imunomodulatornog efekta Cd ispitivani su osnovni parametri imunskog
odgovora u duodenumu (kao mestu najveće apsorpcije Cd) i mezenteričnim limfnim
čvorovima (MLČ) koji dreniraju intestinum. U duodenumu su ispitani pokazatelji
tkivnog oštećenja, oksidativnog stresa i zapaljenskih promena, a u MLČ su ispitane
osnovne fenotpiske karakteristike i parametri aktivnosti ćelija ovog limfnog tkiva
(celularnost, proliferacija, citokinski odgovor, urođeno-imunska aktivnost ćelija). Pored
lokalnog, ispitan je i sistemski odgovor na oralni unos Cd uključujući humoralne i
ćelijske parametre zapaljenske reakcije u krvi (promene hematoloških parametara,
prisustvo medijatora inflamacije i oksidativnog stresa), kao i oksidativni stres i osnovne
karakteristike urođenog i adaptivnog imunskog odgovora u slezini, limfnom organu u
kome se uspostavlja imunski odgovor na antigene iz krvi. U cilju ispitivanja uticaja
genetske osnove na intestinalnu i sistemsku imunotoksičnost oralne izloženosti Cd,
lokalni i sistemski efekti su analizirani kod dva soja pacova, Dark Agouti (DA) i Albino
Oxford (AO), koji uspostavljaju kvalitativno i / ili kvantitativno različit imunski
odgovor na iste stimuluse.
Studija je pokazala da oralni tretman Cd dovodi do dozno zavisne akumulacije
metala u crevu, MLČ i slezini, slično kod DA i AO pacova, što pokazuje da genetska
osnova ne utiče na nivoe deponovanog metala. I pored sličnih koncentracija Cd u crevu
oba soja, izraženiji infiltrat mononuklearnih leukocita u tkivu creva, veći stepen nekroze
enterocita [meren povećanjem markera nekroze HMGB1 (engl., High Mobility Group
Box 1) molekula] i povećana produkcija proinflamatornih citokina (faktora nekroze
tumora/TNF, interferona-gama/IFN-γ, interleukina-17/IL-17) pokazani su u tkivu creva
DA pacova u odnosu na pacove AO soja. Promena aktivnosti osnovnih enzima
antioksidativne odbrane (superoksid dismutaze/SOD i katalaze/CAT), u crevu DA
pacova i SOD kod AO pacova, koja predstavlja pokušaj domaćina da ukloni reaktivne
kiseonične vrste (engl., Reactive Oxygen Species/ROS) i ograniči oštećenje tkiva, kao i
glutation-s-transferaze/GST (enzima odgovornog za vezivanje elektrofilnih supstanci
kao što je Cd za redukovani glutation, GSH) bila je takođe izraženija kod pacova DA
soja. Ovakav tip promena je verovatno u osnovi povećanja nivoa lipidnih peroksida
(mereno promenama malondialdehida/MDA) kod AO pacova. Oralni tretman Cd
dovodi do smanjene zastupljenosti laktobacila u crevu DA pacova što može doprineti
razvoju proinflamatornog citokinskog odgovora na Cd, dok relativno očuvanje
komensalne flore kod AO pacova (uz značajan porast zastupljenosti L. johnsonii i L.
murinus) može biti od značaja za očuvanje integriteta crevne barijere i izostanak
lokalnog inflamatornog citokinskog odgovora kod ovog soja pacova.
Oralni tretman Cd je uticao na aktivnost MLČ kod oba soja pacova (porast mase i
celularnosti MLČ, produkcija ROS). Ipak, Cd je indukovao ekspresiju gena za
metalotioneine/MT kao i proinflamatorni imunski odgovor (proliferativna aktivnost
ćelija MLČ, oksidativne aktivnosti, Th1/Tip1 i Th17/tip17 odgovor) i inhibirao antiinflamatorni
odgovor (ekspresija gena i produkcija interleukina-10/IL-10) samo u MLČ
DA pacova. Veći stepen oštećenja i nekroze epitela creva koji je zapažen kod tretiranih
DA (u odnosu na AO pacove) je najverovatniji faktor koji je doveo do stimulacije
proinflamatornog odgovora u MLČ kod DA pacova. Promene u MLČ DA pacova
ukazuju da Cd remeti tolerogenu imunsku sredinu u crevu indukcijom kako urođenog
tako i stečenog imunskog odgovora.
Iako je ispitivanjem sistemskog efekta oralno unetog Cd ukazano, generalno, na
slab uticaj metala na osnovne hematološke i biohemijske parametare u perifernoj krvi,
zapažen je efekat na antioksidativne aktivnosti eritrocita kod oba soja pacova. Povećani
nivoi HMGB1 molekula u krvi samo DA pacova sugerišu veći stepen oštećenja organa i
inflamatorni karakter imunskog odgovora na Cd kod ovog soja pacova.
Iako se ista količina Cd deponuje u MLČ i slezini, odgovor u ova dva imunska
organa se razlikuje čime je pokazano da je za praćenje efekata Cd od velike važnosti i
mikrosredina ispitivanog tkiva. Za razliku od MLČ, u slezini oralni tretman Cd nije
uticao na masu i celularnost ali je doveo do smanjene vijabilnosti i smanjene
proliferativne aktivnosti ćelija slezine, dok je slično kao i u MLČ, zabeležena povećana
oksidativna aktivnost ćelija slezine (aktivnost mijeloperoksidaze/MPO, produkcija azotoksida/
NO) i povećana nestimulisana produkcija proinflamatornih citokina
(interleukina-1 beta/IL-1ß, IFN-γ, IL-17) i to samo kod DA pacova. Ovaj
proinflamatorni citokinski odgovor ćelija slezine kod DA pacova može se dovesti u
vezu sa povećanim nivoom HMGB1 molekula u slezini. Izraženiji proinflamatorni
odgovor na oralni tretman Cd u crevu kao i u MLČ i slezini DA u odnosu na AO pacove
(kod kojih su nađene slične koncentracije deponovanog Cd) pokazuju da su DA pacovi
podložniji oralnom subhroničnom tretmanu ovim metalom.
Rezultati ove studije doprinose razumevanju mehanizama koji leže u osnovi
toksičnih efekata Cd na imunski odgovor u crevu, pokazujući po prvi put uticaj ovog
metala na homeostazu urođenih i adaptivnih komponenti imunskog odgovora u MLČ.
Ona je istovremeno pokazala i značaj tkiva u ispoljavanju imunotoksičnosti Cd. Takođe,
ova studija je po prvi put ukazala na uticaj genetske osnove na efekte oralno unešenog
Cd, sugerišući na značaj pažljivog odabira soja eksperimentalnih životinja koji će se
koristiti za analizu imunotoksičnih efekata ovog metala., Cadmium (Cd) is a heavy metal which is found in every part of the environment,
it does not have any known biological function and has an adverse effect upon the living
systems. The most common way of Cd exposure is orally, through contaminated water
and food, where the prime target of this metal toxicity is the gastrointestinal tract. It is
known that Cd causes damage to intestinal tissue and disrupts the epithelial barrier
function which is necessary for maintaining immune homeostasis, however, the
immunotoxicity mechanisms in this region have not been examined sufficiently.
Additionally, it is known that Cd toxic effects may depend also on genetic background /
strain of experimental animals, but the strain-dependent differences in intestinal toxicity
of oral Cd intake have not been examined to date.
This dissertation was aimed at characterization of the effect of subchronic oral
Cd administration on rat’s intestinal immune system. Rats were, for 30 days, orally (in
drinking water) exposed to Cd in the form of cadmium chloride (CdCl2) at
concentration of 5 ppm (5 mg Cd/l) and 50 ppm and (50 mg Cd/l) of Cd, which
corresponds to the doses present in the environment. Within the local
immunomodulatory Cd effect, basic parameters of immune response in duodenum
(region of greatest Cd absorption) and in mesenteric lymph nodes (MLN) which drain
intestine, were investigated. The indicators of tissue damage, oxidative stress and
inflammatory changes were tested in duodenum, whereas in the MLN basic phenotype
characteristics and parameters of this lymph tissue cells' activities (cellularity,
proliferation, cytokine responses, and innate-immune cell activity) were tested. Besides
the local, the systemic response to oral Cd intake was tested as well, including humoral
and cellular parameters of the inflammatory reaction in blood (changes in hematological
parameters, presence of inflammatory mediators and oxidative stress), as well as
oxidative stress and basic characteristics of the innate and adaptive immune response in
the spleen, a lymph organ in which immune response to blood borne antigens are
generated. Aiming to test the contribution of genetic background to intestinal and
systemic immunotoxicity of oral Cd exposure, local and systemic effects were analyzed
in two rat strains, Dark Agouti (DA) and Albino Oxford (AO), which establish
qualitatively and/or quantitative different immune response to the same stimuli.
The study has shown that oral Cd treatment leads to dose-dependent
accumulation of this metal in intestine, MLN and spleen, similarly in DA and AO rats,
which demonstrates that genetic background has no effect on the metal deposition
levels. Despite similar Cd concentrations in the intestine of both rat strains, more
pronounced mononuclear leukocytes infiltrates in intestinal tissue, higher degree of
enterocytes necrosis [measured by increased necrosis marker HMGB1 (High mobility
group box 1) molecule] and the increased production of proinflammatory cytokines
(tumor necrosis factor/TNF, interferone-gamma/IFN-γ, interleukin-17/IL-17) were
shown in intestinal tissue of DA rats compared to rats of AO strain. The change in
activity of basic enzymes of anti-oxidative defense (superoxide dismutase/SOD and
catalase/CAT), in intestine of DA rats and SOD in AO rats, which depicts host tissue
attempt to counterattack reactive oxygen species (ROS) and limit tissue damage, as well
as glutathione-s-transferase/GST (the enzyme responsible for electrophilic substances
binding, such as Cd, to the reduced form of glutathione, GSH), was also more expressed
in rats of DA strain. Such type of changes is probably in the background of the
increased level of lipid peroxides (measured by the changes of malondialdehyde/MDA)
in AO rats. Oral Cd treatment results in reduced prevalence of lactobacilli in DA rats'
intestine which may contribute to the development of proinflammatory cytokine
response to Cd, whereas relative preservation of commensal flora in AO rats (along
with significant increase in prevalence of L. johnsonii and L. Murinus) might be of
significance for preservation of gut barrier integrity and absence of the local
inflammatory cytokine response in this strain of rats.
Oral Cd treatment affected the MLN activity in both strains of rats (increase of
MLN mass and cellularity, ROS production). Nevertheless, Cd induced
metalotioneinas/MT gene expression as well as proinflammatory immune response
(MLN cells' proliferative activity, oxidative activities, Th1/Type1 and Th17/Type17
response) and inhibited anti-inflammatory response (interleukine-10/IL-10 gene
expression and production) only in MLN of DA rats. Higher degree of intestinal
epithelium damage and necrosis observed in DA treated rats (compared to AO rats) is
the most likely factor which stimulated proinflammatory response in MLN of DA rats.
The changes in MLN of DA rats indicate that Cd disrupts the tolerogenic immune
environment in the gut by induction of both innate and the acquired immune responses.
Although the investigation of the systemic effect of orally administered Cd
indicated, in general, slight effect of the metal on the basic hematological and
biochemical parameters in the peripheral blood, the effect on anti-oxidative activities of
erythrocytes in both strains of rats was noticed. The increased levels of HMGB1
molecule in blood of DA rats only, suggests higher degree of organs damage and
inflammatory character of immune response to Cd in this strain of rats.
Although the same quantity of Cd is deposited in MLN and spleen, the response
in these two immune organs differs, showing that the micro environment of the
examined tissue is also of great importance in observing Cd effects. Unlike MLN, the
oral Cd administration did not affect spleen mass and cellularity but it resulted in
reduced viability and reduced proliferative activity of spleen cells, whereas, similar as in
MLN, the increased oxidative activity of spleen cells (activity of
myeloperoxidase/MPO, nitrogen-oxide/NO production) was noted and the increase of
non-stimulated production of proinflammatory cytokines (interleukine-1 beta/ IL-1ß,
IFN-γ, IL-17) was noted, only in DA rats. This proinflammatory cytokine response of
spleen cells in DA rats may be associated with increased level of HMBG1 molecule in
the spleen. More pronounced proinflammatory response to oral Cd administration in gut
as well as in MLN and spleen of DA rats in comparison to AO rats (in which similar
concentrations of deposited Cd were found) show that DA rats are more susceptible to
oral subchronic administration of this metal.
The results of this study contribute to the understanding of the mechanisms
which underlie the toxic Cd effects on immune response in intestine, for the first time
showing the effect of this metal on homeostasis of innate and adaptive components of
immune response in MLN. At the same time, this study has also shown the significance
of tissue in expressing Cd toxicity. Also, for the first time, this study has indicated the
effect of genetic background on orally administered Cd effects, suggesting the
significance of careful selection of experimental animals to be used in the analysis of
immunotoxic effects of this metal.",
publisher = "Belgrade: University of Belgrade, Faculty of Biology",
journal = "University of Belgrade, Faculty of Biology",
title = "Intestinalni i sistemski imunski efekti oralnog unosa kadmijuma kod pacova, Intestinal and systemic immune effects
of oral cadmium intake in rats",
pages = "1-139",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_2517"
}

Ninkov, M.. (2016). Intestinalni i sistemski imunski efekti oralnog unosa kadmijuma kod pacova. in University of Belgrade, Faculty of Biology
Belgrade: University of Belgrade, Faculty of Biology., 1-139.
https://hdl.handle.net/21.15107/rcub_ibiss_2517

Ninkov M. Intestinalni i sistemski imunski efekti oralnog unosa kadmijuma kod pacova. in University of Belgrade, Faculty of Biology. 2016;:1-139.
https://hdl.handle.net/21.15107/rcub_ibiss_2517 .

Ninkov, Marina, "Intestinalni i sistemski imunski efekti oralnog unosa kadmijuma kod pacova" in University of Belgrade, Faculty of Biology (2016):1-139,
https://hdl.handle.net/21.15107/rcub_ibiss_2517 .

TY  - CONF
AU  - Ninkov, Marina
AU  - Popov Aleksandrov, Aleksandra
AU  - Demenesku, Jelena
AU  - Mirkov, Ivana
AU  - Mileusnić, Dina
AU  - Grigorov, Ilijana
AU  - Petrović, Anja
AU  - Zolotarevski, Lidija
AU  - Nikolic, Milica
AU  - Kataranovski, Milena
PY  - 2015
UR  - http://www.medf.kg.ac.rs/efis/Arandjelovac%20Abstract%20book%202015.pdf
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4811
AB  - Gastrointestinal (GI) tract is one of the main targets of cadmium (Cd),
important food and drinking water contaminant. In this study, the effect of
subchronic (30 days) oral (in drinking water) intake of environmentally
relevant doses of cadmium (5µg/ml and 50µg/ml) on intestinal [(tissue of
duodenum and mesenteric lymph node (mLN) cells)] was examined in
Dark Agouti (DA) rats. Atomic absorption spectrophotometry (AAS)
analysis revealed significant cadmium load in duodenum,which was
associated with changes of both intestinal bacterial load and composition
(Denaturing Gradient Gel Electrophoresis/DGGE).Shortening of villi,
damage to epithelium, increases in goblet-like vacuoles and mononuclear
cell infiltration in lamina propria were histologically evident at both
cadmium doses, with massive necrosis at higher Cd dose (judging by High
Mobility Group Box-1/HMGB-1 Western blot analysis).Increased levels of
proinflammatory cytokines (IL-1β, IFN-γ, IL-17) were observed at both Cd
doses (TNFα at higher dose solely). Cadmium administration affected
draining lymph nodes as well, judging by signs of stress response (drop of
cellular reduced glutathione/GSH at higher dose, rise of
metallothionein/MT mRNA at both doses).Increased cellularity of mLN
was observed at higher Cd dose, but with no changes in proliferative
responses. Intake of both Cd doses resulted in higher (compared to controls)
levels of IFN-γ and IL-17 mRNA as well as increased mLN cell
responsiveness to ConA stimulation.Significant increases in numbers of
CD68+ cells and stimulation of innate immune activities (numbers of
dihydrorhodamine/DHR+ cells and intracellular myeloperoxidase/MPO+
cells, LPS-stimulated nitric oxide/NO production and ex vivo IL-1β
expression) were observed at higher dose of cadmium.Proinflammatory
effects of cadmium might have resulted from changes in gut microbiota and
tissue damage.Interactions of this metal with intestinal immune system
should be taken into account when assessing dietary cadmium as health risk
factor.
PB  - Belgrade: Immunological Society of Serbia
C3  - 3rd Belgrade EFIS symposium on Immunoregulation: Immunity, Infection, Autoimmunity and Aging, May 24-27, 2015, Arandjelovac, Serbia
T1  - Subchronic oral intake of low cadmium doses affects intestinal immune responses in rats
SP  - 48
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4811
ER  - 

@conference{
editor = "Lukić, Miodrag, Jonjic, Stipan, Nikolich-Zugich, Janko",
author = "Ninkov, Marina and Popov Aleksandrov, Aleksandra and Demenesku, Jelena and Mirkov, Ivana and Mileusnić, Dina and Grigorov, Ilijana and Petrović, Anja and Zolotarevski, Lidija and Nikolic, Milica and Kataranovski, Milena",
year = "2015",
abstract = "Gastrointestinal (GI) tract is one of the main targets of cadmium (Cd),
important food and drinking water contaminant. In this study, the effect of
subchronic (30 days) oral (in drinking water) intake of environmentally
relevant doses of cadmium (5µg/ml and 50µg/ml) on intestinal [(tissue of
duodenum and mesenteric lymph node (mLN) cells)] was examined in
Dark Agouti (DA) rats. Atomic absorption spectrophotometry (AAS)
analysis revealed significant cadmium load in duodenum,which was
associated with changes of both intestinal bacterial load and composition
(Denaturing Gradient Gel Electrophoresis/DGGE).Shortening of villi,
damage to epithelium, increases in goblet-like vacuoles and mononuclear
cell infiltration in lamina propria were histologically evident at both
cadmium doses, with massive necrosis at higher Cd dose (judging by High
Mobility Group Box-1/HMGB-1 Western blot analysis).Increased levels of
proinflammatory cytokines (IL-1β, IFN-γ, IL-17) were observed at both Cd
doses (TNFα at higher dose solely). Cadmium administration affected
draining lymph nodes as well, judging by signs of stress response (drop of
cellular reduced glutathione/GSH at higher dose, rise of
metallothionein/MT mRNA at both doses).Increased cellularity of mLN
was observed at higher Cd dose, but with no changes in proliferative
responses. Intake of both Cd doses resulted in higher (compared to controls)
levels of IFN-γ and IL-17 mRNA as well as increased mLN cell
responsiveness to ConA stimulation.Significant increases in numbers of
CD68+ cells and stimulation of innate immune activities (numbers of
dihydrorhodamine/DHR+ cells and intracellular myeloperoxidase/MPO+
cells, LPS-stimulated nitric oxide/NO production and ex vivo IL-1β
expression) were observed at higher dose of cadmium.Proinflammatory
effects of cadmium might have resulted from changes in gut microbiota and
tissue damage.Interactions of this metal with intestinal immune system
should be taken into account when assessing dietary cadmium as health risk
factor.",
publisher = "Belgrade: Immunological Society of Serbia",
journal = "3rd Belgrade EFIS symposium on Immunoregulation: Immunity, Infection, Autoimmunity and Aging, May 24-27, 2015, Arandjelovac, Serbia",
title = "Subchronic oral intake of low cadmium doses affects intestinal immune responses in rats",
pages = "48",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4811"
}

Lukić, M., Jonjic, S., Nikolich-Zugich, J., Ninkov, M., Popov Aleksandrov, A., Demenesku, J., Mirkov, I., Mileusnić, D., Grigorov, I., Petrović, A., Zolotarevski, L., Nikolic, M.,& Kataranovski, M.. (2015). Subchronic oral intake of low cadmium doses affects intestinal immune responses in rats. in 3rd Belgrade EFIS symposium on Immunoregulation: Immunity, Infection, Autoimmunity and Aging, May 24-27, 2015, Arandjelovac, Serbia
Belgrade: Immunological Society of Serbia., 48.
https://hdl.handle.net/21.15107/rcub_ibiss_4811

Lukić M, Jonjic S, Nikolich-Zugich J, Ninkov M, Popov Aleksandrov A, Demenesku J, Mirkov I, Mileusnić D, Grigorov I, Petrović A, Zolotarevski L, Nikolic M, Kataranovski M. Subchronic oral intake of low cadmium doses affects intestinal immune responses in rats. in 3rd Belgrade EFIS symposium on Immunoregulation: Immunity, Infection, Autoimmunity and Aging, May 24-27, 2015, Arandjelovac, Serbia. 2015;:48.
https://hdl.handle.net/21.15107/rcub_ibiss_4811 .

Lukić, Miodrag, Jonjic, Stipan, Nikolich-Zugich, Janko, Ninkov, Marina, Popov Aleksandrov, Aleksandra, Demenesku, Jelena, Mirkov, Ivana, Mileusnić, Dina, Grigorov, Ilijana, Petrović, Anja, Zolotarevski, Lidija, Nikolic, Milica, Kataranovski, Milena, "Subchronic oral intake of low cadmium doses affects intestinal immune responses in rats" in 3rd Belgrade EFIS symposium on Immunoregulation: Immunity, Infection, Autoimmunity and Aging, May 24-27, 2015, Arandjelovac, Serbia (2015):48,
https://hdl.handle.net/21.15107/rcub_ibiss_4811 .

TY  - JOUR
AU  - Djokic, Jelena
AU  - Popov Aleksandrov, Aleksandra
AU  - Ninkov, Marina
AU  - Mirkov, Ivana
AU  - Zolotarevski, Lidija
AU  - Kataranovski, Dragan S.
AU  - Kataranovski, Milena
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1984
AB  - Although numerous investigations have demonstrated a direct effect of
   cadmium (Cd) on peripheral blood mononuclear cell (PBMC) activity in
   humans, there is virtually no data concerning the in vivo impact of this
   metal on circulatory mononuclear cells. In this study, the effects of a
   sub-lethal Cd (1 mg/kg) dose were examined in rats 48 h following a
   single intraperitoneal injection. Cd treatment resulted in increased
   total peripheral blood leukocyte levels; however, decreases in PBMC
   numbers were seen. These changes coincided with an accumulation of
   mononuclear cells in the lungs and an increase in mononuclear cells
   expressing CD11b. A lack of effect of Cd on spontaneous nitric oxide
   (NO) production and on iNOS mRNA levels in the PBMC was also noted.
   Differential effects of Cd on PBMC inflammatory cytokine (IL-1 beta, TNF
   alpha, IL-6, IFN gamma, and IL-17) gene expression and production were
   also seen. Specifically, except for IL-1 beta (levels increased), there
   were decreases (relative to controls) in mRNA levels for all the other
   cytokines examined. While there were no Cd treatment-related changes in
   spontaneous production of the cytokines assessed, there seemed to be a
   trend (p = 0.06) toward a decrease in spontaneous IL-6 release. When
   these harvested cells were stimulated ex vivo, there was no effect from
   Cd exposure on LPS-stimulated IL-1 beta and TNF alpha or on
   ConA-stimulated IFN gamma or IL-17 production, but a decrease in IL-6
   production in response to LPS was, again, noted. A preliminary study
   with a lower Cd dose (0.5 mg/kg) revealed some of the same outcomes
   noted here (mononuclear cell infiltration into lungs, increases in PBMC
   IL-1 beta mRNA levels), but differential (increased IL-17 mRNA levels)
   or newly detected outcomes (increased levels of IL-1 alpha mRNA) as
   well. The described effects of the single in vivo exposure to Cd on PBMC
   might contribute to a better overall understanding of the
   immunomodulatory potential of this environmental contaminant.
T2  - Journal Of Immunotoxicology
T1  - Cadmium administration affects circulatory mononuclear cells in rats
IS  - 2
VL  - 12
DO  - 10.3109/1547691X.2014.904955
SP  - 115
EP  - 123
ER  - 

@article{
author = "Djokic, Jelena and Popov Aleksandrov, Aleksandra and Ninkov, Marina and Mirkov, Ivana and Zolotarevski, Lidija and Kataranovski, Dragan S. and Kataranovski, Milena",
year = "2015",
abstract = "Although numerous investigations have demonstrated a direct effect of
   cadmium (Cd) on peripheral blood mononuclear cell (PBMC) activity in
   humans, there is virtually no data concerning the in vivo impact of this
   metal on circulatory mononuclear cells. In this study, the effects of a
   sub-lethal Cd (1 mg/kg) dose were examined in rats 48 h following a
   single intraperitoneal injection. Cd treatment resulted in increased
   total peripheral blood leukocyte levels; however, decreases in PBMC
   numbers were seen. These changes coincided with an accumulation of
   mononuclear cells in the lungs and an increase in mononuclear cells
   expressing CD11b. A lack of effect of Cd on spontaneous nitric oxide
   (NO) production and on iNOS mRNA levels in the PBMC was also noted.
   Differential effects of Cd on PBMC inflammatory cytokine (IL-1 beta, TNF
   alpha, IL-6, IFN gamma, and IL-17) gene expression and production were
   also seen. Specifically, except for IL-1 beta (levels increased), there
   were decreases (relative to controls) in mRNA levels for all the other
   cytokines examined. While there were no Cd treatment-related changes in
   spontaneous production of the cytokines assessed, there seemed to be a
   trend (p = 0.06) toward a decrease in spontaneous IL-6 release. When
   these harvested cells were stimulated ex vivo, there was no effect from
   Cd exposure on LPS-stimulated IL-1 beta and TNF alpha or on
   ConA-stimulated IFN gamma or IL-17 production, but a decrease in IL-6
   production in response to LPS was, again, noted. A preliminary study
   with a lower Cd dose (0.5 mg/kg) revealed some of the same outcomes
   noted here (mononuclear cell infiltration into lungs, increases in PBMC
   IL-1 beta mRNA levels), but differential (increased IL-17 mRNA levels)
   or newly detected outcomes (increased levels of IL-1 alpha mRNA) as
   well. The described effects of the single in vivo exposure to Cd on PBMC
   might contribute to a better overall understanding of the
   immunomodulatory potential of this environmental contaminant.",
journal = "Journal Of Immunotoxicology",
title = "Cadmium administration affects circulatory mononuclear cells in rats",
number = "2",
volume = "12",
doi = "10.3109/1547691X.2014.904955",
pages = "115-123"
}

Djokic, J., Popov Aleksandrov, A., Ninkov, M., Mirkov, I., Zolotarevski, L., Kataranovski, D. S.,& Kataranovski, M.. (2015). Cadmium administration affects circulatory mononuclear cells in rats. in Journal Of Immunotoxicology, 12(2), 115-123.
https://doi.org/10.3109/1547691X.2014.904955

Djokic J, Popov Aleksandrov A, Ninkov M, Mirkov I, Zolotarevski L, Kataranovski DS, Kataranovski M. Cadmium administration affects circulatory mononuclear cells in rats. in Journal Of Immunotoxicology. 2015;12(2):115-123.
doi:10.3109/1547691X.2014.904955 .

Djokic, Jelena, Popov Aleksandrov, Aleksandra, Ninkov, Marina, Mirkov, Ivana, Zolotarevski, Lidija, Kataranovski, Dragan S., Kataranovski, Milena, "Cadmium administration affects circulatory mononuclear cells in rats" in Journal Of Immunotoxicology, 12, no. 2 (2015):115-123,
https://doi.org/10.3109/1547691X.2014.904955 . .

TY  - JOUR
AU  - Ninkov, Marina
AU  - Popov Aleksandrov, Aleksandra
AU  - Demenesku, Jelena
AU  - Mirkov, Ivana
AU  - Tucović, Dina
AU  - Petrovic, Anja
AU  - Grigorov, Ilijana
AU  - Zolotarevski, Lidija
AU  - Tolinacki, Maja
AU  - Kataranovski, Dragan S.
AU  - Brceski, Ilija
AU  - Kataranovski, Milena
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2364
AB  - Gastrointestinal tract is one of the main targets of cadmium (Cd), an
   important food and drinking water contaminant. In the present study, the
   effect of subchronic (30 days) oral (in water) intake of 5ppm and 50ppm
   of cadmium on immune responses in the gut was examined in rats. Cadmium
   consumption resulted in reduction of bacteria corresponding to
   Lactobacillus strain, tissue damage and intestinal inflammation
   {[}increases in high mobility group box 1 (HMGB1 molecules), superoxide
   dismutase (SOD) and catalase (CAT) activity and proinflammatory cytokine
   (TNF, IL-1 beta, IFN-gamma, IL-17) content]. Draining (mesenteric) lymph
   node (MLN) stress response was observed {[}elevation of MLN glutathione
   (GSH) and metallothionein (MT) mRNA levels] and stimulation of both
   adaptive {[}cellularity, proliferation, proinflammatory (IFN-gamma and
   IL-17) MLN cell cytokine responses] as well as innate immune activity
   (increases in numbers of NK and CD68(+) cells, oxidative activities,
   IL-1 beta). In contrast to proinflammatory milieu in MLN, decreased or
   unchanged antiinflammatory IL-10 response was observed. Stimulation of
   immune activities of MLN cells have, most probably, resulted from
   sensing of cadmium-induced tissue injury, but also from bacterial
   antigens that breached compromised intestinal barrier. These effects of
   cadmium should be taken into account when assessing dietary cadmium as
   health risk factor. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
T2  - Toxicology Letters
T1  - Toxicity of oral cadmium intake: Impact on gut immunity
IS  - 2
VL  - 237
DO  - 10.1016/j.toxlet.2015.06.002
SP  - 89
EP  - 99
ER  - 

@article{
author = "Ninkov, Marina and Popov Aleksandrov, Aleksandra and Demenesku, Jelena and Mirkov, Ivana and Tucović, Dina and Petrovic, Anja and Grigorov, Ilijana and Zolotarevski, Lidija and Tolinacki, Maja and Kataranovski, Dragan S. and Brceski, Ilija and Kataranovski, Milena",
year = "2015",
abstract = "Gastrointestinal tract is one of the main targets of cadmium (Cd), an
   important food and drinking water contaminant. In the present study, the
   effect of subchronic (30 days) oral (in water) intake of 5ppm and 50ppm
   of cadmium on immune responses in the gut was examined in rats. Cadmium
   consumption resulted in reduction of bacteria corresponding to
   Lactobacillus strain, tissue damage and intestinal inflammation
   {[}increases in high mobility group box 1 (HMGB1 molecules), superoxide
   dismutase (SOD) and catalase (CAT) activity and proinflammatory cytokine
   (TNF, IL-1 beta, IFN-gamma, IL-17) content]. Draining (mesenteric) lymph
   node (MLN) stress response was observed {[}elevation of MLN glutathione
   (GSH) and metallothionein (MT) mRNA levels] and stimulation of both
   adaptive {[}cellularity, proliferation, proinflammatory (IFN-gamma and
   IL-17) MLN cell cytokine responses] as well as innate immune activity
   (increases in numbers of NK and CD68(+) cells, oxidative activities,
   IL-1 beta). In contrast to proinflammatory milieu in MLN, decreased or
   unchanged antiinflammatory IL-10 response was observed. Stimulation of
   immune activities of MLN cells have, most probably, resulted from
   sensing of cadmium-induced tissue injury, but also from bacterial
   antigens that breached compromised intestinal barrier. These effects of
   cadmium should be taken into account when assessing dietary cadmium as
   health risk factor. (C) 2015 Elsevier Ireland Ltd. All rights reserved.",
journal = "Toxicology Letters",
title = "Toxicity of oral cadmium intake: Impact on gut immunity",
number = "2",
volume = "237",
doi = "10.1016/j.toxlet.2015.06.002",
pages = "89-99"
}

Ninkov, M., Popov Aleksandrov, A., Demenesku, J., Mirkov, I., Tucović, D., Petrovic, A., Grigorov, I., Zolotarevski, L., Tolinacki, M., Kataranovski, D. S., Brceski, I.,& Kataranovski, M.. (2015). Toxicity of oral cadmium intake: Impact on gut immunity. in Toxicology Letters, 237(2), 89-99.
https://doi.org/10.1016/j.toxlet.2015.06.002

Ninkov M, Popov Aleksandrov A, Demenesku J, Mirkov I, Tucović D, Petrovic A, Grigorov I, Zolotarevski L, Tolinacki M, Kataranovski DS, Brceski I, Kataranovski M. Toxicity of oral cadmium intake: Impact on gut immunity. in Toxicology Letters. 2015;237(2):89-99.
doi:10.1016/j.toxlet.2015.06.002 .

Ninkov, Marina, Popov Aleksandrov, Aleksandra, Demenesku, Jelena, Mirkov, Ivana, Tucović, Dina, Petrovic, Anja, Grigorov, Ilijana, Zolotarevski, Lidija, Tolinacki, Maja, Kataranovski, Dragan S., Brceski, Ilija, Kataranovski, Milena, "Toxicity of oral cadmium intake: Impact on gut immunity" in Toxicology Letters, 237, no. 2 (2015):89-99,
https://doi.org/10.1016/j.toxlet.2015.06.002 . .