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  - 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  - 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  - 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  - 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 . .

TY  - JOUR
AU  - Mirkov, Ivana
AU  - Demenesku, Jelena
AU  - Popov Aleksandrov, Aleksandra
AU  - Ninkov, Marina
AU  - Glamočlija, Jasmina
AU  - Kataranovski, Dragan S.
AU  - Kataranovski, Milena
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1912
AB  - Although the relevance of genetically-based variations in susceptibility
   to pulmonary aspergillosis was shown in immunocompromised mice and is
   indicated in humans, there is virtually no information concerning
   variations in antifungal immune responses in resistant individuals. We
   have shown recently the relevance of proinflammatory cytokine
   (interferon-gamma/IFN-gamma and interleukin-17/IL-17) responses in
   resistance to sublethal Aspergillus fumigatus infection of
   non-suppressed Dark Agouti (DA) rats (strain known of a substantial
   immune reactivity to noxious insults). In this study, anti-fungal immune
   activities of leukocytes recovered from lungs by enzyme digestion
   (phagocytosis, oxidative activity, hyphal killing, CD11b expression, as
   well as production of IFN-gamma, IL-17 and Th2/anti-inflammatory
   cytokines interleukin-4/IL-4 and interleukin-10/IL-10) were investigated
   in less reactive Albino Oxford (AO) and compared to DA rats. Elimination
   of fungus from lungs of AO rats was associated with lower degree of
   leukocyte infiltration and of the majority of their basic effector
   activities in comparison to DA rats. Lower production of IFN-gamma by
   pulmonary leukocytes was observed early (day 1) post infection (p.i.) in
   AO compared to DA rats, but without changes in IL-4. Both strains
   responded to infection by an increase of IL-17 and IL-10, but production
   of cytokines was higher (from days 7 p.i. and 3 p.i. for IL-17 and
   IL-10, respectively) in AO compared to DA rats. The levels and pattern
   of IFN-gamma and IL-4 responses by draining lymph node (dLN) cells were
   similar in both strains and basically corresponded to those of lung
   leukocytes. In contrast, similar levels of draining lymph node cell
   production of IL-17 and IL-10 were observed in both strains with lack of
   changes in mRNA, what suggests additional stimulation of these cytokines
   in lungs of AO rats. The knowledge of strain differences in the
   immune-based strategies in response of immunocompetent hosts to A.
   fumigatus might contribute to our understanding of variations in
   underlying mechanisms that enable of resistance to this fungus. (C) 2015
   Elsevier GmbH. All rights reserved.
T2  - Immunobiology
T1  - Strain differences in the immune mechanisms of resistance of
 immunocompetent rats to pulmonary aspergillosis
IS  - 9
VL  - 220
DO  - 10.1016/j.imbio.2015.05.007
SP  - 1075
EP  - 1084
ER  - 

@article{
author = "Mirkov, Ivana and Demenesku, Jelena and Popov Aleksandrov, Aleksandra and Ninkov, Marina and Glamočlija, Jasmina and Kataranovski, Dragan S. and Kataranovski, Milena",
year = "2015",
abstract = "Although the relevance of genetically-based variations in susceptibility
   to pulmonary aspergillosis was shown in immunocompromised mice and is
   indicated in humans, there is virtually no information concerning
   variations in antifungal immune responses in resistant individuals. We
   have shown recently the relevance of proinflammatory cytokine
   (interferon-gamma/IFN-gamma and interleukin-17/IL-17) responses in
   resistance to sublethal Aspergillus fumigatus infection of
   non-suppressed Dark Agouti (DA) rats (strain known of a substantial
   immune reactivity to noxious insults). In this study, anti-fungal immune
   activities of leukocytes recovered from lungs by enzyme digestion
   (phagocytosis, oxidative activity, hyphal killing, CD11b expression, as
   well as production of IFN-gamma, IL-17 and Th2/anti-inflammatory
   cytokines interleukin-4/IL-4 and interleukin-10/IL-10) were investigated
   in less reactive Albino Oxford (AO) and compared to DA rats. Elimination
   of fungus from lungs of AO rats was associated with lower degree of
   leukocyte infiltration and of the majority of their basic effector
   activities in comparison to DA rats. Lower production of IFN-gamma by
   pulmonary leukocytes was observed early (day 1) post infection (p.i.) in
   AO compared to DA rats, but without changes in IL-4. Both strains
   responded to infection by an increase of IL-17 and IL-10, but production
   of cytokines was higher (from days 7 p.i. and 3 p.i. for IL-17 and
   IL-10, respectively) in AO compared to DA rats. The levels and pattern
   of IFN-gamma and IL-4 responses by draining lymph node (dLN) cells were
   similar in both strains and basically corresponded to those of lung
   leukocytes. In contrast, similar levels of draining lymph node cell
   production of IL-17 and IL-10 were observed in both strains with lack of
   changes in mRNA, what suggests additional stimulation of these cytokines
   in lungs of AO rats. The knowledge of strain differences in the
   immune-based strategies in response of immunocompetent hosts to A.
   fumigatus might contribute to our understanding of variations in
   underlying mechanisms that enable of resistance to this fungus. (C) 2015
   Elsevier GmbH. All rights reserved.",
journal = "Immunobiology",
title = "Strain differences in the immune mechanisms of resistance of
 immunocompetent rats to pulmonary aspergillosis",
number = "9",
volume = "220",
doi = "10.1016/j.imbio.2015.05.007",
pages = "1075-1084"
}

Mirkov, I., Demenesku, J., Popov Aleksandrov, A., Ninkov, M., Glamočlija, J., Kataranovski, D. S.,& Kataranovski, M.. (2015). Strain differences in the immune mechanisms of resistance of
 immunocompetent rats to pulmonary aspergillosis. in Immunobiology, 220(9), 1075-1084.
https://doi.org/10.1016/j.imbio.2015.05.007

Mirkov I, Demenesku J, Popov Aleksandrov A, Ninkov M, Glamočlija J, Kataranovski DS, Kataranovski M. Strain differences in the immune mechanisms of resistance of
 immunocompetent rats to pulmonary aspergillosis. in Immunobiology. 2015;220(9):1075-1084.
doi:10.1016/j.imbio.2015.05.007 .

Mirkov, Ivana, Demenesku, Jelena, Popov Aleksandrov, Aleksandra, Ninkov, Marina, Glamočlija, Jasmina, Kataranovski, Dragan S., Kataranovski, Milena, "Strain differences in the immune mechanisms of resistance of
 immunocompetent rats to pulmonary aspergillosis" in Immunobiology, 220, no. 9 (2015):1075-1084,
https://doi.org/10.1016/j.imbio.2015.05.007 . .

TY  - JOUR
AU  - Popov Aleksandrov, Aleksandra
AU  - Mirkov, Ivana
AU  - Demenesku, Jelena
AU  - Ninkov, Marina
AU  - Zolotarevski, Lidija
AU  - Kataranovski, Dragan S.
AU  - Kataranovski, Milena
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2092
AB  - Genetic factors are among the most important determinants of
   susceptibility to induction of allergic contact dermatitis. A limited
   number of studies of experimental contact hypersensitivity (CHS) in
   animals has shown differences in the severity of CHS; however, the
   underlying mechanisms are unknown. In this study comparative analysis of
   CHS to low and high dinitrochlorobenzene (DNCB) doses regimen of
   sensitization/challenge in inbred Dark Agouti (DA) and Albino Oxford
   (AO) rats was examined. Basic aspects of draining lymph node (dLN)
   activity (cellularity, proliferation), proinflammatory (IFN-gamma,
   IL-17) and anti-inflammatory (IL-10) cytokine gene expression and
   production, as well as IL-12 and IL-23 subunits mRNA expression, were
   examined in challenge and sensitization phase of CHS reaction. Lower
   (compared to DA) intensity of CHS in AO rats was associated with lack of
   (or negligible) dLN responses in challenge phase (ex vivo, hapten- or
   IL-2-stimulated cell proliferation and proinflammatory cytokine mRNA and
   production levels) but with lack of changes in IL-10 response. Less
   pronounced dLN activity of sensitized animals of this strain was
   observed as well. Higher proliferative activity and more pronounced
   proinflammatory cytokine response during challenge and sensitization
   phase suggest these activities as underlying mechanisms of higher
   susceptibility of DA rats to CHS response to DNCB. (C) 2014 Elsevier
   Ltd. All rights reserved.
T2  - Food and Chemical Toxicology
T1  - Strain differences in contact hypersensitivity reaction to
 dinitrochlorobenzene (DNCB) in rats
VL  - 75
DO  - 10.1016/j.fct.2014.11.010
SP  - 94
EP  - 103
ER  - 

@article{
author = "Popov Aleksandrov, Aleksandra and Mirkov, Ivana and Demenesku, Jelena and Ninkov, Marina and Zolotarevski, Lidija and Kataranovski, Dragan S. and Kataranovski, Milena",
year = "2015",
abstract = "Genetic factors are among the most important determinants of
   susceptibility to induction of allergic contact dermatitis. A limited
   number of studies of experimental contact hypersensitivity (CHS) in
   animals has shown differences in the severity of CHS; however, the
   underlying mechanisms are unknown. In this study comparative analysis of
   CHS to low and high dinitrochlorobenzene (DNCB) doses regimen of
   sensitization/challenge in inbred Dark Agouti (DA) and Albino Oxford
   (AO) rats was examined. Basic aspects of draining lymph node (dLN)
   activity (cellularity, proliferation), proinflammatory (IFN-gamma,
   IL-17) and anti-inflammatory (IL-10) cytokine gene expression and
   production, as well as IL-12 and IL-23 subunits mRNA expression, were
   examined in challenge and sensitization phase of CHS reaction. Lower
   (compared to DA) intensity of CHS in AO rats was associated with lack of
   (or negligible) dLN responses in challenge phase (ex vivo, hapten- or
   IL-2-stimulated cell proliferation and proinflammatory cytokine mRNA and
   production levels) but with lack of changes in IL-10 response. Less
   pronounced dLN activity of sensitized animals of this strain was
   observed as well. Higher proliferative activity and more pronounced
   proinflammatory cytokine response during challenge and sensitization
   phase suggest these activities as underlying mechanisms of higher
   susceptibility of DA rats to CHS response to DNCB. (C) 2014 Elsevier
   Ltd. All rights reserved.",
journal = "Food and Chemical Toxicology",
title = "Strain differences in contact hypersensitivity reaction to
 dinitrochlorobenzene (DNCB) in rats",
volume = "75",
doi = "10.1016/j.fct.2014.11.010",
pages = "94-103"
}

Popov Aleksandrov, A., Mirkov, I., Demenesku, J., Ninkov, M., Zolotarevski, L., Kataranovski, D. S.,& Kataranovski, M.. (2015). Strain differences in contact hypersensitivity reaction to
 dinitrochlorobenzene (DNCB) in rats. in Food and Chemical Toxicology, 75, 94-103.
https://doi.org/10.1016/j.fct.2014.11.010

Popov Aleksandrov A, Mirkov I, Demenesku J, Ninkov M, Zolotarevski L, Kataranovski DS, Kataranovski M. Strain differences in contact hypersensitivity reaction to
 dinitrochlorobenzene (DNCB) in rats. in Food and Chemical Toxicology. 2015;75:94-103.
doi:10.1016/j.fct.2014.11.010 .

Popov Aleksandrov, Aleksandra, Mirkov, Ivana, Demenesku, Jelena, Ninkov, Marina, Zolotarevski, Lidija, Kataranovski, Dragan S., Kataranovski, Milena, "Strain differences in contact hypersensitivity reaction to
 dinitrochlorobenzene (DNCB) in rats" in Food and Chemical Toxicology, 75 (2015):94-103,
https://doi.org/10.1016/j.fct.2014.11.010 . .

TY  - CONF
AU  - Demenesku, Jelena
AU  - Mirkov, Ivana
AU  - Ninkov, Marina
AU  - Popov Aleksandrov, Aleksandra
AU  - Zolotarevski, Lidija
AU  - Subota, Vesna
AU  - Mileusnić, Dina
AU  - Kataranovski, Dragan
AU  - Kataranovski, Milena
PY  - 2015
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4808
AB  - Introduction: Conflicting data (suppression, augmentation, no effect) exist concerning cadmium (Cd) effects on immune system depending on activity and tissue examined. This study
investigates responses to acute Cd intoxication in three compartments (peripheral blood, spleen and lungs) in Dark Agouti (DA) and Albino Oxford (AO) rats, which are differently
susceptible to variety of stimuli.
Materials and Methods: Systemic (IL-6, TNF, acute phase proteins) and tissue responses [cell stress (metallothionein/MT gene expression), CD11b expression, and cytokine (IFN-γ,
IL-17, IL-10) production and mRNA expression] were measured following intraperitoneal (1 mg/kg) Cd administration.
Results: Cd induces systemic inflammatory response with similar intensity in both rat strains. Increase in Cd spleen content and MT expression evident in both strains (higher in DA
compared to AO rats) was followed by increase in neutrophil infiltration and CD11b expression (with same intensity). Although in both strains Cd caused decreased IFN-γ, unchanged
IL-17 and lower IL-10 responsiveness (compared to respective control), decrease of IFN-γ was more intense in DA compared to AO rats. In lungs of both strains increased Cd deposition
and MT expression (higher in AO) as well as neutrophil infiltration and CD11b expression (greater in DA) was observed. While decreased IFN-γ was noted in both strains, lower IL-17
and IL-10 (vs. controls) were evident in DA rats solely.
Conclusions: Acute Cd intoxication exerts strain-related effects (both inflammatory and immunosuppressive) depending on tissue and activity investigated, but the effects are more
pronounced in DA rats.
PB  - European Federation of Immunological Societies
C3  - 4th European Congress of Immunology, September 6-9, 2015, Vienna, Austria, p 353.
T1  - Strain differences in sterile inflammation and immune suppression induced by acute cadmium administration in rats depend on the affected activity and tissue
SP  - 353
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4808
ER  - 

@conference{
author = "Demenesku, Jelena and Mirkov, Ivana and Ninkov, Marina and Popov Aleksandrov, Aleksandra and Zolotarevski, Lidija and Subota, Vesna and Mileusnić, Dina and Kataranovski, Dragan and Kataranovski, Milena",
year = "2015",
abstract = "Introduction: Conflicting data (suppression, augmentation, no effect) exist concerning cadmium (Cd) effects on immune system depending on activity and tissue examined. This study
investigates responses to acute Cd intoxication in three compartments (peripheral blood, spleen and lungs) in Dark Agouti (DA) and Albino Oxford (AO) rats, which are differently
susceptible to variety of stimuli.
Materials and Methods: Systemic (IL-6, TNF, acute phase proteins) and tissue responses [cell stress (metallothionein/MT gene expression), CD11b expression, and cytokine (IFN-γ,
IL-17, IL-10) production and mRNA expression] were measured following intraperitoneal (1 mg/kg) Cd administration.
Results: Cd induces systemic inflammatory response with similar intensity in both rat strains. Increase in Cd spleen content and MT expression evident in both strains (higher in DA
compared to AO rats) was followed by increase in neutrophil infiltration and CD11b expression (with same intensity). Although in both strains Cd caused decreased IFN-γ, unchanged
IL-17 and lower IL-10 responsiveness (compared to respective control), decrease of IFN-γ was more intense in DA compared to AO rats. In lungs of both strains increased Cd deposition
and MT expression (higher in AO) as well as neutrophil infiltration and CD11b expression (greater in DA) was observed. While decreased IFN-γ was noted in both strains, lower IL-17
and IL-10 (vs. controls) were evident in DA rats solely.
Conclusions: Acute Cd intoxication exerts strain-related effects (both inflammatory and immunosuppressive) depending on tissue and activity investigated, but the effects are more
pronounced in DA rats.",
publisher = "European Federation of Immunological Societies",
journal = "4th European Congress of Immunology, September 6-9, 2015, Vienna, Austria, p 353.",
title = "Strain differences in sterile inflammation and immune suppression induced by acute cadmium administration in rats depend on the affected activity and tissue",
pages = "353",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4808"
}

Demenesku, J., Mirkov, I., Ninkov, M., Popov Aleksandrov, A., Zolotarevski, L., Subota, V., Mileusnić, D., Kataranovski, D.,& Kataranovski, M.. (2015). Strain differences in sterile inflammation and immune suppression induced by acute cadmium administration in rats depend on the affected activity and tissue. in 4th European Congress of Immunology, September 6-9, 2015, Vienna, Austria, p 353.
European Federation of Immunological Societies., 353.
https://hdl.handle.net/21.15107/rcub_ibiss_4808

Demenesku J, Mirkov I, Ninkov M, Popov Aleksandrov A, Zolotarevski L, Subota V, Mileusnić D, Kataranovski D, Kataranovski M. Strain differences in sterile inflammation and immune suppression induced by acute cadmium administration in rats depend on the affected activity and tissue. in 4th European Congress of Immunology, September 6-9, 2015, Vienna, Austria, p 353.. 2015;:353.
https://hdl.handle.net/21.15107/rcub_ibiss_4808 .

Demenesku, Jelena, Mirkov, Ivana, Ninkov, Marina, Popov Aleksandrov, Aleksandra, Zolotarevski, Lidija, Subota, Vesna, Mileusnić, Dina, Kataranovski, Dragan, Kataranovski, Milena, "Strain differences in sterile inflammation and immune suppression induced by acute cadmium administration in rats depend on the affected activity and tissue" in 4th European Congress of Immunology, September 6-9, 2015, Vienna, Austria, p 353. (2015):353,
https://hdl.handle.net/21.15107/rcub_ibiss_4808 .

TY  - CONF
AU  - Ninkov, Marina
AU  - Popov Aleksandrov, Aleksandra
AU  - Demenesku, Jelena
AU  - Mirkov, Ivana
AU  - Mileusnić, Dina
AU  - Tolinacki, Maja
AU  - Zolotarevski, Lidija
AU  - Kataranovski, Dragan
AU  - Brceski, Ilija
AU  - Kataranovski, Milena
PY  - 2015
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4809
AB  - Introduction: Toxic metal cadmium (Cd) is important food and drinking water contaminant. The majority of ingested cadmium retained in the gastrointestinal tract (GIT) mucosa
which allocates GIT as its main target. Mechanisms of induction of intestinal inflammatory response are largely unknown.
Materials and Methods: Effect of subchronic (30 days) oral (in water) cadmium administration (5 ppm and 50 ppm) was examined in Dark Agouti (DA) and Albino Oxford (AO) rats.
Beside intestinal immune response, activity of draining mesenteric lymph node (MLN) cells, central place for induction of intestinal immune tolerance and local protective responses,
was evaluated.
Results: In both rat strains cadmium consumption resulted in reduction of bacteria (Lactobacillus strain), intestinal tissue damage, modulated antioxidant enzymes activity and
inflammation [increased proinflammatory cytokine (TNF, IL-1β, IFN-γ, IL-17) content in DA rats; increased TNF and IL-10 content in AO rats] in duodenal homogenates. Accumulation
of cadmium in MLN was followed by stress response [elevation of MLN glutathione and metallothionein mRNA levels] only in DA rats. Stimulation of both adaptive (proliferation, Th1
and Th17 cytokine response) and innate immune activities (NKG2D+, CD68+ cells, selected oxidative activities, IL-1β) in MLN was observed, more pronounced in DA compared to AO
rats.
Conclusions: Oral intake of cadmium resulted in intestinal damage, inflammation, and induction of proinflammatory milleu and innate effector cell activities in MLN. Cadmiuminduced proinflammatory responses in DA rats but discrete immune responses of AO rats imply strain-dependent effects of oral cadmium administration.
PB  - European Federation of Immunological Societies
C3  - 4th European Congress of Immunology, September 6-9, 2015, Vienna, Austria, p 486.
T1  - Oral cadmium intake and immune responses in the gut: intestinal inflammation and immune priming of mesenteric lymph nodes
SP  - 486
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4809
ER  - 

@conference{
author = "Ninkov, Marina and Popov Aleksandrov, Aleksandra and Demenesku, Jelena and Mirkov, Ivana and Mileusnić, Dina and Tolinacki, Maja and Zolotarevski, Lidija and Kataranovski, Dragan and Brceski, Ilija and Kataranovski, Milena",
year = "2015",
abstract = "Introduction: Toxic metal cadmium (Cd) is important food and drinking water contaminant. The majority of ingested cadmium retained in the gastrointestinal tract (GIT) mucosa
which allocates GIT as its main target. Mechanisms of induction of intestinal inflammatory response are largely unknown.
Materials and Methods: Effect of subchronic (30 days) oral (in water) cadmium administration (5 ppm and 50 ppm) was examined in Dark Agouti (DA) and Albino Oxford (AO) rats.
Beside intestinal immune response, activity of draining mesenteric lymph node (MLN) cells, central place for induction of intestinal immune tolerance and local protective responses,
was evaluated.
Results: In both rat strains cadmium consumption resulted in reduction of bacteria (Lactobacillus strain), intestinal tissue damage, modulated antioxidant enzymes activity and
inflammation [increased proinflammatory cytokine (TNF, IL-1β, IFN-γ, IL-17) content in DA rats; increased TNF and IL-10 content in AO rats] in duodenal homogenates. Accumulation
of cadmium in MLN was followed by stress response [elevation of MLN glutathione and metallothionein mRNA levels] only in DA rats. Stimulation of both adaptive (proliferation, Th1
and Th17 cytokine response) and innate immune activities (NKG2D+, CD68+ cells, selected oxidative activities, IL-1β) in MLN was observed, more pronounced in DA compared to AO
rats.
Conclusions: Oral intake of cadmium resulted in intestinal damage, inflammation, and induction of proinflammatory milleu and innate effector cell activities in MLN. Cadmiuminduced proinflammatory responses in DA rats but discrete immune responses of AO rats imply strain-dependent effects of oral cadmium administration.",
publisher = "European Federation of Immunological Societies",
journal = "4th European Congress of Immunology, September 6-9, 2015, Vienna, Austria, p 486.",
title = "Oral cadmium intake and immune responses in the gut: intestinal inflammation and immune priming of mesenteric lymph nodes",
pages = "486",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4809"
}

Ninkov, M., Popov Aleksandrov, A., Demenesku, J., Mirkov, I., Mileusnić, D., Tolinacki, M., Zolotarevski, L., Kataranovski, D., Brceski, I.,& Kataranovski, M.. (2015). Oral cadmium intake and immune responses in the gut: intestinal inflammation and immune priming of mesenteric lymph nodes. in 4th European Congress of Immunology, September 6-9, 2015, Vienna, Austria, p 486.
European Federation of Immunological Societies., 486.
https://hdl.handle.net/21.15107/rcub_ibiss_4809

Ninkov M, Popov Aleksandrov A, Demenesku J, Mirkov I, Mileusnić D, Tolinacki M, Zolotarevski L, Kataranovski D, Brceski I, Kataranovski M. Oral cadmium intake and immune responses in the gut: intestinal inflammation and immune priming of mesenteric lymph nodes. in 4th European Congress of Immunology, September 6-9, 2015, Vienna, Austria, p 486.. 2015;:486.
https://hdl.handle.net/21.15107/rcub_ibiss_4809 .

Ninkov, Marina, Popov Aleksandrov, Aleksandra, Demenesku, Jelena, Mirkov, Ivana, Mileusnić, Dina, Tolinacki, Maja, Zolotarevski, Lidija, Kataranovski, Dragan, Brceski, Ilija, Kataranovski, Milena, "Oral cadmium intake and immune responses in the gut: intestinal inflammation and immune priming of mesenteric lymph nodes" in 4th European Congress of Immunology, September 6-9, 2015, Vienna, Austria, p 486. (2015):486,
https://hdl.handle.net/21.15107/rcub_ibiss_4809 .

TY  - CONF
AU  - Demenesku, Jelena
AU  - Ninkov, Marina
AU  - Popov Aleksandrov, Aleksandra
AU  - Mirkov, Ivana
AU  - Mileusnić, Dina
AU  - Zolotarevski, Lidija
AU  - Tolinački, Maja
AU  - Kataranovski, Dragan
AU  - Brceski, Ilija
AU  - Kataranovski, Milena
PY  - 2015
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4810
AB  - Conflicting data exist concerning cadmium
effects on immune system depending on the
experimental model, exposure or tissue/activity
examined. In this study immunotoxicity of acute
intraperitoneal and oral cadmium
administration was investigated in rats. The
use of the inflammation-prone inbred Dark
Agouti (DA) and less reactive Albino Oxford
(AO) rats showed differential (immune activityrelated and/or strain-related) effects of
cadmium (1 mg of Cd/kg, i.p.) on spleen
immune responses. A decrease in ConAinduced proliferation (related to altered spleen
cells responsiveness to IL-2) and of IFN-γ
(independently of IL-4 and IL-10) was more
pronounced in DA rats. Increased innate
immunity splenocyte activity (granulocyte
CD11b+ cells, iNOS mRNA and NO
production, myeloperoxidase MPO activity, IL1β mRNA and IL-1β protein product levels)
were observed in both strains (some of them
more pronounced in DA rats), while a decrease
in respiratory burst (dihydrorhodamine/DHR
oxidation) was similar. 30-day oral intake of 5
ppm and 50 ppm of cadmium by DA rats
resulted in reduction of some probiotic bacteria,
villous damage and intestinal inflammation
[(increased levels of High Mobility Group
Box1/HMGB1, antioxidant enzyme (superoxide
dismutase/SOD and catalase/CAT) activity and
proinflammatory cytokine (TNF, IL-1β, IFN-γ,
IL-17) in gut homogenates]. Stimulation of both
adaptive (increased cellularity, proliferation,
IFN-γ and IL-17cytokine responses) as well as
innate immune activity (increases in numbers
of NK cells and M1-like macrophages,
oxidative cell activities, IL-1β) of gut draining
(mesenteric) lymph nodes was associated with
decreased or unchanged antiinflammatory
cytokine (IL-10) cell response. Differential
(immunosuppressive and immunostimulatory)
effects noted in the same tissue (spleen)
should be taken into account when exploring
immunotoxicity of this metal. Stimulation of gut
immune responses imply dietary cadmium as
health risk factor.
PB  - Department of Biomedical Sciences-Histology of the University of Sassari
C3  - II Cadmium Symposium, June 25-27, 2015, Sassari, Italy
T1  - Immunotoxicology of cadmium: Insight from acute intraperitoneal and intermediate period of oral exposure of rats
SP  - 31
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4810
ER  - 

@conference{
author = "Demenesku, Jelena and Ninkov, Marina and Popov Aleksandrov, Aleksandra and Mirkov, Ivana and Mileusnić, Dina and Zolotarevski, Lidija and Tolinački, Maja and Kataranovski, Dragan and Brceski, Ilija and Kataranovski, Milena",
year = "2015",
abstract = "Conflicting data exist concerning cadmium
effects on immune system depending on the
experimental model, exposure or tissue/activity
examined. In this study immunotoxicity of acute
intraperitoneal and oral cadmium
administration was investigated in rats. The
use of the inflammation-prone inbred Dark
Agouti (DA) and less reactive Albino Oxford
(AO) rats showed differential (immune activityrelated and/or strain-related) effects of
cadmium (1 mg of Cd/kg, i.p.) on spleen
immune responses. A decrease in ConAinduced proliferation (related to altered spleen
cells responsiveness to IL-2) and of IFN-γ
(independently of IL-4 and IL-10) was more
pronounced in DA rats. Increased innate
immunity splenocyte activity (granulocyte
CD11b+ cells, iNOS mRNA and NO
production, myeloperoxidase MPO activity, IL1β mRNA and IL-1β protein product levels)
were observed in both strains (some of them
more pronounced in DA rats), while a decrease
in respiratory burst (dihydrorhodamine/DHR
oxidation) was similar. 30-day oral intake of 5
ppm and 50 ppm of cadmium by DA rats
resulted in reduction of some probiotic bacteria,
villous damage and intestinal inflammation
[(increased levels of High Mobility Group
Box1/HMGB1, antioxidant enzyme (superoxide
dismutase/SOD and catalase/CAT) activity and
proinflammatory cytokine (TNF, IL-1β, IFN-γ,
IL-17) in gut homogenates]. Stimulation of both
adaptive (increased cellularity, proliferation,
IFN-γ and IL-17cytokine responses) as well as
innate immune activity (increases in numbers
of NK cells and M1-like macrophages,
oxidative cell activities, IL-1β) of gut draining
(mesenteric) lymph nodes was associated with
decreased or unchanged antiinflammatory
cytokine (IL-10) cell response. Differential
(immunosuppressive and immunostimulatory)
effects noted in the same tissue (spleen)
should be taken into account when exploring
immunotoxicity of this metal. Stimulation of gut
immune responses imply dietary cadmium as
health risk factor.",
publisher = "Department of Biomedical Sciences-Histology of the University of Sassari",
journal = "II Cadmium Symposium, June 25-27, 2015, Sassari, Italy",
title = "Immunotoxicology of cadmium: Insight from acute intraperitoneal and intermediate period of oral exposure of rats",
pages = "31",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4810"
}

Demenesku, J., Ninkov, M., Popov Aleksandrov, A., Mirkov, I., Mileusnić, D., Zolotarevski, L., Tolinački, M., Kataranovski, D., Brceski, I.,& Kataranovski, M.. (2015). Immunotoxicology of cadmium: Insight from acute intraperitoneal and intermediate period of oral exposure of rats. in II Cadmium Symposium, June 25-27, 2015, Sassari, Italy
Department of Biomedical Sciences-Histology of the University of Sassari., 31.
https://hdl.handle.net/21.15107/rcub_ibiss_4810

Demenesku J, Ninkov M, Popov Aleksandrov A, Mirkov I, Mileusnić D, Zolotarevski L, Tolinački M, Kataranovski D, Brceski I, Kataranovski M. Immunotoxicology of cadmium: Insight from acute intraperitoneal and intermediate period of oral exposure of rats. in II Cadmium Symposium, June 25-27, 2015, Sassari, Italy. 2015;:31.
https://hdl.handle.net/21.15107/rcub_ibiss_4810 .

Demenesku, Jelena, Ninkov, Marina, Popov Aleksandrov, Aleksandra, Mirkov, Ivana, Mileusnić, Dina, Zolotarevski, Lidija, Tolinački, Maja, Kataranovski, Dragan, Brceski, Ilija, Kataranovski, Milena, "Immunotoxicology of cadmium: Insight from acute intraperitoneal and intermediate period of oral exposure of rats" in II Cadmium Symposium, June 25-27, 2015, Sassari, Italy (2015):31,
https://hdl.handle.net/21.15107/rcub_ibiss_4810 .

TY  - CONF
AU  - Popov Aleksandrov, Aleksandra
AU  - Mirkov, Ivana
AU  - Demenesku, Jelena
AU  - Ninkov, Marina
AU  - Mileusnić, Dina
AU  - Jovanovic, Jelena
AU  - Kataranovski, Dragan
AU  - Kataranovski, Milena
PY  - 2015
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4807
AB  - Introduction: Contact hypersensitivity (CHS) is animal model of allergic contact dermatitis, common skin inflammatory disease. Although mechanisms of CHS are much studied,
systemic effects in challenge phase are far less known.
Materials and methods: Parameters of adaptive and innate/inflammatory reaction were examined locally (ear skin cells) and systemically [peripheral blood mononuclear cells (PBMC)
and spleen cells] 24 hours after challenge, in two rat strains, Dark Agouti (DA) and Albino Oxford (AO), previously shown to differ in intensity of ear swelling response and draining
lymph node cell activity in CHS.
Results: While production of IL-17 by ear skin cells after challenge was increased in both rat strains (vs. controls), production of IFN-γ and CD8+ cell number was increased only in DA.
Activity relevant for innate immunity (CD11b+ skin cell number and NO production) was significantly increased only in DA. Production of proinflammatory cytokines TNF-α and IL-1β
by these cells was unchanged in both strains. Similarly to ear skin cells, IL-17 production by PBMC was increased in both strains while IFN-γ, and TNF-α, IL-1β and NO, only in DA. In
the spleen, however, only IFN-γ production was increased in both strains, while other parameters were variably affected in DA and AO.
Conclusion: In CHS reaction to dinitrochlorobenzene proinflammatory/effector activity detected locally in skin, coincides with PBMC activity (more pronounced in DA compared to AO
rats). Systemic effect was compartment dependent, given differential activity of spleen cells in two strains.
PB  - European Federation of Immunological Societies
C3  - 4th European Congress of Immunology, September 6-9, 2015, Vienna, Austria
T1  - Contact hypersensitivity to dinitrochlorobenzene induces systemic immunomodulatory effects that are strain-dependent
SP  - 130
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4807
ER  - 

@conference{
author = "Popov Aleksandrov, Aleksandra and Mirkov, Ivana and Demenesku, Jelena and Ninkov, Marina and Mileusnić, Dina and Jovanovic, Jelena and Kataranovski, Dragan and Kataranovski, Milena",
year = "2015",
abstract = "Introduction: Contact hypersensitivity (CHS) is animal model of allergic contact dermatitis, common skin inflammatory disease. Although mechanisms of CHS are much studied,
systemic effects in challenge phase are far less known.
Materials and methods: Parameters of adaptive and innate/inflammatory reaction were examined locally (ear skin cells) and systemically [peripheral blood mononuclear cells (PBMC)
and spleen cells] 24 hours after challenge, in two rat strains, Dark Agouti (DA) and Albino Oxford (AO), previously shown to differ in intensity of ear swelling response and draining
lymph node cell activity in CHS.
Results: While production of IL-17 by ear skin cells after challenge was increased in both rat strains (vs. controls), production of IFN-γ and CD8+ cell number was increased only in DA.
Activity relevant for innate immunity (CD11b+ skin cell number and NO production) was significantly increased only in DA. Production of proinflammatory cytokines TNF-α and IL-1β
by these cells was unchanged in both strains. Similarly to ear skin cells, IL-17 production by PBMC was increased in both strains while IFN-γ, and TNF-α, IL-1β and NO, only in DA. In
the spleen, however, only IFN-γ production was increased in both strains, while other parameters were variably affected in DA and AO.
Conclusion: In CHS reaction to dinitrochlorobenzene proinflammatory/effector activity detected locally in skin, coincides with PBMC activity (more pronounced in DA compared to AO
rats). Systemic effect was compartment dependent, given differential activity of spleen cells in two strains.",
publisher = "European Federation of Immunological Societies",
journal = "4th European Congress of Immunology, September 6-9, 2015, Vienna, Austria",
title = "Contact hypersensitivity to dinitrochlorobenzene induces systemic immunomodulatory effects that are strain-dependent",
pages = "130",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4807"
}

Popov Aleksandrov, A., Mirkov, I., Demenesku, J., Ninkov, M., Mileusnić, D., Jovanovic, J., Kataranovski, D.,& Kataranovski, M.. (2015). Contact hypersensitivity to dinitrochlorobenzene induces systemic immunomodulatory effects that are strain-dependent. in 4th European Congress of Immunology, September 6-9, 2015, Vienna, Austria
European Federation of Immunological Societies., 130.
https://hdl.handle.net/21.15107/rcub_ibiss_4807

Popov Aleksandrov A, Mirkov I, Demenesku J, Ninkov M, Mileusnić D, Jovanovic J, Kataranovski D, Kataranovski M. Contact hypersensitivity to dinitrochlorobenzene induces systemic immunomodulatory effects that are strain-dependent. in 4th European Congress of Immunology, September 6-9, 2015, Vienna, Austria. 2015;:130.
https://hdl.handle.net/21.15107/rcub_ibiss_4807 .

Popov Aleksandrov, Aleksandra, Mirkov, Ivana, Demenesku, Jelena, Ninkov, Marina, Mileusnić, Dina, Jovanovic, Jelena, Kataranovski, Dragan, Kataranovski, Milena, "Contact hypersensitivity to dinitrochlorobenzene induces systemic immunomodulatory effects that are strain-dependent" in 4th European Congress of Immunology, September 6-9, 2015, Vienna, Austria (2015):130,
https://hdl.handle.net/21.15107/rcub_ibiss_4807 .

TY  - JOUR
AU  - Demenesku, Jelena
AU  - Mirkov, Ivana
AU  - Ninkov, Marina
AU  - Popov Aleksandrov, Aleksandra
AU  - Zolotarevski, Lidija
AU  - Kataranovski, Dragan S.
AU  - Kataranovski, Milena
PY  - 2014
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2103
AB  - Conflicting data (both suppression and augmentation as well as lack of
   the effect) exist in respect to cadmium (Cd) and splenic T cell-based
   immune cell activity. Spleen is also the site of innate immune responses
   but impact of Cd on this type of immunity has been less explored. In the
   present study the effects of acute Cd administration on basic aspects of
   both T cell-based and innate immune spleen cell activity were examined
   in rats. Intraperitoneal injection of 1 mg of Cd/kg resulted in decrease
   in concanavalin A (ConA) induced proliferation which seems to be more
   related to altered spleen cells responsiveness to IL-2 than to
   apoptosis. Differential effects on proinflammatory T cell derived
   cytokines were observed (decreases of IFN-gamma gene expression and
   ConA-stimulated production, but increases in IL-17 mRNA levels with no
   effect on concentrations of protein product). Reduction of IFN-gamma
   production seemed not to rely on IL-4 and IL-10, but at least partly on
   nitric oxide (NO). Increased activity relevant for innate immunity
   (granulocyte and CD11b(+) cell accumulation in the spleen, inducible
   nitric oxide synthase/iNOS expression and NO production by spleen cells)
   was observed, but there was a decrease in respiratory burst
   (dihydrorhodamine/DHR oxidation and nitroblue tetrazolium/NBT
   reduction). Increases of TNF-alpha and IL-1 beta gene expression and
   IL-1 beta protein product were noted as well. Administration of 0.5 mg
   Cd/kg resulted in less pronounced (ConA-induced proliferation) or lack
   of the effect (IFN-gamma production) on spleen T cell activities and on
   innate activities (granulocyte accumulation, NO production) as well.
   However, increases of spleen cell respiratory burst activity and IL-1
   beta production were observed. Effects of lower cadmium doses (5 ppm and
   50 ppm) on several aspects of spleen cell immune activity were observed
   in intermediate period of exposure (30 days, oral intake) as well.
   Differential effects of Cd on immune activities of spleen cells might
   contribute to our understanding of the complexity of immunomodulatory
   effects of this metal. (C) 2014 Elsevier Ireland Ltd. All rights
   reserved.
T2  - Toxicology
T1  - Acute cadmium administration to rats exerts both immunosuppressive and
 proinflammatory effects in spleen
VL  - 326
DO  - 10.1016/j.tox.2014.10.012
SP  - 96
EP  - 108
ER  - 

@article{
author = "Demenesku, Jelena and Mirkov, Ivana and Ninkov, Marina and Popov Aleksandrov, Aleksandra and Zolotarevski, Lidija and Kataranovski, Dragan S. and Kataranovski, Milena",
year = "2014",
abstract = "Conflicting data (both suppression and augmentation as well as lack of
   the effect) exist in respect to cadmium (Cd) and splenic T cell-based
   immune cell activity. Spleen is also the site of innate immune responses
   but impact of Cd on this type of immunity has been less explored. In the
   present study the effects of acute Cd administration on basic aspects of
   both T cell-based and innate immune spleen cell activity were examined
   in rats. Intraperitoneal injection of 1 mg of Cd/kg resulted in decrease
   in concanavalin A (ConA) induced proliferation which seems to be more
   related to altered spleen cells responsiveness to IL-2 than to
   apoptosis. Differential effects on proinflammatory T cell derived
   cytokines were observed (decreases of IFN-gamma gene expression and
   ConA-stimulated production, but increases in IL-17 mRNA levels with no
   effect on concentrations of protein product). Reduction of IFN-gamma
   production seemed not to rely on IL-4 and IL-10, but at least partly on
   nitric oxide (NO). Increased activity relevant for innate immunity
   (granulocyte and CD11b(+) cell accumulation in the spleen, inducible
   nitric oxide synthase/iNOS expression and NO production by spleen cells)
   was observed, but there was a decrease in respiratory burst
   (dihydrorhodamine/DHR oxidation and nitroblue tetrazolium/NBT
   reduction). Increases of TNF-alpha and IL-1 beta gene expression and
   IL-1 beta protein product were noted as well. Administration of 0.5 mg
   Cd/kg resulted in less pronounced (ConA-induced proliferation) or lack
   of the effect (IFN-gamma production) on spleen T cell activities and on
   innate activities (granulocyte accumulation, NO production) as well.
   However, increases of spleen cell respiratory burst activity and IL-1
   beta production were observed. Effects of lower cadmium doses (5 ppm and
   50 ppm) on several aspects of spleen cell immune activity were observed
   in intermediate period of exposure (30 days, oral intake) as well.
   Differential effects of Cd on immune activities of spleen cells might
   contribute to our understanding of the complexity of immunomodulatory
   effects of this metal. (C) 2014 Elsevier Ireland Ltd. All rights
   reserved.",
journal = "Toxicology",
title = "Acute cadmium administration to rats exerts both immunosuppressive and
 proinflammatory effects in spleen",
volume = "326",
doi = "10.1016/j.tox.2014.10.012",
pages = "96-108"
}

Demenesku, J., Mirkov, I., Ninkov, M., Popov Aleksandrov, A., Zolotarevski, L., Kataranovski, D. S.,& Kataranovski, M.. (2014). Acute cadmium administration to rats exerts both immunosuppressive and
 proinflammatory effects in spleen. in Toxicology, 326, 96-108.
https://doi.org/10.1016/j.tox.2014.10.012

Demenesku J, Mirkov I, Ninkov M, Popov Aleksandrov A, Zolotarevski L, Kataranovski DS, Kataranovski M. Acute cadmium administration to rats exerts both immunosuppressive and
 proinflammatory effects in spleen. in Toxicology. 2014;326:96-108.
doi:10.1016/j.tox.2014.10.012 .

Demenesku, Jelena, Mirkov, Ivana, Ninkov, Marina, Popov Aleksandrov, Aleksandra, Zolotarevski, Lidija, Kataranovski, Dragan S., Kataranovski, Milena, "Acute cadmium administration to rats exerts both immunosuppressive and
 proinflammatory effects in spleen" in Toxicology, 326 (2014):96-108,
https://doi.org/10.1016/j.tox.2014.10.012 . .