TY  - JOUR
AU  - Trifunović, Svetlana
AU  - Šošić-Jurjević, Branka 
AU  - Ristić, Nataša
AU  - Nestorović, Nataša
AU  - Filipović, Branko
AU  - Stevanović, Ivana
AU  - Begović-Kuprešanin, Vesna
AU  - Manojlović-Stojanoski, Milica
PY  - 2023
UR  - https://www.mdpi.com/1422-0067/24/1/540
UR  - http://www.ncbi.nlm.nih.gov/pubmed/36613982
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC9820254
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5402
AB  - As the mediator between the mother and fetus, the placenta allows the most appropriate environment and optimal fetal growth. The placenta of one sex sometimes has a greater ability over the other to respond to and protect against possible maternal insults. Here, we characterized sex differences in the placenta's morphological features and antioxidant status following dexamethasone (Dx) exposure. Pregnant rats were exposed to Dx or saline. The placenta was histologically and stereologically analyzed. The activity of the antioxidant enzymes, lipid peroxides (TBARS), superoxide anion and nitric oxide (NO) was measured. The decrease in placental zone volumes was more pronounced (p < 0.05) in female placentas. The volume density of PCNA-immunopositive nuclei was reduced (p < 0.05) in both sexes. The reduced (p < 0.05) antioxidant enzyme activities, enhanced TBARS and NO concentration indicate that Dx exposure triggered oxidative stress in the placenta of both fetal sexes, albeit stronger in the placenta of female fetuses. In conclusion, maternal Dx treatment reduced the size and volume of placental zones, altered placental histomorphology, decreased cell proliferation and triggered oxidative stress; however, the placentas of female fetuses exerted more significant responses to the treatment effects. The reduced placental size most probably reduced the transport of nutrients and oxygen, thus resulting in the reduced weight of fetuses, similar in both sexes. The lesser ability of the male placenta to detect and react to maternal exposure to environmental challenges may lead to long-standing health effects.
PB  - Basel: MDPI
T2  - International Journal of Molecular Sciences
T1  - Maternal Dexamethasone Exposure Induces Sex-Specific Changes in Histomorphology and Redox Homeostasis of Rat Placenta
IS  - 1
VL  - 24
DO  - 10.3390/ijms24010540
SP  - 540
ER  - 

@article{
author = "Trifunović, Svetlana and Šošić-Jurjević, Branka  and Ristić, Nataša and Nestorović, Nataša and Filipović, Branko and Stevanović, Ivana and Begović-Kuprešanin, Vesna and Manojlović-Stojanoski, Milica",
year = "2023",
abstract = "As the mediator between the mother and fetus, the placenta allows the most appropriate environment and optimal fetal growth. The placenta of one sex sometimes has a greater ability over the other to respond to and protect against possible maternal insults. Here, we characterized sex differences in the placenta's morphological features and antioxidant status following dexamethasone (Dx) exposure. Pregnant rats were exposed to Dx or saline. The placenta was histologically and stereologically analyzed. The activity of the antioxidant enzymes, lipid peroxides (TBARS), superoxide anion and nitric oxide (NO) was measured. The decrease in placental zone volumes was more pronounced (p < 0.05) in female placentas. The volume density of PCNA-immunopositive nuclei was reduced (p < 0.05) in both sexes. The reduced (p < 0.05) antioxidant enzyme activities, enhanced TBARS and NO concentration indicate that Dx exposure triggered oxidative stress in the placenta of both fetal sexes, albeit stronger in the placenta of female fetuses. In conclusion, maternal Dx treatment reduced the size and volume of placental zones, altered placental histomorphology, decreased cell proliferation and triggered oxidative stress; however, the placentas of female fetuses exerted more significant responses to the treatment effects. The reduced placental size most probably reduced the transport of nutrients and oxygen, thus resulting in the reduced weight of fetuses, similar in both sexes. The lesser ability of the male placenta to detect and react to maternal exposure to environmental challenges may lead to long-standing health effects.",
publisher = "Basel: MDPI",
journal = "International Journal of Molecular Sciences",
title = "Maternal Dexamethasone Exposure Induces Sex-Specific Changes in Histomorphology and Redox Homeostasis of Rat Placenta",
number = "1",
volume = "24",
doi = "10.3390/ijms24010540",
pages = "540"
}

Trifunović, S., Šošić-Jurjević, B., Ristić, N., Nestorović, N., Filipović, B., Stevanović, I., Begović-Kuprešanin, V.,& Manojlović-Stojanoski, M.. (2023). Maternal Dexamethasone Exposure Induces Sex-Specific Changes in Histomorphology and Redox Homeostasis of Rat Placenta. in International Journal of Molecular Sciences
Basel: MDPI., 24(1), 540.
https://doi.org/10.3390/ijms24010540

Trifunović S, Šošić-Jurjević B, Ristić N, Nestorović N, Filipović B, Stevanović I, Begović-Kuprešanin V, Manojlović-Stojanoski M. Maternal Dexamethasone Exposure Induces Sex-Specific Changes in Histomorphology and Redox Homeostasis of Rat Placenta. in International Journal of Molecular Sciences. 2023;24(1):540.
doi:10.3390/ijms24010540 .

Trifunović, Svetlana, Šošić-Jurjević, Branka , Ristić, Nataša, Nestorović, Nataša, Filipović, Branko, Stevanović, Ivana, Begović-Kuprešanin, Vesna, Manojlović-Stojanoski, Milica, "Maternal Dexamethasone Exposure Induces Sex-Specific Changes in Histomorphology and Redox Homeostasis of Rat Placenta" in International Journal of Molecular Sciences, 24, no. 1 (2023):540,
https://doi.org/10.3390/ijms24010540 . .

TY  - CONF
AU  - Milošević, Katarina
AU  - Milošević, Ana
AU  - Živković, Anica
AU  - Stevanović, Ivana
AU  - Laketa, Danijela
AU  - Božić, Iva
AU  - Janjić, Marija
AU  - Bjelobaba, Ivana
AU  - Lavrnja, Irena
AU  - Savić, Danijela
PY  - 2023
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5875
AB  - Oxidative burst is a component of neuroinflammation whereby microglia-generated reactive oxygen species (ROS) either target pathogens or act as secondary messengers for microglial activation. In response to increased ROS during microglial activation, cytoprotective mechanisms are initiated primarily via Nrf2 activation and HO-1 expression. Agmatine is known to exert neuroprotective effect in vivo due to Nrf2 induction. While agmatine has been shown to activate the Nrf2/HO-1 signaling and protect macrophages from Lps-induced inflammation in vitro, its interaction with this pathway in activated microglia remains unexplored. Therefore, we sought to examine the potential of 100 μM agmatine as a pretreatment of Lps to activate Nrf2 in BV-2 microglia. In addition to cell viability, we analyzed the nuclear level of Nrf2 by Western blot and the expression of Hmox1 by PCR, as well as the protein level of HO-1. We also measured indicators of prooxidant and antioxidant activity: 4-HNE and total glutathione, respectively. Agmatine induces oxidative stress in non-stimulated microglia, as confirmed by the increase in the lipid peroxidation marker — 4-HNE, while cell viability stays preserved. Moreover, agmatine alone causes delayed Nrf2 nuclear overexpression and an increase in total glutathione content, eventually leading to an adaptive stress response. On the other hand, in Lps-stimulated microglia, agmatine prevents lipid peroxidation, readily upregulates the nuclear protein levels of Nrf2, which increases gene and protein expression of HO-1, and maintains delayed Nrf2 nuclear overexpression, resulting in increased total glutathione content associated with cytoprotection. Overall, we interpret agmatine-induced oxidative stress in non-activated microglia as triggering the adaptive response via Nrf2 and total glutathione, enabling them to cope with subsequent stressors, ie, Lps.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
T1  - Agmatine upregulates Nrf2/HO-1 pathway in Lps-stimulated microglia
SP  - 106
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5875
ER  - 

@conference{
author = "Milošević, Katarina and Milošević, Ana and Živković, Anica and Stevanović, Ivana and Laketa, Danijela and Božić, Iva and Janjić, Marija and Bjelobaba, Ivana and Lavrnja, Irena and Savić, Danijela",
year = "2023",
abstract = "Oxidative burst is a component of neuroinflammation whereby microglia-generated reactive oxygen species (ROS) either target pathogens or act as secondary messengers for microglial activation. In response to increased ROS during microglial activation, cytoprotective mechanisms are initiated primarily via Nrf2 activation and HO-1 expression. Agmatine is known to exert neuroprotective effect in vivo due to Nrf2 induction. While agmatine has been shown to activate the Nrf2/HO-1 signaling and protect macrophages from Lps-induced inflammation in vitro, its interaction with this pathway in activated microglia remains unexplored. Therefore, we sought to examine the potential of 100 μM agmatine as a pretreatment of Lps to activate Nrf2 in BV-2 microglia. In addition to cell viability, we analyzed the nuclear level of Nrf2 by Western blot and the expression of Hmox1 by PCR, as well as the protein level of HO-1. We also measured indicators of prooxidant and antioxidant activity: 4-HNE and total glutathione, respectively. Agmatine induces oxidative stress in non-stimulated microglia, as confirmed by the increase in the lipid peroxidation marker — 4-HNE, while cell viability stays preserved. Moreover, agmatine alone causes delayed Nrf2 nuclear overexpression and an increase in total glutathione content, eventually leading to an adaptive stress response. On the other hand, in Lps-stimulated microglia, agmatine prevents lipid peroxidation, readily upregulates the nuclear protein levels of Nrf2, which increases gene and protein expression of HO-1, and maintains delayed Nrf2 nuclear overexpression, resulting in increased total glutathione content associated with cytoprotection. Overall, we interpret agmatine-induced oxidative stress in non-activated microglia as triggering the adaptive response via Nrf2 and total glutathione, enabling them to cope with subsequent stressors, ie, Lps.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia",
title = "Agmatine upregulates Nrf2/HO-1 pathway in Lps-stimulated microglia",
pages = "106",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5875"
}

Milošević, K., Milošević, A., Živković, A., Stevanović, I., Laketa, D., Božić, I., Janjić, M., Bjelobaba, I., Lavrnja, I.,& Savić, D.. (2023). Agmatine upregulates Nrf2/HO-1 pathway in Lps-stimulated microglia. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 106.
https://hdl.handle.net/21.15107/rcub_ibiss_5875

Milošević K, Milošević A, Živković A, Stevanović I, Laketa D, Božić I, Janjić M, Bjelobaba I, Lavrnja I, Savić D. Agmatine upregulates Nrf2/HO-1 pathway in Lps-stimulated microglia. in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia. 2023;:106.
https://hdl.handle.net/21.15107/rcub_ibiss_5875 .

Milošević, Katarina, Milošević, Ana, Živković, Anica, Stevanović, Ivana, Laketa, Danijela, Božić, Iva, Janjić, Marija, Bjelobaba, Ivana, Lavrnja, Irena, Savić, Danijela, "Agmatine upregulates Nrf2/HO-1 pathway in Lps-stimulated microglia" in Book of abstracts: 8th Congress of Serbian neuroscience society with international participation; 2023 May 31 - Jun 2; Belgrade, Serbia (2023):106,
https://hdl.handle.net/21.15107/rcub_ibiss_5875 .

TY  - JOUR
AU  - Milošević, Katarina
AU  - Stevanović, Ivana
AU  - Božić, Iva
AU  - Milošević, Ana
AU  - Janjić, Marija
AU  - Laketa, Danijela
AU  - Bjelobaba, Ivana
AU  - Lavrnja, Irena
AU  - Savić, Danijela
PY  - 2022
UR  - https://www.mdpi.com/1422-0067/23/7/3561
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC8998340
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4948
AB  - Neuroinflammation and microglial activation, common components of most neurodegenerative diseases, can be imitated in vitro by challenging microglia cells with Lps. We here aimed to evaluate the effects of agmatine pretreatment on Lps-induced oxidative stress in a mouse microglial BV-2 cell line. Our findings show that agmatine suppresses nitrosative and oxidative burst in Lps-stimulated microglia by reducing iNOS and XO activity and decreasing O2- levels, arresting lipid peroxidation, increasing total glutathione content, and preserving GR and CAT activity. In accordance with these results, agmatine suppresses inflammatory NF-kB, and stimulates antioxidant Nrf2 pathway, resulting in decreased TNF, IL-1 beta, and IL-6 release, and reduced iNOS and COX-2 levels. Together with increased ARG1, CD206 and HO-1 levels, our results imply that, in inflammatory conditions, agmatine pushes microglia towards an anti-inflammatory phenotype. Interestingly, we also discovered that agmatine alone increases lipid peroxidation end product levels, induces Nrf2 activation, increases total glutathione content, and GPx activity. Thus, we hypothesize that some of the effects of agmatine, observed in activated microglia, may be mediated by induced oxidative stress and adaptive response, prior to Lps stimulation.
PB  - Basel: MDPI
T2  - International Journal of Molecular Sciences
T1  - Agmatine Mitigates Inflammation-Related Oxidative Stress in BV-2 Cells by Inducing a Pre-Adaptive Response.
IS  - 7
VL  - 23
DO  - 10.3390/ijms23073561
SP  - 3561
ER  - 

@article{
author = "Milošević, Katarina and Stevanović, Ivana and Božić, Iva and Milošević, Ana and Janjić, Marija and Laketa, Danijela and Bjelobaba, Ivana and Lavrnja, Irena and Savić, Danijela",
year = "2022",
abstract = "Neuroinflammation and microglial activation, common components of most neurodegenerative diseases, can be imitated in vitro by challenging microglia cells with Lps. We here aimed to evaluate the effects of agmatine pretreatment on Lps-induced oxidative stress in a mouse microglial BV-2 cell line. Our findings show that agmatine suppresses nitrosative and oxidative burst in Lps-stimulated microglia by reducing iNOS and XO activity and decreasing O2- levels, arresting lipid peroxidation, increasing total glutathione content, and preserving GR and CAT activity. In accordance with these results, agmatine suppresses inflammatory NF-kB, and stimulates antioxidant Nrf2 pathway, resulting in decreased TNF, IL-1 beta, and IL-6 release, and reduced iNOS and COX-2 levels. Together with increased ARG1, CD206 and HO-1 levels, our results imply that, in inflammatory conditions, agmatine pushes microglia towards an anti-inflammatory phenotype. Interestingly, we also discovered that agmatine alone increases lipid peroxidation end product levels, induces Nrf2 activation, increases total glutathione content, and GPx activity. Thus, we hypothesize that some of the effects of agmatine, observed in activated microglia, may be mediated by induced oxidative stress and adaptive response, prior to Lps stimulation.",
publisher = "Basel: MDPI",
journal = "International Journal of Molecular Sciences",
title = "Agmatine Mitigates Inflammation-Related Oxidative Stress in BV-2 Cells by Inducing a Pre-Adaptive Response.",
number = "7",
volume = "23",
doi = "10.3390/ijms23073561",
pages = "3561"
}

Milošević, K., Stevanović, I., Božić, I., Milošević, A., Janjić, M., Laketa, D., Bjelobaba, I., Lavrnja, I.,& Savić, D.. (2022). Agmatine Mitigates Inflammation-Related Oxidative Stress in BV-2 Cells by Inducing a Pre-Adaptive Response.. in International Journal of Molecular Sciences
Basel: MDPI., 23(7), 3561.
https://doi.org/10.3390/ijms23073561

Milošević K, Stevanović I, Božić I, Milošević A, Janjić M, Laketa D, Bjelobaba I, Lavrnja I, Savić D. Agmatine Mitigates Inflammation-Related Oxidative Stress in BV-2 Cells by Inducing a Pre-Adaptive Response.. in International Journal of Molecular Sciences. 2022;23(7):3561.
doi:10.3390/ijms23073561 .

Milošević, Katarina, Stevanović, Ivana, Božić, Iva, Milošević, Ana, Janjić, Marija, Laketa, Danijela, Bjelobaba, Ivana, Lavrnja, Irena, Savić, Danijela, "Agmatine Mitigates Inflammation-Related Oxidative Stress in BV-2 Cells by Inducing a Pre-Adaptive Response." in International Journal of Molecular Sciences, 23, no. 7 (2022):3561,
https://doi.org/10.3390/ijms23073561 . .

TY  - JOUR
AU  - Manojlović-Stojanoski, Milica
AU  - Lavrnja, Irena
AU  - Stevanović, Ivana
AU  - Trifunović, Svetlana
AU  - Ristić, Nataša
AU  - Nestorović, Nataša
AU  - Sévigny, Jean
AU  - Nedeljković, Nadežda
AU  - Laketa, Danijela
PY  - 2022
UR  - https://doi.org/10.1007/s10571-021-01081-8
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4187
AB  - Dexamethasone (DEX) is frequently used to treat women at risk of preterm delivery, but although indispensable for the completion of organ maturation in the fetus, antenatal DEX treatment may exert adverse sex-dimorphic neurodevelopmental effects. Literature findings implicated oxidative stress in adverse effects of DEX treatment. Purinergic signaling is involved in neurodevelopment and controlled by ectonucleotidases, among which in the brain the most abundant are ectonucleoside triphosphate diphosphohydrolase 1 (NTPDase1/CD39) and ecto-5ʹ-nucleotidase (e5ʹNT/CD73), which jointly dephosphorylate ATP to adenosine. They are also involved in cell adhesion and migration, processes integral to brain development. Upregulation of CD39 and CD73 after DEX treatment was reported in adult rat hippocampus. We investigated the effects of maternal DEX treatment on CD39 and CD73 expression and enzymatic activity in the rat fetal brain of both sexes, in the context of oxidative status of the brain tissue. Fetuses were obtained at embryonic day (ED) 21, from Wistar rat dams treated with 0.5 mg DEX/kg/day, at ED 16, 17, and 18, and brains were processed and used for further analysis. Sex-specific increase in CD39 and CD73 expression and in the corresponding enzyme activities was induced in the brain of antenatally DEX-treated fetuses, more prominently in males. The oxidative stress induction after antenatal DEX treatment was confirmed in both sexes, although showing a slight bias in males. Due to the involvement of purinergic system in crucial neurodevelopmental processes, future investigations are needed to determine the role of these observed changes in the adverse effects of antenatal DEX treatment.
PB  - Springer
T2  - Cellular and Molecular Neurobiology
T1  - Antenatal Dexamethasone Treatment Induces Sex-dependent Upregulation of NTPDase1/CD39 and Ecto-5ʹ-nucleotidase/CD73 in the Rat Fetal Brain
VL  - 42
DO  - 10.1007/s10571-021-01081-8
SP  - 1965
EP  - 1981
ER  - 

@article{
author = "Manojlović-Stojanoski, Milica and Lavrnja, Irena and Stevanović, Ivana and Trifunović, Svetlana and Ristić, Nataša and Nestorović, Nataša and Sévigny, Jean and Nedeljković, Nadežda and Laketa, Danijela",
year = "2022",
abstract = "Dexamethasone (DEX) is frequently used to treat women at risk of preterm delivery, but although indispensable for the completion of organ maturation in the fetus, antenatal DEX treatment may exert adverse sex-dimorphic neurodevelopmental effects. Literature findings implicated oxidative stress in adverse effects of DEX treatment. Purinergic signaling is involved in neurodevelopment and controlled by ectonucleotidases, among which in the brain the most abundant are ectonucleoside triphosphate diphosphohydrolase 1 (NTPDase1/CD39) and ecto-5ʹ-nucleotidase (e5ʹNT/CD73), which jointly dephosphorylate ATP to adenosine. They are also involved in cell adhesion and migration, processes integral to brain development. Upregulation of CD39 and CD73 after DEX treatment was reported in adult rat hippocampus. We investigated the effects of maternal DEX treatment on CD39 and CD73 expression and enzymatic activity in the rat fetal brain of both sexes, in the context of oxidative status of the brain tissue. Fetuses were obtained at embryonic day (ED) 21, from Wistar rat dams treated with 0.5 mg DEX/kg/day, at ED 16, 17, and 18, and brains were processed and used for further analysis. Sex-specific increase in CD39 and CD73 expression and in the corresponding enzyme activities was induced in the brain of antenatally DEX-treated fetuses, more prominently in males. The oxidative stress induction after antenatal DEX treatment was confirmed in both sexes, although showing a slight bias in males. Due to the involvement of purinergic system in crucial neurodevelopmental processes, future investigations are needed to determine the role of these observed changes in the adverse effects of antenatal DEX treatment.",
publisher = "Springer",
journal = "Cellular and Molecular Neurobiology",
title = "Antenatal Dexamethasone Treatment Induces Sex-dependent Upregulation of NTPDase1/CD39 and Ecto-5ʹ-nucleotidase/CD73 in the Rat Fetal Brain",
volume = "42",
doi = "10.1007/s10571-021-01081-8",
pages = "1965-1981"
}

Manojlović-Stojanoski, M., Lavrnja, I., Stevanović, I., Trifunović, S., Ristić, N., Nestorović, N., Sévigny, J., Nedeljković, N.,& Laketa, D.. (2022). Antenatal Dexamethasone Treatment Induces Sex-dependent Upregulation of NTPDase1/CD39 and Ecto-5ʹ-nucleotidase/CD73 in the Rat Fetal Brain. in Cellular and Molecular Neurobiology
Springer., 42, 1965-1981.
https://doi.org/10.1007/s10571-021-01081-8

Manojlović-Stojanoski M, Lavrnja I, Stevanović I, Trifunović S, Ristić N, Nestorović N, Sévigny J, Nedeljković N, Laketa D. Antenatal Dexamethasone Treatment Induces Sex-dependent Upregulation of NTPDase1/CD39 and Ecto-5ʹ-nucleotidase/CD73 in the Rat Fetal Brain. in Cellular and Molecular Neurobiology. 2022;42:1965-1981.
doi:10.1007/s10571-021-01081-8 .

Manojlović-Stojanoski, Milica, Lavrnja, Irena, Stevanović, Ivana, Trifunović, Svetlana, Ristić, Nataša, Nestorović, Nataša, Sévigny, Jean, Nedeljković, Nadežda, Laketa, Danijela, "Antenatal Dexamethasone Treatment Induces Sex-dependent Upregulation of NTPDase1/CD39 and Ecto-5ʹ-nucleotidase/CD73 in the Rat Fetal Brain" in Cellular and Molecular Neurobiology, 42 (2022):1965-1981,
https://doi.org/10.1007/s10571-021-01081-8 . .

TY  - CONF
AU  - Milošević, Katarina
AU  - Stevanović, Ivana
AU  - Božić, Iva
AU  - Milošević, Ana
AU  - Janjić, Marija
AU  - Laketa, Danijela
AU  - Bjelobaba, Ivana
AU  - Lavrnja, Irena
AU  - Savić, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5749
AB  - Prekomerna neuroinflamacija i mikroglijska aktivacija su uključene u patologiju mnogih neurodegenerativnih bolesti i mogu se simulirati u in vitro sistemu mikroglijskih ćelija primenom bakterijskog lipolisaharida (engl. Lipopolisaharide, LPS). Naša studija imala je za cilj da proceni efekte  pretretmana agmatinom na LPS-om izazvani oksidativni stres u BV-2 mišjoj mikroglijskoj ćelijskoj liniji. Pokazano je da u LPS-om stimulisanoj mikrogliji agmatin smanjuje enzimsku aktivnost iNOS i ksantin oksidaze (engl. Xanthine oxidase, XO), kao i nivo O2−, zaustavlja lipidnu peroksidaciju, povećava količinu ukupnog glutationa i omogućava da se delimično očuva aktivnost glutation reduktaze i katalaze, čime redukuje azotni i oksidativni stres. Agmatin utiče i na dva glavna signalna puta (NF-kB i Nrf2) uključena u inflamaciju, odnosno, antioksidativnu zaštitu, smanjujući tako nivo iNOS i COX-2, kao i oslobađanje TNF, IL-1β i IL-6. Istovremeno povećava se nivo ARG1, CD206 i HO-1, iz čega proizilazi da u uslovima inflamacije agmatin moduliše aktivaciju mikroglije u pravcu antiinflamacijskog fenotipa. Pokazali smo i da sam agmatin kod BV-2 ćelija dovodi do porasta nivoa krajnjih produkata lipidne peroksidacije, ali i ukupnog glutationa, aktivnosti glutation peroksidaze i aktivacije Nrf2 puta. Ovi rezultati podržavaju hipotezu da su agmatinom izazvani oksidativni stres i adaptivni odgovor, koji prethode stimulaciji LPS-om, odgovorni za efekte agmatina u aktiviranoj mikrogliji.
AB  - Прекомерена неуроинфламација и микроглијска активација су укључене у
патологију многих неуродегенеративних болести и могу се симулирати у in vitro
систему микроглијских ћелија применом бактеријског липолисахарида (енгл.
Lipopolisaharide, LPS). Наша студија имала је за циљ да процени ефекте
претретмана агматином на LPS-ом изазвани оксидативни стрес у BV-2 мишјој
микроглијској ћелијској линији. Показано је да у LPS-ом стимулисаној микроглији
агматин смањује ензимску активност iNOS и ксантин оксидазе (енгл. Xanthine
oxidase, XO), као и ниво O2−, зауставља липидну пероксидацију, повећава количину
укупног глутатиона и омогућава да се делимично очува активност глутатион
редуктазе и каталазе, чиме редукује азотни и оксидативни стрес. Агматин утиче и
на два главна сигнална пута (NF-kB и Nrf2) укључена у инфламацију, односно,
антиоксидативну заштиту, смањујући тако ниво iNOS и COX-2, као и ослобађање
TNF, IL-1β и IL-6. Истовремено повећава се ниво ARG1, CD206 и HO-1, из чега
произилази да у условима инфламације агматин модулише активацију микроглије
у правцу антиинфламацијског фенотипа. Показали смо и да сам агматин код BV-2
ћелија доводи до пораста нивоа крајњих продуката липидне пероксидације, али и
укупног глутатиона, активности глутатион пероксидазе и активације Nrf2 пута.
Ови резултати подржавају хипотезу да су агматином изазвани оксидативни стрес и
адаптивни одговор, који претходе стимулацији LPS-ом, одговорни за ефекте
агматина у активираној микроглији.
PB  - Belgrade: Serbian Biological Society
C3  - Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
T1  - Uticaj agmatina na oksidativni i inflamacijski odgovor mikroglijskih ćelija aktiviranih bakterijskim lipopolisaharidom
T1  - Утицај агматина на оксидативни и инфламацијски одговор микроглијских ћелија активираних бактеријским липополисахаридом
SP  - 290
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5749
ER  - 

@conference{
author = "Milošević, Katarina and Stevanović, Ivana and Božić, Iva and Milošević, Ana and Janjić, Marija and Laketa, Danijela and Bjelobaba, Ivana and Lavrnja, Irena and Savić, Danijela",
year = "2022",
abstract = "Prekomerna neuroinflamacija i mikroglijska aktivacija su uključene u patologiju mnogih neurodegenerativnih bolesti i mogu se simulirati u in vitro sistemu mikroglijskih ćelija primenom bakterijskog lipolisaharida (engl. Lipopolisaharide, LPS). Naša studija imala je za cilj da proceni efekte  pretretmana agmatinom na LPS-om izazvani oksidativni stres u BV-2 mišjoj mikroglijskoj ćelijskoj liniji. Pokazano je da u LPS-om stimulisanoj mikrogliji agmatin smanjuje enzimsku aktivnost iNOS i ksantin oksidaze (engl. Xanthine oxidase, XO), kao i nivo O2−, zaustavlja lipidnu peroksidaciju, povećava količinu ukupnog glutationa i omogućava da se delimično očuva aktivnost glutation reduktaze i katalaze, čime redukuje azotni i oksidativni stres. Agmatin utiče i na dva glavna signalna puta (NF-kB i Nrf2) uključena u inflamaciju, odnosno, antioksidativnu zaštitu, smanjujući tako nivo iNOS i COX-2, kao i oslobađanje TNF, IL-1β i IL-6. Istovremeno povećava se nivo ARG1, CD206 i HO-1, iz čega proizilazi da u uslovima inflamacije agmatin moduliše aktivaciju mikroglije u pravcu antiinflamacijskog fenotipa. Pokazali smo i da sam agmatin kod BV-2 ćelija dovodi do porasta nivoa krajnjih produkata lipidne peroksidacije, ali i ukupnog glutationa, aktivnosti glutation peroksidaze i aktivacije Nrf2 puta. Ovi rezultati podržavaju hipotezu da su agmatinom izazvani oksidativni stres i adaptivni odgovor, koji prethode stimulaciji LPS-om, odgovorni za efekte agmatina u aktiviranoj mikrogliji., Прекомерена неуроинфламација и микроглијска активација су укључене у
патологију многих неуродегенеративних болести и могу се симулирати у in vitro
систему микроглијских ћелија применом бактеријског липолисахарида (енгл.
Lipopolisaharide, LPS). Наша студија имала је за циљ да процени ефекте
претретмана агматином на LPS-ом изазвани оксидативни стрес у BV-2 мишјој
микроглијској ћелијској линији. Показано је да у LPS-ом стимулисаној микроглији
агматин смањује ензимску активност iNOS и ксантин оксидазе (енгл. Xanthine
oxidase, XO), као и ниво O2−, зауставља липидну пероксидацију, повећава количину
укупног глутатиона и омогућава да се делимично очува активност глутатион
редуктазе и каталазе, чиме редукује азотни и оксидативни стрес. Агматин утиче и
на два главна сигнална пута (NF-kB и Nrf2) укључена у инфламацију, односно,
антиоксидативну заштиту, смањујући тако ниво iNOS и COX-2, као и ослобађање
TNF, IL-1β и IL-6. Истовремено повећава се ниво ARG1, CD206 и HO-1, из чега
произилази да у условима инфламације агматин модулише активацију микроглије
у правцу антиинфламацијског фенотипа. Показали смо и да сам агматин код BV-2
ћелија доводи до пораста нивоа крајњих продуката липидне пероксидације, али и
укупног глутатиона, активности глутатион пероксидазе и активације Nrf2 пута.
Ови резултати подржавају хипотезу да су агматином изазвани оксидативни стрес и
адаптивни одговор, који претходе стимулацији LPS-ом, одговорни за ефекте
агматина у активираној микроглији.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia",
title = "Uticaj agmatina na oksidativni i inflamacijski odgovor mikroglijskih ćelija aktiviranih bakterijskim lipopolisaharidom, Утицај агматина на оксидативни и инфламацијски одговор микроглијских ћелија активираних бактеријским липополисахаридом",
pages = "290",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5749"
}

Milošević, K., Stevanović, I., Božić, I., Milošević, A., Janjić, M., Laketa, D., Bjelobaba, I., Lavrnja, I.,& Savić, D.. (2022). Uticaj agmatina na oksidativni i inflamacijski odgovor mikroglijskih ćelija aktiviranih bakterijskim lipopolisaharidom. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
Belgrade: Serbian Biological Society., 290.
https://hdl.handle.net/21.15107/rcub_ibiss_5749

Milošević K, Stevanović I, Božić I, Milošević A, Janjić M, Laketa D, Bjelobaba I, Lavrnja I, Savić D. Uticaj agmatina na oksidativni i inflamacijski odgovor mikroglijskih ćelija aktiviranih bakterijskim lipopolisaharidom. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia. 2022;:290.
https://hdl.handle.net/21.15107/rcub_ibiss_5749 .

Milošević, Katarina, Stevanović, Ivana, Božić, Iva, Milošević, Ana, Janjić, Marija, Laketa, Danijela, Bjelobaba, Ivana, Lavrnja, Irena, Savić, Danijela, "Uticaj agmatina na oksidativni i inflamacijski odgovor mikroglijskih ćelija aktiviranih bakterijskim lipopolisaharidom" in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia (2022):290,
https://hdl.handle.net/21.15107/rcub_ibiss_5749 .

TY  - CONF
AU  - Manojlović-Stojanoski, Milica
AU  - Lavrnja, Irena
AU  - Stevanović, Ivana
AU  - Trifunović, Svetlana
AU  - Ristić, Nataša
AU  - Nestorović, Nataša
AU  - Nedeljković, Nadežda
AU  - Laketa, Danijela
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5750
AB  - Kod prevremeno rođene dece, nedovoljna izloženost endogenim glukokortikoidima vodi često do fatalnih komplikacija, koje mogu biti sprečene antenatalnim tretmanom sintetskim glukokortikoidima, najčešće deksametazonom (DEKS). Prema važećim preporukama, trudnice u riziku od prevremenog porođaja između 24-te i 34-te nedelje trudnoće treba da prime jedan tretman deksametazonom. I pored rizika od neželjenih neurorazvojnih efekata, često se primenjuje ponavljani tretman. Purinski signalni sistem ima važnu ulogu u razviću mozga, a ključnu ulogu imaju najzastupljenije ektonukleotidaze NTPDaza1/CD39 i ekto-5ʹ-nukleotidaza/CD73 koje zajednički regulišu nivo ATP, ADP i adenozina u vanćelijskoj tečnosti. Mi smo primenili antenatalni ponavljani tretman deksametazonom (APTD) 15, 16 i 17 dana gestacije (DG) kod trudnih ženki Wistar pacova. Fetusi su dobijeni 21. DG, a nakon dekapitacije izolovan je mozak koji je po uklanjanju cerebellum-a korišćen za dobijanje grube membranske frakcije, iRNK ili pripremljen za imunohistohemijsku analizu. Naši rezultati pokazuju da APTD izaziva porast genske i proteinske ekspresije, kao i enzimske aktivnosti NTPDaze1/CD39 i ekto-5ʹ-nukleotidaze/CD73 u mozgu fetusa kod pacova, koji je izraženiji kod muškog pola. Uočene promene ukazuju da APTD verovatno izaziva smanjenje ATP- i ADP-zavisne, a porast adenozinske signalizacije, izraženije u mozgu muških fetusa što bi moglo da doprinosi neželjenim neurorazvojnim efektima APTD, posebno kod muškog pola.
PB  - Belgrade: Serbian Biological Society
C3  - Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
T1  - Ponavljani antenatalni tretman deksametazonom izaziva polno-zavisni porast ekspresije glavnih ektonukleotidaza u mozgu fetusa kod pacova
T1  - Понављани антенатални третман дексаметазоном изазива полно-зависни пораст експресије главних ектонуклеотидаза у мозгу фетуса код пацова
SP  - 351
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5750
ER  - 

@conference{
author = "Manojlović-Stojanoski, Milica and Lavrnja, Irena and Stevanović, Ivana and Trifunović, Svetlana and Ristić, Nataša and Nestorović, Nataša and Nedeljković, Nadežda and Laketa, Danijela",
year = "2022",
abstract = "Kod prevremeno rođene dece, nedovoljna izloženost endogenim glukokortikoidima vodi često do fatalnih komplikacija, koje mogu biti sprečene antenatalnim tretmanom sintetskim glukokortikoidima, najčešće deksametazonom (DEKS). Prema važećim preporukama, trudnice u riziku od prevremenog porođaja između 24-te i 34-te nedelje trudnoće treba da prime jedan tretman deksametazonom. I pored rizika od neželjenih neurorazvojnih efekata, često se primenjuje ponavljani tretman. Purinski signalni sistem ima važnu ulogu u razviću mozga, a ključnu ulogu imaju najzastupljenije ektonukleotidaze NTPDaza1/CD39 i ekto-5ʹ-nukleotidaza/CD73 koje zajednički regulišu nivo ATP, ADP i adenozina u vanćelijskoj tečnosti. Mi smo primenili antenatalni ponavljani tretman deksametazonom (APTD) 15, 16 i 17 dana gestacije (DG) kod trudnih ženki Wistar pacova. Fetusi su dobijeni 21. DG, a nakon dekapitacije izolovan je mozak koji je po uklanjanju cerebellum-a korišćen za dobijanje grube membranske frakcije, iRNK ili pripremljen za imunohistohemijsku analizu. Naši rezultati pokazuju da APTD izaziva porast genske i proteinske ekspresije, kao i enzimske aktivnosti NTPDaze1/CD39 i ekto-5ʹ-nukleotidaze/CD73 u mozgu fetusa kod pacova, koji je izraženiji kod muškog pola. Uočene promene ukazuju da APTD verovatno izaziva smanjenje ATP- i ADP-zavisne, a porast adenozinske signalizacije, izraženije u mozgu muških fetusa što bi moglo da doprinosi neželjenim neurorazvojnim efektima APTD, posebno kod muškog pola.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia",
title = "Ponavljani antenatalni tretman deksametazonom izaziva polno-zavisni porast ekspresije glavnih ektonukleotidaza u mozgu fetusa kod pacova, Понављани антенатални третман дексаметазоном изазива полно-зависни пораст експресије главних ектонуклеотидаза у мозгу фетуса код пацова",
pages = "351",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5750"
}

Manojlović-Stojanoski, M., Lavrnja, I., Stevanović, I., Trifunović, S., Ristić, N., Nestorović, N., Nedeljković, N.,& Laketa, D.. (2022). Ponavljani antenatalni tretman deksametazonom izaziva polno-zavisni porast ekspresije glavnih ektonukleotidaza u mozgu fetusa kod pacova. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia
Belgrade: Serbian Biological Society., 351.
https://hdl.handle.net/21.15107/rcub_ibiss_5750

Manojlović-Stojanoski M, Lavrnja I, Stevanović I, Trifunović S, Ristić N, Nestorović N, Nedeljković N, Laketa D. Ponavljani antenatalni tretman deksametazonom izaziva polno-zavisni porast ekspresije glavnih ektonukleotidaza u mozgu fetusa kod pacova. in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia. 2022;:351.
https://hdl.handle.net/21.15107/rcub_ibiss_5750 .

Manojlović-Stojanoski, Milica, Lavrnja, Irena, Stevanović, Ivana, Trifunović, Svetlana, Ristić, Nataša, Nestorović, Nataša, Nedeljković, Nadežda, Laketa, Danijela, "Ponavljani antenatalni tretman deksametazonom izaziva polno-zavisni porast ekspresije glavnih ektonukleotidaza u mozgu fetusa kod pacova" in Knjiga sažetaka: Treći Kongres biologa Srbije: Osnovna i primenjena istraživanja: Metodika nastave; 2022 Sep 21-25; Zlatibor, Serbia (2022):351,
https://hdl.handle.net/21.15107/rcub_ibiss_5750 .

TY  - CONF
AU  - Milošević, Katarina
AU  - Stevanović, Ivana
AU  - Božić, Iva
AU  - Milošević, Ana
AU  - Jakovljević, Marija
AU  - Janjić, Marija
AU  - Bjelobaba, Ivana
AU  - Laketa, Danijela
AU  - Lavrnja, Irena
AU  - Savić, Danijela
PY  - 2021
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/6003
AB  - Mitochondria play a key role in energy metabolism and regulate some of the principal cellular processes such as the production of ATP and reactive oxygen species, as well as a regulation of apoptotic cell death. Mitochondrial dysfunction and oxidative stress are common threads in most neurodegenerative disorders, which are also accompanied by chronic microglial activation. Agmatine, neuromodulatory polyamine, was shown to exhibit neuroprotective effects in oxidative stress conditions. Therefore, the goal of this study was to determine the ability of agmatine to preserve mitochondrial function and prevent apoptosis during neuroinflammation.
The effects of 100 µM agmatine on cellular energy status and cell death were examined in LPS-stimulated BV2 microglial cell line. To detect changes in mitochondrial membrane potential, TMRE fluorescent assay was performed, while the changes in intracellular ATP concentration were determined by bioluminescent assay, 6h, and 24h after LPS stimulation. The expression of apoptosis regulators Bax and Bcl2 was assessed by Western blot analysis and the Bax/Bcl2 ratio was determined.
Agmatine increases mitochondrial membrane potential, indicating its protective role during mitochondrial insult caused by LPS stimulation. LPS and agmatine administrated separately, increase intracellular ATP levels, however, agmatine treatment followed by LPS stimulation enhances ATP production even further, at both time points. Moreover, agmatine shows an antiapoptotic effect by reduction of Bax/Bcl2 ratio in comparison to LPS stimulation.
We conclude that the results of this study indicate the capacity of agmatine to protect mitochondrial function and suppress apoptosis, which may be beneficial in neurodegenerative disorders and
neuroinflammation.
PB  - Federation of European Neuroscience Societies
C3  - Book of Abstracts: Virtual FENS Regional Meeting 2021; 2021 Aug 25-27; Krakow, Poland
T1  - Agmatine protects mitochondria in LPS-stimulated microglia
SP  - 285
EP  - 286
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_6003
ER  - 

@conference{
author = "Milošević, Katarina and Stevanović, Ivana and Božić, Iva and Milošević, Ana and Jakovljević, Marija and Janjić, Marija and Bjelobaba, Ivana and Laketa, Danijela and Lavrnja, Irena and Savić, Danijela",
year = "2021",
abstract = "Mitochondria play a key role in energy metabolism and regulate some of the principal cellular processes such as the production of ATP and reactive oxygen species, as well as a regulation of apoptotic cell death. Mitochondrial dysfunction and oxidative stress are common threads in most neurodegenerative disorders, which are also accompanied by chronic microglial activation. Agmatine, neuromodulatory polyamine, was shown to exhibit neuroprotective effects in oxidative stress conditions. Therefore, the goal of this study was to determine the ability of agmatine to preserve mitochondrial function and prevent apoptosis during neuroinflammation.
The effects of 100 µM agmatine on cellular energy status and cell death were examined in LPS-stimulated BV2 microglial cell line. To detect changes in mitochondrial membrane potential, TMRE fluorescent assay was performed, while the changes in intracellular ATP concentration were determined by bioluminescent assay, 6h, and 24h after LPS stimulation. The expression of apoptosis regulators Bax and Bcl2 was assessed by Western blot analysis and the Bax/Bcl2 ratio was determined.
Agmatine increases mitochondrial membrane potential, indicating its protective role during mitochondrial insult caused by LPS stimulation. LPS and agmatine administrated separately, increase intracellular ATP levels, however, agmatine treatment followed by LPS stimulation enhances ATP production even further, at both time points. Moreover, agmatine shows an antiapoptotic effect by reduction of Bax/Bcl2 ratio in comparison to LPS stimulation.
We conclude that the results of this study indicate the capacity of agmatine to protect mitochondrial function and suppress apoptosis, which may be beneficial in neurodegenerative disorders and
neuroinflammation.",
publisher = "Federation of European Neuroscience Societies",
journal = "Book of Abstracts: Virtual FENS Regional Meeting 2021; 2021 Aug 25-27; Krakow, Poland",
title = "Agmatine protects mitochondria in LPS-stimulated microglia",
pages = "285-286",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_6003"
}

Milošević, K., Stevanović, I., Božić, I., Milošević, A., Jakovljević, M., Janjić, M., Bjelobaba, I., Laketa, D., Lavrnja, I.,& Savić, D.. (2021). Agmatine protects mitochondria in LPS-stimulated microglia. in Book of Abstracts: Virtual FENS Regional Meeting 2021; 2021 Aug 25-27; Krakow, Poland
Federation of European Neuroscience Societies., 285-286.
https://hdl.handle.net/21.15107/rcub_ibiss_6003

Milošević K, Stevanović I, Božić I, Milošević A, Jakovljević M, Janjić M, Bjelobaba I, Laketa D, Lavrnja I, Savić D. Agmatine protects mitochondria in LPS-stimulated microglia. in Book of Abstracts: Virtual FENS Regional Meeting 2021; 2021 Aug 25-27; Krakow, Poland. 2021;:285-286.
https://hdl.handle.net/21.15107/rcub_ibiss_6003 .

Milošević, Katarina, Stevanović, Ivana, Božić, Iva, Milošević, Ana, Jakovljević, Marija, Janjić, Marija, Bjelobaba, Ivana, Laketa, Danijela, Lavrnja, Irena, Savić, Danijela, "Agmatine protects mitochondria in LPS-stimulated microglia" in Book of Abstracts: Virtual FENS Regional Meeting 2021; 2021 Aug 25-27; Krakow, Poland (2021):285-286,
https://hdl.handle.net/21.15107/rcub_ibiss_6003 .

TY  - JOUR
AU  - Dejanović, Bratislav
AU  - Begović-Kuprešanin, Vesna
AU  - Stevanović, Ivana
AU  - Lavrnja, Irena
AU  - Šošić-Jurjević, Branka 
AU  - Ninković, Milica
AU  - Trifunović, Svetlana
PY  - 2021
UR  - http://www.doiserbia.nb.rs/Article.aspx?ID=0354-46642100028D
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4651
UR  - https://www.serbiosoc.org.rs/arch/index.php/abs/article/view/6557
AB  - The use of the antidepressant drug chlorpromazine (CPZ) is linked to the occurrence of oxidative stress in some brain structures. Thus, overcoming the side effects of CPZ is of great importance. Because agmatine (AGM) can act as a free radical scavenger, it is an interesting compound as an adjunct to CPZ therapy. The aim of our study was to investigate the enzymatic parameters of oxidative stress in the hippocampus and striatum of rats after CPZ treatment, and the potential protective effects of AGM. Rats were injected as follows with (i) 1 mL/kg b.w. saline; (ii) a single intraperitoneal (i.p.) dose of CPZ (38.7 mg/kg); (iii) CPZ (38.7 mg/kg) and AGM (75 mg/kg); (iv) AGM (75 mg/kg). CPZ induced an increase in superoxide anion radical (O2 catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR), were lowered in both the hippocampus striatum. Cotreatment with CPZ and AGM protected the examined brain structures by reversing the antioxidant enzyme control values. Following CPZ treatment, the effects were more pronounced for SOD and GPx in the hippocampus, the striatum. The full effect of restored superoxide production was achieved in the striatum, which points to the role of CAT. The obtained results suggest that CPZ in combination with AGM may be considered as a new treatment strategy.
PB  - Belgrade: Serbian Biological Society
T2  - Archives of Biological Sciences
T1  - Agmatine reduces chlorpromazine prooxidant effects in rat hippocampus and striatum
IS  - 3
VL  - 73
DO  - 10.2298/abs210429028d
SP  - 353
EP  - 359
ER  - 

@article{
author = "Dejanović, Bratislav and Begović-Kuprešanin, Vesna and Stevanović, Ivana and Lavrnja, Irena and Šošić-Jurjević, Branka  and Ninković, Milica and Trifunović, Svetlana",
year = "2021",
abstract = "The use of the antidepressant drug chlorpromazine (CPZ) is linked to the occurrence of oxidative stress in some brain structures. Thus, overcoming the side effects of CPZ is of great importance. Because agmatine (AGM) can act as a free radical scavenger, it is an interesting compound as an adjunct to CPZ therapy. The aim of our study was to investigate the enzymatic parameters of oxidative stress in the hippocampus and striatum of rats after CPZ treatment, and the potential protective effects of AGM. Rats were injected as follows with (i) 1 mL/kg b.w. saline; (ii) a single intraperitoneal (i.p.) dose of CPZ (38.7 mg/kg); (iii) CPZ (38.7 mg/kg) and AGM (75 mg/kg); (iv) AGM (75 mg/kg). CPZ induced an increase in superoxide anion radical (O2 catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR), were lowered in both the hippocampus striatum. Cotreatment with CPZ and AGM protected the examined brain structures by reversing the antioxidant enzyme control values. Following CPZ treatment, the effects were more pronounced for SOD and GPx in the hippocampus, the striatum. The full effect of restored superoxide production was achieved in the striatum, which points to the role of CAT. The obtained results suggest that CPZ in combination with AGM may be considered as a new treatment strategy.",
publisher = "Belgrade: Serbian Biological Society",
journal = "Archives of Biological Sciences",
title = "Agmatine reduces chlorpromazine prooxidant effects in rat hippocampus and striatum",
number = "3",
volume = "73",
doi = "10.2298/abs210429028d",
pages = "353-359"
}

Dejanović, B., Begović-Kuprešanin, V., Stevanović, I., Lavrnja, I., Šošić-Jurjević, B., Ninković, M.,& Trifunović, S.. (2021). Agmatine reduces chlorpromazine prooxidant effects in rat hippocampus and striatum. in Archives of Biological Sciences
Belgrade: Serbian Biological Society., 73(3), 353-359.
https://doi.org/10.2298/abs210429028d

Dejanović B, Begović-Kuprešanin V, Stevanović I, Lavrnja I, Šošić-Jurjević B, Ninković M, Trifunović S. Agmatine reduces chlorpromazine prooxidant effects in rat hippocampus and striatum. in Archives of Biological Sciences. 2021;73(3):353-359.
doi:10.2298/abs210429028d .

Dejanović, Bratislav, Begović-Kuprešanin, Vesna, Stevanović, Ivana, Lavrnja, Irena, Šošić-Jurjević, Branka , Ninković, Milica, Trifunović, Svetlana, "Agmatine reduces chlorpromazine prooxidant effects in rat hippocampus and striatum" in Archives of Biological Sciences, 73, no. 3 (2021):353-359,
https://doi.org/10.2298/abs210429028d . .

TY  - JOUR
AU  - Trifunović, Svetlana
AU  - Stevanović, Ivana
AU  - Milošević, Ana
AU  - Ristić, Nataša
AU  - Janjić, Marija
AU  - Bjelobaba, Ivana
AU  - Savić, Danijela
AU  - Božić, Iva
AU  - Jakovljević, Marija
AU  - Milošević, Katarina
AU  - Laketa, Danijela
AU  - Lavrnja, Irena
PY  - 2021
UR  - https://www.frontiersin.org/articles/10.3389/fnins.2021.649485/full
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4436
AB  - Multiple sclerosis (MS) is an inflammatory, demyelinating disease with an unknown origin. Previous studies showed the involvement of the hypothalamic-pituitary-adrenal (HPA) axis to susceptibility to autoimmune diseases, including MS, and its best-characterized animal model, experimental autoimmune encephalomyelitis (EAE). During MS/EAE, innate immune cells are activated and release cytokines and other inflammatory mediators, leading to a vicious cycle of inflammation. In response to inflammation, the activated HPA axis modulates immune responses via glucocorticoid activity. Because the mechanisms involving oxidative stress to the HPA axis are relatively unrevealed, in this study, we investigate the inflammatory and oxidative stress status of HPA axis during EAE. Our results reveal an upregulation of Pomc gene expression, followed by POMC and ACTH protein increase at the peak of the EAE in the pituitary. Also, prostaglandins are well-known contributors of HPA axis activation, which increases during EAE at the periphery. The upregulated Tnf expression in the pituitary during the peak of EAE occurred. This leads to the activation of oxidative pathways, followed by upregulation of inducible NO synthase expression. The reactive oxidant/nitrosative species (ROS/RNS), such as superoxide anion and NO, increase their levels at the onset and peak of the disease in the pituitary and adrenal glands, returning to control levels at the end of EAE. The corticotrophs in the pituitary increased in number and volume at the peak of EAE that coincides with high lipid peroxidation levels. The expression of MC2R in the adrenal glands increases at the peak of EAE, where strong induction of superoxide anion and malondialdehyde (MDA), reduced total glutathione (GSH) content, and catalase activity occurred at the peak and end of EAE compared with controls. The results obtained from this study may help in understanding the mechanisms and possible pharmacological modulation in MS and demonstrate an effect of oxidative stress exposure in the HPA activation during the course of EAE.
PB  - Lausanne: Frontiers Media SA
T2  - Frontiers in Neuroscience
T1  - The Function of the Hypothalamic-Pituitary-Adrenal Axis During Experimental Autoimmune Encephalomyelitis: Involvement of Oxidative Stress Mediators.
VL  - 15
DO  - 10.3389/fnins.2021.649485
SP  - 649485
ER  - 

@article{
author = "Trifunović, Svetlana and Stevanović, Ivana and Milošević, Ana and Ristić, Nataša and Janjić, Marija and Bjelobaba, Ivana and Savić, Danijela and Božić, Iva and Jakovljević, Marija and Milošević, Katarina and Laketa, Danijela and Lavrnja, Irena",
year = "2021",
abstract = "Multiple sclerosis (MS) is an inflammatory, demyelinating disease with an unknown origin. Previous studies showed the involvement of the hypothalamic-pituitary-adrenal (HPA) axis to susceptibility to autoimmune diseases, including MS, and its best-characterized animal model, experimental autoimmune encephalomyelitis (EAE). During MS/EAE, innate immune cells are activated and release cytokines and other inflammatory mediators, leading to a vicious cycle of inflammation. In response to inflammation, the activated HPA axis modulates immune responses via glucocorticoid activity. Because the mechanisms involving oxidative stress to the HPA axis are relatively unrevealed, in this study, we investigate the inflammatory and oxidative stress status of HPA axis during EAE. Our results reveal an upregulation of Pomc gene expression, followed by POMC and ACTH protein increase at the peak of the EAE in the pituitary. Also, prostaglandins are well-known contributors of HPA axis activation, which increases during EAE at the periphery. The upregulated Tnf expression in the pituitary during the peak of EAE occurred. This leads to the activation of oxidative pathways, followed by upregulation of inducible NO synthase expression. The reactive oxidant/nitrosative species (ROS/RNS), such as superoxide anion and NO, increase their levels at the onset and peak of the disease in the pituitary and adrenal glands, returning to control levels at the end of EAE. The corticotrophs in the pituitary increased in number and volume at the peak of EAE that coincides with high lipid peroxidation levels. The expression of MC2R in the adrenal glands increases at the peak of EAE, where strong induction of superoxide anion and malondialdehyde (MDA), reduced total glutathione (GSH) content, and catalase activity occurred at the peak and end of EAE compared with controls. The results obtained from this study may help in understanding the mechanisms and possible pharmacological modulation in MS and demonstrate an effect of oxidative stress exposure in the HPA activation during the course of EAE.",
publisher = "Lausanne: Frontiers Media SA",
journal = "Frontiers in Neuroscience",
title = "The Function of the Hypothalamic-Pituitary-Adrenal Axis During Experimental Autoimmune Encephalomyelitis: Involvement of Oxidative Stress Mediators.",
volume = "15",
doi = "10.3389/fnins.2021.649485",
pages = "649485"
}

Trifunović, S., Stevanović, I., Milošević, A., Ristić, N., Janjić, M., Bjelobaba, I., Savić, D., Božić, I., Jakovljević, M., Milošević, K., Laketa, D.,& Lavrnja, I.. (2021). The Function of the Hypothalamic-Pituitary-Adrenal Axis During Experimental Autoimmune Encephalomyelitis: Involvement of Oxidative Stress Mediators.. in Frontiers in Neuroscience
Lausanne: Frontiers Media SA., 15, 649485.
https://doi.org/10.3389/fnins.2021.649485

Trifunović S, Stevanović I, Milošević A, Ristić N, Janjić M, Bjelobaba I, Savić D, Božić I, Jakovljević M, Milošević K, Laketa D, Lavrnja I. The Function of the Hypothalamic-Pituitary-Adrenal Axis During Experimental Autoimmune Encephalomyelitis: Involvement of Oxidative Stress Mediators.. in Frontiers in Neuroscience. 2021;15:649485.
doi:10.3389/fnins.2021.649485 .

Trifunović, Svetlana, Stevanović, Ivana, Milošević, Ana, Ristić, Nataša, Janjić, Marija, Bjelobaba, Ivana, Savić, Danijela, Božić, Iva, Jakovljević, Marija, Milošević, Katarina, Laketa, Danijela, Lavrnja, Irena, "The Function of the Hypothalamic-Pituitary-Adrenal Axis During Experimental Autoimmune Encephalomyelitis: Involvement of Oxidative Stress Mediators." in Frontiers in Neuroscience, 15 (2021):649485,
https://doi.org/10.3389/fnins.2021.649485 . .

TY  - JOUR
AU  - Dragić, Milorad
AU  - Zeljković, Milica
AU  - Stevanović, Ivana
AU  - Ilić, Tihomir
AU  - Ilić, Nela
AU  - Nedeljković, Nadezda
AU  - Ninković, Milica
PY  - 2020
UR  - http://www.ncbi.nlm.nih.gov/pubmed/32599126
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3768
AB  - Multiple sclerosis (MS) is a chronic neurodegenerative disease caused by inflammatory processes in the central nervous system (CNS). Decades of research led to discovery of several disease-modifying therapeutics strategies with moderate success. Experimental autoimmune encephalomyelitis (EAE) is currently the most commonly used experimental model for MS and for studying various therapeutic approaches. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neurostimulation technique with multiple beneficial effects on healthy as well as CNS with pathology. However, the molecular and cellular mechanisms of rTMS on acute EAE are scarce. Our study demonstrated beneficial effects of theta-burst stimulation (TBS), an experimental paradigm of rTMS, on disease course of acute EAE. TBS treatment attenuated reactive gliosis, restored myelin sheet and down-regulated expression of vimentin in EAE rats. These effects were reflected through reduced clinical parameters, shorter duration of illness and days spent in paralysis. Based on our research, rTMS deserves further considerations for its neuroprotective effect on EAE, and is an excellent candidate for further research and points that it could be used for more than for simple symptomatic therapy.
PB  - Elsevier BV
T2  - Brain Research Bulletin
T1  - Theta burst stimulation ameliorates symptoms of experimental autoimmune encephalomyelitis and attenuates reactive gliosis.
VL  - 162
DO  - 10.1016/j.brainresbull.2020.06.013
SP  - 208
EP  - 217
ER  - 

@article{
author = "Dragić, Milorad and Zeljković, Milica and Stevanović, Ivana and Ilić, Tihomir and Ilić, Nela and Nedeljković, Nadezda and Ninković, Milica",
year = "2020",
abstract = "Multiple sclerosis (MS) is a chronic neurodegenerative disease caused by inflammatory processes in the central nervous system (CNS). Decades of research led to discovery of several disease-modifying therapeutics strategies with moderate success. Experimental autoimmune encephalomyelitis (EAE) is currently the most commonly used experimental model for MS and for studying various therapeutic approaches. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neurostimulation technique with multiple beneficial effects on healthy as well as CNS with pathology. However, the molecular and cellular mechanisms of rTMS on acute EAE are scarce. Our study demonstrated beneficial effects of theta-burst stimulation (TBS), an experimental paradigm of rTMS, on disease course of acute EAE. TBS treatment attenuated reactive gliosis, restored myelin sheet and down-regulated expression of vimentin in EAE rats. These effects were reflected through reduced clinical parameters, shorter duration of illness and days spent in paralysis. Based on our research, rTMS deserves further considerations for its neuroprotective effect on EAE, and is an excellent candidate for further research and points that it could be used for more than for simple symptomatic therapy.",
publisher = "Elsevier BV",
journal = "Brain Research Bulletin",
title = "Theta burst stimulation ameliorates symptoms of experimental autoimmune encephalomyelitis and attenuates reactive gliosis.",
volume = "162",
doi = "10.1016/j.brainresbull.2020.06.013",
pages = "208-217"
}

Dragić, M., Zeljković, M., Stevanović, I., Ilić, T., Ilić, N., Nedeljković, N.,& Ninković, M.. (2020). Theta burst stimulation ameliorates symptoms of experimental autoimmune encephalomyelitis and attenuates reactive gliosis.. in Brain Research Bulletin
Elsevier BV., 162, 208-217.
https://doi.org/10.1016/j.brainresbull.2020.06.013

Dragić M, Zeljković M, Stevanović I, Ilić T, Ilić N, Nedeljković N, Ninković M. Theta burst stimulation ameliorates symptoms of experimental autoimmune encephalomyelitis and attenuates reactive gliosis.. in Brain Research Bulletin. 2020;162:208-217.
doi:10.1016/j.brainresbull.2020.06.013 .

Dragić, Milorad, Zeljković, Milica, Stevanović, Ivana, Ilić, Tihomir, Ilić, Nela, Nedeljković, Nadezda, Ninković, Milica, "Theta burst stimulation ameliorates symptoms of experimental autoimmune encephalomyelitis and attenuates reactive gliosis." in Brain Research Bulletin, 162 (2020):208-217,
https://doi.org/10.1016/j.brainresbull.2020.06.013 . .

TY  - JOUR
AU  - Stevanović, Ivana
AU  - Mančić, Bojana
AU  - Ilić, Tihomir
AU  - Milosavljević, Petar
AU  - Lavrnja, Irena
AU  - Stojanović, Ivana
AU  - Ninković, Milica
PY  - 2019
UR  - https://www.termedia.pl/doi/10.5114/fn.2019.86294
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3480
AB  - Repetitive transcranial magnetic stimulation (rTMS) induces changes in expression of proteins engaged in the activity of excitatory and inhibitory systems, restores these functions and suppresses the progression of disability in experimental autoimmune encephalitis (EAE). The structural type of TMS, the arrangement as theta burst stimulation (TBS) has been applied as intermittent TBS (iTBS) and continuous TBS (cTBS) protocols to female adult DA rats. The animals were randomly divided into experimental groups: control group (C), group treated with complete Freund's adjuvant (CFA), experimental autoimmune encephalomyelitis (EAE) group, group treated with iTBS post EAE immunization (EAE + iTBS), group treated with cTBS post EAE immunization (EAE + cTBS), group of healthy animals treated with iTBS or cTBS. Therapeutic protocols of iTBS or cTBS in all EAE groups of animals were performed starting from 14 days post immunization (dpi), for 10 days with time point decapitation at 24 dpi. After decapitation, spinal cords were analysed for BDNF and Ki67 expression. The results revealed reduced BDNF expression in the rat's spinal cord of EAE animals in the stage of remission, which was associated with increased Ki67 and GFAP expressions. Decreased Iba 1 and BDNF expression, contrary to increased Iba 1 and Ki67 expression, suggests clustered microglia in the resolution phase of EAE. Enhanced GABA expression in spinal cord sections indicates higher GABA metabolic turnover, and also GAD activity in astrocytes, or prominent activity of GABAergic neurons. Both TBS protocols induced advance BDNF expression; amongst iTBS application provoked elevating of BDNF and stabilizing of GFAP and Ki67 expressions.
T2  - Folia Neuropathologica
T1  - Theta burst stimulation influence the expression of BDNF in the spinal cord on the experimental autoimmune encephalomyelitis.
IS  - 2
VL  - 57
DO  - 10.5114/fn.2019.86294
SP  - 129
EP  - 145
ER  - 

@article{
author = "Stevanović, Ivana and Mančić, Bojana and Ilić, Tihomir and Milosavljević, Petar and Lavrnja, Irena and Stojanović, Ivana and Ninković, Milica",
year = "2019",
abstract = "Repetitive transcranial magnetic stimulation (rTMS) induces changes in expression of proteins engaged in the activity of excitatory and inhibitory systems, restores these functions and suppresses the progression of disability in experimental autoimmune encephalitis (EAE). The structural type of TMS, the arrangement as theta burst stimulation (TBS) has been applied as intermittent TBS (iTBS) and continuous TBS (cTBS) protocols to female adult DA rats. The animals were randomly divided into experimental groups: control group (C), group treated with complete Freund's adjuvant (CFA), experimental autoimmune encephalomyelitis (EAE) group, group treated with iTBS post EAE immunization (EAE + iTBS), group treated with cTBS post EAE immunization (EAE + cTBS), group of healthy animals treated with iTBS or cTBS. Therapeutic protocols of iTBS or cTBS in all EAE groups of animals were performed starting from 14 days post immunization (dpi), for 10 days with time point decapitation at 24 dpi. After decapitation, spinal cords were analysed for BDNF and Ki67 expression. The results revealed reduced BDNF expression in the rat's spinal cord of EAE animals in the stage of remission, which was associated with increased Ki67 and GFAP expressions. Decreased Iba 1 and BDNF expression, contrary to increased Iba 1 and Ki67 expression, suggests clustered microglia in the resolution phase of EAE. Enhanced GABA expression in spinal cord sections indicates higher GABA metabolic turnover, and also GAD activity in astrocytes, or prominent activity of GABAergic neurons. Both TBS protocols induced advance BDNF expression; amongst iTBS application provoked elevating of BDNF and stabilizing of GFAP and Ki67 expressions.",
journal = "Folia Neuropathologica",
title = "Theta burst stimulation influence the expression of BDNF in the spinal cord on the experimental autoimmune encephalomyelitis.",
number = "2",
volume = "57",
doi = "10.5114/fn.2019.86294",
pages = "129-145"
}

Stevanović, I., Mančić, B., Ilić, T., Milosavljević, P., Lavrnja, I., Stojanović, I.,& Ninković, M.. (2019). Theta burst stimulation influence the expression of BDNF in the spinal cord on the experimental autoimmune encephalomyelitis.. in Folia Neuropathologica, 57(2), 129-145.
https://doi.org/10.5114/fn.2019.86294

Stevanović I, Mančić B, Ilić T, Milosavljević P, Lavrnja I, Stojanović I, Ninković M. Theta burst stimulation influence the expression of BDNF in the spinal cord on the experimental autoimmune encephalomyelitis.. in Folia Neuropathologica. 2019;57(2):129-145.
doi:10.5114/fn.2019.86294 .

Stevanović, Ivana, Mančić, Bojana, Ilić, Tihomir, Milosavljević, Petar, Lavrnja, Irena, Stojanović, Ivana, Ninković, Milica, "Theta burst stimulation influence the expression of BDNF in the spinal cord on the experimental autoimmune encephalomyelitis." in Folia Neuropathologica, 57, no. 2 (2019):129-145,
https://doi.org/10.5114/fn.2019.86294 . .

TY  - JOUR
AU  - Dejanović, Bratislav
AU  - Vuković-Dejanović, Vesna
AU  - Ninković, Milica
AU  - Lavrnja, Irena
AU  - Stojanović, Ivana
AU  - Pavlović, Miloš
AU  - Begović, Vesna
AU  - Mirković, Duško
AU  - Stevanović, Ivana
PY  - 2018
UR  - https://actavet.vfu.cz/87/2/0145/
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3097
AB  - This study was aimed to study the potentially beneficial effects of agmatine on oxidative/nitrosative stress development in the brain of Wistar rats during subacute chlorpromazine treatment. The animals were divided into control (0.9% saline), chlorpromazine (38.7 mg/kg b.w.), chlorpromazine+agmatine (agmatine 75 mg/kg b.w. immediately after chlorpromazine, 38.7 mg/kg b.w. i.p.) and agmatine (75 mg/kg b.w.) groups. All the tested substances were administered intraperitoneally for 15 consecutive days and the rats were sacrificed by decapitation on day 15. Subacute administration of chlorpromazine resulted in increased lipid peroxidation, nitric oxide concentration and superoxide anion production, while completely damaging the antioxidant defence system in the cerebral cortex, striatum, and hippocampus. However, the combined treatment with chlorpromazine and agmatine significantly attenuated the oxidative/nitrosative stress indices and restored the antioxidant capacity to the control values in all of the examined brain regions. Western blot analysis supported biochemical findings in all groups, but the most notable changes were found in the hippocampus. Our results suggest potentially beneficial effects of agmatine, which may be useful in the modified antioxidant approach in chlorpromazine-therapy.
T2  - Acta Veterinaria Brno
T1  - Effects of agmatine on chlorpromazine-induced neuronal injury in rat
IS  - 2
VL  - 87
DO  - 10.2754/avb201887020145
DO  - 0001-7213
SP  - 145
EP  - 153
ER  - 

@article{
author = "Dejanović, Bratislav and Vuković-Dejanović, Vesna and Ninković, Milica and Lavrnja, Irena and Stojanović, Ivana and Pavlović, Miloš and Begović, Vesna and Mirković, Duško and Stevanović, Ivana",
year = "2018",
abstract = "This study was aimed to study the potentially beneficial effects of agmatine on oxidative/nitrosative stress development in the brain of Wistar rats during subacute chlorpromazine treatment. The animals were divided into control (0.9% saline), chlorpromazine (38.7 mg/kg b.w.), chlorpromazine+agmatine (agmatine 75 mg/kg b.w. immediately after chlorpromazine, 38.7 mg/kg b.w. i.p.) and agmatine (75 mg/kg b.w.) groups. All the tested substances were administered intraperitoneally for 15 consecutive days and the rats were sacrificed by decapitation on day 15. Subacute administration of chlorpromazine resulted in increased lipid peroxidation, nitric oxide concentration and superoxide anion production, while completely damaging the antioxidant defence system in the cerebral cortex, striatum, and hippocampus. However, the combined treatment with chlorpromazine and agmatine significantly attenuated the oxidative/nitrosative stress indices and restored the antioxidant capacity to the control values in all of the examined brain regions. Western blot analysis supported biochemical findings in all groups, but the most notable changes were found in the hippocampus. Our results suggest potentially beneficial effects of agmatine, which may be useful in the modified antioxidant approach in chlorpromazine-therapy.",
journal = "Acta Veterinaria Brno",
title = "Effects of agmatine on chlorpromazine-induced neuronal injury in rat",
number = "2",
volume = "87",
doi = "10.2754/avb201887020145, 0001-7213",
pages = "145-153"
}

Dejanović, B., Vuković-Dejanović, V., Ninković, M., Lavrnja, I., Stojanović, I., Pavlović, M., Begović, V., Mirković, D.,& Stevanović, I.. (2018). Effects of agmatine on chlorpromazine-induced neuronal injury in rat. in Acta Veterinaria Brno, 87(2), 145-153.
https://doi.org/10.2754/avb201887020145

Dejanović B, Vuković-Dejanović V, Ninković M, Lavrnja I, Stojanović I, Pavlović M, Begović V, Mirković D, Stevanović I. Effects of agmatine on chlorpromazine-induced neuronal injury in rat. in Acta Veterinaria Brno. 2018;87(2):145-153.
doi:10.2754/avb201887020145 .

Dejanović, Bratislav, Vuković-Dejanović, Vesna, Ninković, Milica, Lavrnja, Irena, Stojanović, Ivana, Pavlović, Miloš, Begović, Vesna, Mirković, Duško, Stevanović, Ivana, "Effects of agmatine on chlorpromazine-induced neuronal injury in rat" in Acta Veterinaria Brno, 87, no. 2 (2018):145-153,
https://doi.org/10.2754/avb201887020145 . .

TY  - CONF
AU  - Milićević, Katarina
AU  - Milošević, Milena
AU  - Božić, Iva
AU  - Lavrnja, Irena
AU  - Stevanović, Ivana
AU  - Bijelić, Dunja D.
AU  - Živković, Irena
AU  - Stević, Zorica
AU  - Anđus, Pavle R.
PY  - 2017
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5990
AB  - Introduction. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that affects motor neurons. Having in mind well documented facts that on one hand, ALS brain is under oxidative stress, and on the other that non-cell autonomous mechanisms involving glial cells contribute to the disease progression, we wanted to examine the effect of humoral factors immunoglobulins G from ALS patients (ALS IgG) on oxidative stress and antioxidative system of BV-2 microglial cell line. Methods. BV-2 cells were treated with ALS and control IgG (0.1 mg/ml). TNF-α release, oxidative stress markers and antioxidative enzymes activities were determined using biochemical assays (24 h treatment), while gene expression was determined using RT-qPCR (4 h treatment). ROS, cytosolic peroxide and pH alteration were evaluated with carboxy-H2DCFDA, HyPer and SypHer, respectively. Results. All tested ALS IgG (compared with control IgG) induced oxidative stress (rise in NO and lipid peroxidation), release of TNF-α and higher antioxidative defense (elevation of Mn- and Cu,Zn-superoxide dismutase, catalase, glutathione reductase with a decrease of glutathione peroxidase and glutathione). IgG from 4/11 ALS patients induced slow exponential rise of HyPer intensity and lower increase of SypHer intensity. None of the control IgG induced changes with neither of the indicators. Acute ROS generation was detected in 1/3 of ALS samples with carboxy-H2DCFDA. Conclusion. Our study demonstrates the potential role of inflammatory humoral factors, ALS IgGs, as triggers (via ROS generation) of the activation in microglia, known to occur in later stages of the disease.
PB  - Belgrade: Serbian Neuroscience Society
C3  - Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia
T1  - Serum IGG fraction from ALS patients alters redox homeostasis in the BV-2 microglial cell line
SP  - 72
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_5990
ER  - 

@conference{
author = "Milićević, Katarina and Milošević, Milena and Božić, Iva and Lavrnja, Irena and Stevanović, Ivana and Bijelić, Dunja D. and Živković, Irena and Stević, Zorica and Anđus, Pavle R.",
year = "2017",
abstract = "Introduction. Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder that affects motor neurons. Having in mind well documented facts that on one hand, ALS brain is under oxidative stress, and on the other that non-cell autonomous mechanisms involving glial cells contribute to the disease progression, we wanted to examine the effect of humoral factors immunoglobulins G from ALS patients (ALS IgG) on oxidative stress and antioxidative system of BV-2 microglial cell line. Methods. BV-2 cells were treated with ALS and control IgG (0.1 mg/ml). TNF-α release, oxidative stress markers and antioxidative enzymes activities were determined using biochemical assays (24 h treatment), while gene expression was determined using RT-qPCR (4 h treatment). ROS, cytosolic peroxide and pH alteration were evaluated with carboxy-H2DCFDA, HyPer and SypHer, respectively. Results. All tested ALS IgG (compared with control IgG) induced oxidative stress (rise in NO and lipid peroxidation), release of TNF-α and higher antioxidative defense (elevation of Mn- and Cu,Zn-superoxide dismutase, catalase, glutathione reductase with a decrease of glutathione peroxidase and glutathione). IgG from 4/11 ALS patients induced slow exponential rise of HyPer intensity and lower increase of SypHer intensity. None of the control IgG induced changes with neither of the indicators. Acute ROS generation was detected in 1/3 of ALS samples with carboxy-H2DCFDA. Conclusion. Our study demonstrates the potential role of inflammatory humoral factors, ALS IgGs, as triggers (via ROS generation) of the activation in microglia, known to occur in later stages of the disease.",
publisher = "Belgrade: Serbian Neuroscience Society",
journal = "Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia",
title = "Serum IGG fraction from ALS patients alters redox homeostasis in the BV-2 microglial cell line",
pages = "72",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_5990"
}

Milićević, K., Milošević, M., Božić, I., Lavrnja, I., Stevanović, I., Bijelić, D. D., Živković, I., Stević, Z.,& Anđus, P. R.. (2017). Serum IGG fraction from ALS patients alters redox homeostasis in the BV-2 microglial cell line. in Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia
Belgrade: Serbian Neuroscience Society., 72.
https://hdl.handle.net/21.15107/rcub_ibiss_5990

Milićević K, Milošević M, Božić I, Lavrnja I, Stevanović I, Bijelić DD, Živković I, Stević Z, Anđus PR. Serum IGG fraction from ALS patients alters redox homeostasis in the BV-2 microglial cell line. in Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia. 2017;:72.
https://hdl.handle.net/21.15107/rcub_ibiss_5990 .

Milićević, Katarina, Milošević, Milena, Božić, Iva, Lavrnja, Irena, Stevanović, Ivana, Bijelić, Dunja D., Živković, Irena, Stević, Zorica, Anđus, Pavle R., "Serum IGG fraction from ALS patients alters redox homeostasis in the BV-2 microglial cell line" in Book of Abstract: 7th Congress of Serbian Neuroscience Society with international participation; 2017 Oct 25-27; Belgrade, Serbia (2017):72,
https://hdl.handle.net/21.15107/rcub_ibiss_5990 .

TY  - JOUR
AU  - Dejanović, Bratislav
AU  - Lavrnja, Irena
AU  - Ninković, Milica
AU  - Stojanović, Ivana
AU  - Đurić, Ana
AU  - Dilber, Sanda
AU  - Stevanović, Ivana
PY  - 2017
UR  - https://www.jstage.jst.go.jp/article/expanim/66/1/66_16-0010/_article
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2562
AB  - Chlorpromazine (CPZ) is a member of a widely used class of antipsychotic agents. The metabolic pathways of CPZ toxicity were examined by monitoring oxidative/nitrosative stress markers. The aim of the study was to investigate the hypothesis that agmatine (AGM) prevents oxidative stress in the liver of Wistar rats 48 h after administration of CPZ. All tested compounds were administered intraperitoneally (i.p.) in one single dose. The animals were divided into control (C, 0.9% saline solution), CPZ (CPZ, 38.7 mg/kg b.w.), CPZ+AGM (AGM, 75 mg/kg b.w. immediately after CPZ, 38.7 mg/kg b.w. i.p.), and AGM (AGM, 75 mg/kg b.w.) groups. Rats were sacrificed by decapitation 48 h after treatment. The CPZ and CPZ+AGM treatments significantly increased thiobarbituric acid reactive substances (TBARS), the nitrite and nitrate (NO2+NO3) concentration, and superoxide anion (O2 •-) production in rat liver homogenates compared with C values. CPZ injection decreased the capacity of the antioxidant defense system: superoxide dismutase (SOD) activity, catalase (CAT) activity, total glutathione (GSH) content, glutathione peroxidase (GPx) activity, and glutathione reductase (GR) activity compared with the values of the C group. However, treatment with AGM increased antioxidant capacity in the rat liver; it increased the CAT activity, GSH concentration, GPx activity, and GR activity compared with the values of the CPZ rats. Immunohistochemical staining of ED1 in rats showed an increase in the number of positive cells 48 h after acute CPZ administration compared with the C group. Our results showed that AGM has no protective effects on parameters of oxidative and/or nitrosative stress in the liver but that it absolutely protective effects on the antioxidant defense system and restores the antioxidant capacity in liver tissue after administration of CPZ.
T2  - Experimental Animals
T1  - Effects of agmatine on chlorpromazine toxicity in the liver of Wistar rats: the possible role of oxidant/antioxidant imbalance
IS  - 1
VL  - 66
DO  - 10.1538/expanim.16-0010
SP  - 17
EP  - 27
ER  - 

@article{
author = "Dejanović, Bratislav and Lavrnja, Irena and Ninković, Milica and Stojanović, Ivana and Đurić, Ana and Dilber, Sanda and Stevanović, Ivana",
year = "2017",
abstract = "Chlorpromazine (CPZ) is a member of a widely used class of antipsychotic agents. The metabolic pathways of CPZ toxicity were examined by monitoring oxidative/nitrosative stress markers. The aim of the study was to investigate the hypothesis that agmatine (AGM) prevents oxidative stress in the liver of Wistar rats 48 h after administration of CPZ. All tested compounds were administered intraperitoneally (i.p.) in one single dose. The animals were divided into control (C, 0.9% saline solution), CPZ (CPZ, 38.7 mg/kg b.w.), CPZ+AGM (AGM, 75 mg/kg b.w. immediately after CPZ, 38.7 mg/kg b.w. i.p.), and AGM (AGM, 75 mg/kg b.w.) groups. Rats were sacrificed by decapitation 48 h after treatment. The CPZ and CPZ+AGM treatments significantly increased thiobarbituric acid reactive substances (TBARS), the nitrite and nitrate (NO2+NO3) concentration, and superoxide anion (O2 •-) production in rat liver homogenates compared with C values. CPZ injection decreased the capacity of the antioxidant defense system: superoxide dismutase (SOD) activity, catalase (CAT) activity, total glutathione (GSH) content, glutathione peroxidase (GPx) activity, and glutathione reductase (GR) activity compared with the values of the C group. However, treatment with AGM increased antioxidant capacity in the rat liver; it increased the CAT activity, GSH concentration, GPx activity, and GR activity compared with the values of the CPZ rats. Immunohistochemical staining of ED1 in rats showed an increase in the number of positive cells 48 h after acute CPZ administration compared with the C group. Our results showed that AGM has no protective effects on parameters of oxidative and/or nitrosative stress in the liver but that it absolutely protective effects on the antioxidant defense system and restores the antioxidant capacity in liver tissue after administration of CPZ.",
journal = "Experimental Animals",
title = "Effects of agmatine on chlorpromazine toxicity in the liver of Wistar rats: the possible role of oxidant/antioxidant imbalance",
number = "1",
volume = "66",
doi = "10.1538/expanim.16-0010",
pages = "17-27"
}

Dejanović, B., Lavrnja, I., Ninković, M., Stojanović, I., Đurić, A., Dilber, S.,& Stevanović, I.. (2017). Effects of agmatine on chlorpromazine toxicity in the liver of Wistar rats: the possible role of oxidant/antioxidant imbalance. in Experimental Animals, 66(1), 17-27.
https://doi.org/10.1538/expanim.16-0010

Dejanović B, Lavrnja I, Ninković M, Stojanović I, Đurić A, Dilber S, Stevanović I. Effects of agmatine on chlorpromazine toxicity in the liver of Wistar rats: the possible role of oxidant/antioxidant imbalance. in Experimental Animals. 2017;66(1):17-27.
doi:10.1538/expanim.16-0010 .

Dejanović, Bratislav, Lavrnja, Irena, Ninković, Milica, Stojanović, Ivana, Đurić, Ana, Dilber, Sanda, Stevanović, Ivana, "Effects of agmatine on chlorpromazine toxicity in the liver of Wistar rats: the possible role of oxidant/antioxidant imbalance" in Experimental Animals, 66, no. 1 (2017):17-27,
https://doi.org/10.1538/expanim.16-0010 . .

TY  - JOUR
AU  - Milošević, Milena
AU  - Milićević, Katarina
AU  - Božić, Iva
AU  - Lavrnja, Irena
AU  - Stevanović, Ivana
AU  - Bijelić, Dunja
AU  - Dubaić, Marija
AU  - Živković, Irena
AU  - Stević, Zorica
AU  - Giniatullin, Rashid
AU  - Andjus, Pavle
PY  - 2017
UR  - http://journal.frontiersin.org/article/10.3389/fimmu.2017.01619/full
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2928
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with a very fast progression, no diagnostic tool for the presymptomatic phase, and still no effective treatment of the disease. Although ALS affects motor neurons, the overall pathophysiological condition points out to the non-cell autonomous mechanisms, where astrocytes and microglia play crucial roles in the disease progression. We have already shown that IgG from sera of ALS patients (ALS IgG) induce calcium transients and an increase in the mobility of acidic vesicles in cultured rat astrocytes. Having in mind the role of microglia in neurodegeneration, and a well-documented fact that oxidative stress is one of the many components contributing to the disease, we decided to examine the effect of ALS IgG on activation, oxidative stress and antioxidative system of BV-2 microglia, and to evaluate their acute effect on cytosolic peroxide, pH, and on reactive oxygen species (ROS) generation. All tested ALS IgGs (compared to control IgG) induced oxidative stress (rise in nitric oxide and the index of lipid peroxidation) followed by release of TNF-α and higher antioxidative defense (elevation of Mn- and CuZn-superoxide dismutase, catalase, and glutathione reductase with a decrease of glutathione peroxidase and glutathione) after 24 h treatment. Both ALS IgG and control IgG showed same localization on the membrane of BV-2 cells following 24 h treatment. Cytosolic peroxide and pH alteration were evaluated with fluorescent probes HyPer and SypHer, respectively, having in mind that HyPer also reacts to pH changes. Out of 11 tested IgGs from ALS patients, 4 induced slow exponential rise of HyPer signal, with maximal normalized fluorescence in the range 0.2–0.5, also inducing similar increase of SypHer intensity, but of a lower amplitude. None of the control IgGs induced changes with neither of the indicators. Acute ROS generation was detected in one out of three tested ALS samples with carboxy-H2DCFDA. The observed phenomena demonstrate the potential role of inflammatory humoral factors, IgGs, as potential triggers of the activation in microglia, known to occur in later stages of ALS. Therefore, revealing the ALS IgG signaling cascade in microglial cells could offer a valuable molecular biomarker and/or a potential therapeutic target.
T2  - Frontiers in Immunology
T1  - Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce Oxidative Stress and Upregulation of Antioxidative System in BV-2 Microglial Cell Line
IS  - NOV
VL  - 8
DO  - 10.3389/fimmu.2017.01619
SP  - 1619
ER  - 

@article{
author = "Milošević, Milena and Milićević, Katarina and Božić, Iva and Lavrnja, Irena and Stevanović, Ivana and Bijelić, Dunja and Dubaić, Marija and Živković, Irena and Stević, Zorica and Giniatullin, Rashid and Andjus, Pavle",
year = "2017",
abstract = "Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with a very fast progression, no diagnostic tool for the presymptomatic phase, and still no effective treatment of the disease. Although ALS affects motor neurons, the overall pathophysiological condition points out to the non-cell autonomous mechanisms, where astrocytes and microglia play crucial roles in the disease progression. We have already shown that IgG from sera of ALS patients (ALS IgG) induce calcium transients and an increase in the mobility of acidic vesicles in cultured rat astrocytes. Having in mind the role of microglia in neurodegeneration, and a well-documented fact that oxidative stress is one of the many components contributing to the disease, we decided to examine the effect of ALS IgG on activation, oxidative stress and antioxidative system of BV-2 microglia, and to evaluate their acute effect on cytosolic peroxide, pH, and on reactive oxygen species (ROS) generation. All tested ALS IgGs (compared to control IgG) induced oxidative stress (rise in nitric oxide and the index of lipid peroxidation) followed by release of TNF-α and higher antioxidative defense (elevation of Mn- and CuZn-superoxide dismutase, catalase, and glutathione reductase with a decrease of glutathione peroxidase and glutathione) after 24 h treatment. Both ALS IgG and control IgG showed same localization on the membrane of BV-2 cells following 24 h treatment. Cytosolic peroxide and pH alteration were evaluated with fluorescent probes HyPer and SypHer, respectively, having in mind that HyPer also reacts to pH changes. Out of 11 tested IgGs from ALS patients, 4 induced slow exponential rise of HyPer signal, with maximal normalized fluorescence in the range 0.2–0.5, also inducing similar increase of SypHer intensity, but of a lower amplitude. None of the control IgGs induced changes with neither of the indicators. Acute ROS generation was detected in one out of three tested ALS samples with carboxy-H2DCFDA. The observed phenomena demonstrate the potential role of inflammatory humoral factors, IgGs, as potential triggers of the activation in microglia, known to occur in later stages of ALS. Therefore, revealing the ALS IgG signaling cascade in microglial cells could offer a valuable molecular biomarker and/or a potential therapeutic target.",
journal = "Frontiers in Immunology",
title = "Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce Oxidative Stress and Upregulation of Antioxidative System in BV-2 Microglial Cell Line",
number = "NOV",
volume = "8",
doi = "10.3389/fimmu.2017.01619",
pages = "1619"
}

Milošević, M., Milićević, K., Božić, I., Lavrnja, I., Stevanović, I., Bijelić, D., Dubaić, M., Živković, I., Stević, Z., Giniatullin, R.,& Andjus, P.. (2017). Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce Oxidative Stress and Upregulation of Antioxidative System in BV-2 Microglial Cell Line. in Frontiers in Immunology, 8(NOV), 1619.
https://doi.org/10.3389/fimmu.2017.01619

Milošević M, Milićević K, Božić I, Lavrnja I, Stevanović I, Bijelić D, Dubaić M, Živković I, Stević Z, Giniatullin R, Andjus P. Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce Oxidative Stress and Upregulation of Antioxidative System in BV-2 Microglial Cell Line. in Frontiers in Immunology. 2017;8(NOV):1619.
doi:10.3389/fimmu.2017.01619 .

Milošević, Milena, Milićević, Katarina, Božić, Iva, Lavrnja, Irena, Stevanović, Ivana, Bijelić, Dunja, Dubaić, Marija, Živković, Irena, Stević, Zorica, Giniatullin, Rashid, Andjus, Pavle, "Immunoglobulins G from Sera of Amyotrophic Lateral Sclerosis Patients Induce Oxidative Stress and Upregulation of Antioxidative System in BV-2 Microglial Cell Line" in Frontiers in Immunology, 8, no. NOV (2017):1619,
https://doi.org/10.3389/fimmu.2017.01619 . .

TY  - JOUR
AU  - Adžić, Marija
AU  - Stevanović, Ivana
AU  - Josipović, Nataša
AU  - Laketa, Danijela
AU  - Lavrnja, Irena
AU  - Bjelobaba, Ivana
AU  - Božić, Iva
AU  - Jovanović, Marija
AU  - Milošević, Milena
AU  - Nedeljković, Nadežda
PY  - 2017
UR  - http://doi.wiley.com/10.1002/jnr.23950
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2560
AB  - It is widely accepted that adenosine triphosphate (ATP) acts as a universal danger-associated molecular pattern with several known mechanisms for immune cell activation. In the central nervous system, ATP activates microglia and astrocytes and induces a neuroinflammatory response. The aim of the present study was to describe responses of isolated astrocytes to increasing concentrations of ATP (5 µM to 1 mM), which were intended to mimic graded intensity of the extracellular stimulus. The results show that ATP induces graded activation response of astrocytes in terms of the cell proliferation, stellation, shape remodeling, and underlying actin and GFAP filament rearrangement, although the changes occurred without an apparent increase in GFAP and actin protein expression. On the other hand, ATP in the range of applied concentrations did not evoke IL-1β release from cultured astrocytes, nor did it modify the release from LPS and LPS+IFN-γ–primed astrocytes. ATP did not promote astrocyte migration in the wound-healing assay, nor did it increase production of reactive oxygen and nitrogen species and lipid peroxidation. Instead, ATP strengthened the antioxidative defense of astrocytes by inducing Cu/ZnSOD and MnSOD activities and by increasing their glutathione content. Our current results suggest that although ATP triggers several attributes of activated astrocytic phenotype with a magnitude that increases with the concentration, it is not sufficient to induce full-blown reactive phenotype of astrocytes in vitro. © 2016 Wiley Periodicals, Inc.
T2  - Journal of Neuroscience Research
T1  - Extracellular ATP induces graded reactive response of astrocytes and strengthens their antioxidative defense in vitro
IS  - 4
VL  - 95
DO  - 10.1002/jnr.23950
SP  - 1053
EP  - 1066
ER  - 

@article{
author = "Adžić, Marija and Stevanović, Ivana and Josipović, Nataša and Laketa, Danijela and Lavrnja, Irena and Bjelobaba, Ivana and Božić, Iva and Jovanović, Marija and Milošević, Milena and Nedeljković, Nadežda",
year = "2017",
abstract = "It is widely accepted that adenosine triphosphate (ATP) acts as a universal danger-associated molecular pattern with several known mechanisms for immune cell activation. In the central nervous system, ATP activates microglia and astrocytes and induces a neuroinflammatory response. The aim of the present study was to describe responses of isolated astrocytes to increasing concentrations of ATP (5 µM to 1 mM), which were intended to mimic graded intensity of the extracellular stimulus. The results show that ATP induces graded activation response of astrocytes in terms of the cell proliferation, stellation, shape remodeling, and underlying actin and GFAP filament rearrangement, although the changes occurred without an apparent increase in GFAP and actin protein expression. On the other hand, ATP in the range of applied concentrations did not evoke IL-1β release from cultured astrocytes, nor did it modify the release from LPS and LPS+IFN-γ–primed astrocytes. ATP did not promote astrocyte migration in the wound-healing assay, nor did it increase production of reactive oxygen and nitrogen species and lipid peroxidation. Instead, ATP strengthened the antioxidative defense of astrocytes by inducing Cu/ZnSOD and MnSOD activities and by increasing their glutathione content. Our current results suggest that although ATP triggers several attributes of activated astrocytic phenotype with a magnitude that increases with the concentration, it is not sufficient to induce full-blown reactive phenotype of astrocytes in vitro. © 2016 Wiley Periodicals, Inc.",
journal = "Journal of Neuroscience Research",
title = "Extracellular ATP induces graded reactive response of astrocytes and strengthens their antioxidative defense in vitro",
number = "4",
volume = "95",
doi = "10.1002/jnr.23950",
pages = "1053-1066"
}

Adžić, M., Stevanović, I., Josipović, N., Laketa, D., Lavrnja, I., Bjelobaba, I., Božić, I., Jovanović, M., Milošević, M.,& Nedeljković, N.. (2017). Extracellular ATP induces graded reactive response of astrocytes and strengthens their antioxidative defense in vitro. in Journal of Neuroscience Research, 95(4), 1053-1066.
https://doi.org/10.1002/jnr.23950

Adžić M, Stevanović I, Josipović N, Laketa D, Lavrnja I, Bjelobaba I, Božić I, Jovanović M, Milošević M, Nedeljković N. Extracellular ATP induces graded reactive response of astrocytes and strengthens their antioxidative defense in vitro. in Journal of Neuroscience Research. 2017;95(4):1053-1066.
doi:10.1002/jnr.23950 .

Adžić, Marija, Stevanović, Ivana, Josipović, Nataša, Laketa, Danijela, Lavrnja, Irena, Bjelobaba, Ivana, Božić, Iva, Jovanović, Marija, Milošević, Milena, Nedeljković, Nadežda, "Extracellular ATP induces graded reactive response of astrocytes and strengthens their antioxidative defense in vitro" in Journal of Neuroscience Research, 95, no. 4 (2017):1053-1066,
https://doi.org/10.1002/jnr.23950 . .

TY  - JOUR
AU  - Dejanović, Bratislav
AU  - Stevanović, Ivana
AU  - Ninković, Milica
AU  - Stojanović, Ivana
AU  - Lavrnja, Irena
AU  - Radičević, Tatjana
PY  - 2016
UR  - http://www.scopus.com/inward/record.url?eid=2-s2.0-84964311353&partnerID=tZOtx3y1
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2531
AB  - Summary The metabolic pathways of chlorpromazine (CPZ) toxicity were tracked by assessing oxidative/nitrosative stress markers. The main objective of the study was to test the hypothesis that agmatine (AGM) prevents oxidative/nitrosative stress in the liver of Wistar rats 15 days after administration of CPZ. All tested substances were administered intraperitoneally (i.p.) for 15 consecutive days. The rats were divided into four groups: the control group (C, 0.9 % saline solution), the CPZ group (CPZ, 38.7 mg/kg b.w.), the CPZ+AGM group (AGM, 75 mg/kg b.w. immediately after CPZ, 38.7 mg/kg b.w. i.p.) and the AGM group (AGM, 75 mg/kg b.w.). Rats were decapitated 15 days after the appropriate treatment. In the CPZ group, CPZ concentration was significantly increased compared to C values (p<0.01), while AGM treatment induced the significant decrease in CPZ concentration in the CPZ+AGM group (p<0.05) and the AGM group (p<0.01). CPZ application to healthy rats did not lead to any changes of lipid peroxidation in the liver compared to the C group, but AGM treatment decreased that parameter compared to the CPZ group (p<0.05). In CPZ liver homogenates, nitrite and nitrate concentrations were increased compared to controls (p<0.001), and AGM treatment diminished that parameter in the CPZ group (p<0.05), as well as in the AGM group (p<0.001). In CPZ animals, glutathione level and catalase activity were decreased in comparison with C values (p<0.01 respectively), but AGM treatment increased the activity of catalase in comparison with CPZ animals (p<0.05 respectively). Western blot analysis supported biochemical findings in all groups. Our results showed that treatment with AGM significantly supressed the oxidative/nitrosative stress parameters and restored antioxidant defense in rat liver.
T2  - Acta Facultatis Medicae Naissensis
T1  - Protective effects of agmatine against chlorpromazine-induced toxicity in the liver of wistar rats
IS  - 1
VL  - 33
DO  - 10.1515/afmnai-2016-0002
SP  - 13
EP  - 22
ER  - 

@article{
author = "Dejanović, Bratislav and Stevanović, Ivana and Ninković, Milica and Stojanović, Ivana and Lavrnja, Irena and Radičević, Tatjana",
year = "2016",
abstract = "Summary The metabolic pathways of chlorpromazine (CPZ) toxicity were tracked by assessing oxidative/nitrosative stress markers. The main objective of the study was to test the hypothesis that agmatine (AGM) prevents oxidative/nitrosative stress in the liver of Wistar rats 15 days after administration of CPZ. All tested substances were administered intraperitoneally (i.p.) for 15 consecutive days. The rats were divided into four groups: the control group (C, 0.9 % saline solution), the CPZ group (CPZ, 38.7 mg/kg b.w.), the CPZ+AGM group (AGM, 75 mg/kg b.w. immediately after CPZ, 38.7 mg/kg b.w. i.p.) and the AGM group (AGM, 75 mg/kg b.w.). Rats were decapitated 15 days after the appropriate treatment. In the CPZ group, CPZ concentration was significantly increased compared to C values (p<0.01), while AGM treatment induced the significant decrease in CPZ concentration in the CPZ+AGM group (p<0.05) and the AGM group (p<0.01). CPZ application to healthy rats did not lead to any changes of lipid peroxidation in the liver compared to the C group, but AGM treatment decreased that parameter compared to the CPZ group (p<0.05). In CPZ liver homogenates, nitrite and nitrate concentrations were increased compared to controls (p<0.001), and AGM treatment diminished that parameter in the CPZ group (p<0.05), as well as in the AGM group (p<0.001). In CPZ animals, glutathione level and catalase activity were decreased in comparison with C values (p<0.01 respectively), but AGM treatment increased the activity of catalase in comparison with CPZ animals (p<0.05 respectively). Western blot analysis supported biochemical findings in all groups. Our results showed that treatment with AGM significantly supressed the oxidative/nitrosative stress parameters and restored antioxidant defense in rat liver.",
journal = "Acta Facultatis Medicae Naissensis",
title = "Protective effects of agmatine against chlorpromazine-induced toxicity in the liver of wistar rats",
number = "1",
volume = "33",
doi = "10.1515/afmnai-2016-0002",
pages = "13-22"
}

Dejanović, B., Stevanović, I., Ninković, M., Stojanović, I., Lavrnja, I.,& Radičević, T.. (2016). Protective effects of agmatine against chlorpromazine-induced toxicity in the liver of wistar rats. in Acta Facultatis Medicae Naissensis, 33(1), 13-22.
https://doi.org/10.1515/afmnai-2016-0002

Dejanović B, Stevanović I, Ninković M, Stojanović I, Lavrnja I, Radičević T. Protective effects of agmatine against chlorpromazine-induced toxicity in the liver of wistar rats. in Acta Facultatis Medicae Naissensis. 2016;33(1):13-22.
doi:10.1515/afmnai-2016-0002 .

Dejanović, Bratislav, Stevanović, Ivana, Ninković, Milica, Stojanović, Ivana, Lavrnja, Irena, Radičević, Tatjana, "Protective effects of agmatine against chlorpromazine-induced toxicity in the liver of wistar rats" in Acta Facultatis Medicae Naissensis, 33, no. 1 (2016):13-22,
https://doi.org/10.1515/afmnai-2016-0002 . .

TY  - JOUR
AU  - Stevanović, Ivana
AU  - Jovanović, Marina
AU  - Jelenković, Ankica V.
AU  - Bokonjić, D.
AU  - Čolić, M.
AU  - Stojanović, Ivana
AU  - Ninković, Milica
PY  - 2009
PY  - 2009
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/475
AB  - The present experiment was carried out to determine the effectiveness of nitric oxide synthase (NOS) inhibitor (L-NAME) in elevating the toxicity of AlCl3 on nitrite concentration and acetylcholine esterase activity of Wistar rats. Animals were killed 10 min and 3 days after the treatment and the forebrain cortex and striatum were removed. The results show that AlCl3 exposure promotes oxidative stress in different neural areas. The biochemical changes observed in neuronal tissues show that aluminium acts as a pro-oxidant, while NOS inhibitor exerts as antioxidant action in AlCl3-treated animals. In the present study, active avoidance learning was significantly impaired after AlCl3 injection, while pretreatment with L-NAME prevented the behavioural deficits caused between the 8th and 12th day after intrahippocampal application of neurotoxin. Our data suggest that aluminium may cause learning and memory deficits, while the treatment with L-NAME may decrease the oxidative stress and prevent learning and memory deficits caused by AlCl3.
AB  - U eksperimentu je ispitivana efikasnost inhibitora azot oksid sintaze (NOS)- L-NAME na toksičnost AlCl3 i određivana koncentracija nitrita i aktivnost acetilholin esteraze kod Wistar pacova. Životinje su dekapitovane 10 minuta ili 3 dana nakon tretmana i izolovani su kora prednjeg mozga i strijatum. Rezultati ukazuju da AlCl3 pokreće oksidativni stres u različitim regionima mozga. Biohemijske promene opisane u neuronskom tkivu ukazuju da aluminijum deluje kao prooksidans, dok inhibitor NOS ima antioksidativno dejstvo kod životinja tretiranih AlCl3. Reakcija aktivnog izbegavanja je bila znatno poremećena nakon aplikacije AlCl3, dok se davanjem L-NAME sprečavaju poremećaji ponašanja uzrokovani između 8. i 12. dana posle intrahipokampusne primene neurotoksina. Naši rezultati ukazuju da aluminijum može dovesti do smetnji u procesima učenja i pamćenja, dok tretman sa L-NAME smanjuje oksidativni stres i sprečava promene u učenju i pamćenju uzrokovane AlCl3.
T2  - Acta veterinaria
T1  - Efekat L-NAME na AlCl3-indukovanu toksičnost u mozgu pacova
T1  - Effect of L-NAME on AlCl3-induced toxicity in rat brain
IS  - 2-3
VL  - 59
DO  - 10.2298/AVB0903133S
SP  - 133
EP  - 146
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_475
ER  - 

@article{
author = "Stevanović, Ivana and Jovanović, Marina and Jelenković, Ankica V. and Bokonjić, D. and Čolić, M. and Stojanović, Ivana and Ninković, Milica",
year = "2009, 2009",
abstract = "The present experiment was carried out to determine the effectiveness of nitric oxide synthase (NOS) inhibitor (L-NAME) in elevating the toxicity of AlCl3 on nitrite concentration and acetylcholine esterase activity of Wistar rats. Animals were killed 10 min and 3 days after the treatment and the forebrain cortex and striatum were removed. The results show that AlCl3 exposure promotes oxidative stress in different neural areas. The biochemical changes observed in neuronal tissues show that aluminium acts as a pro-oxidant, while NOS inhibitor exerts as antioxidant action in AlCl3-treated animals. In the present study, active avoidance learning was significantly impaired after AlCl3 injection, while pretreatment with L-NAME prevented the behavioural deficits caused between the 8th and 12th day after intrahippocampal application of neurotoxin. Our data suggest that aluminium may cause learning and memory deficits, while the treatment with L-NAME may decrease the oxidative stress and prevent learning and memory deficits caused by AlCl3., U eksperimentu je ispitivana efikasnost inhibitora azot oksid sintaze (NOS)- L-NAME na toksičnost AlCl3 i određivana koncentracija nitrita i aktivnost acetilholin esteraze kod Wistar pacova. Životinje su dekapitovane 10 minuta ili 3 dana nakon tretmana i izolovani su kora prednjeg mozga i strijatum. Rezultati ukazuju da AlCl3 pokreće oksidativni stres u različitim regionima mozga. Biohemijske promene opisane u neuronskom tkivu ukazuju da aluminijum deluje kao prooksidans, dok inhibitor NOS ima antioksidativno dejstvo kod životinja tretiranih AlCl3. Reakcija aktivnog izbegavanja je bila znatno poremećena nakon aplikacije AlCl3, dok se davanjem L-NAME sprečavaju poremećaji ponašanja uzrokovani između 8. i 12. dana posle intrahipokampusne primene neurotoksina. Naši rezultati ukazuju da aluminijum može dovesti do smetnji u procesima učenja i pamćenja, dok tretman sa L-NAME smanjuje oksidativni stres i sprečava promene u učenju i pamćenju uzrokovane AlCl3.",
journal = "Acta veterinaria",
title = "Efekat L-NAME na AlCl3-indukovanu toksičnost u mozgu pacova, Effect of L-NAME on AlCl3-induced toxicity in rat brain",
number = "2-3",
volume = "59",
doi = "10.2298/AVB0903133S",
pages = "133-146",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_475"
}

Stevanović, I., Jovanović, M., Jelenković, A. V., Bokonjić, D., Čolić, M., Stojanović, I.,& Ninković, M.. (2009). Efekat L-NAME na AlCl3-indukovanu toksičnost u mozgu pacova. in Acta veterinaria, 59(2-3), 133-146.
https://doi.org/10.2298/AVB0903133S
https://hdl.handle.net/21.15107/rcub_ibiss_475

Stevanović I, Jovanović M, Jelenković AV, Bokonjić D, Čolić M, Stojanović I, Ninković M. Efekat L-NAME na AlCl3-indukovanu toksičnost u mozgu pacova. in Acta veterinaria. 2009;59(2-3):133-146.
doi:10.2298/AVB0903133S
https://hdl.handle.net/21.15107/rcub_ibiss_475 .

Stevanović, Ivana, Jovanović, Marina, Jelenković, Ankica V., Bokonjić, D., Čolić, M., Stojanović, Ivana, Ninković, Milica, "Efekat L-NAME na AlCl3-indukovanu toksičnost u mozgu pacova" in Acta veterinaria, 59, no. 2-3 (2009):133-146,
https://doi.org/10.2298/AVB0903133S .,
https://hdl.handle.net/21.15107/rcub_ibiss_475 .

TY  - JOUR
AU  - Stevanović, Ivana
AU  - Čolić, Miodrag
AU  - Jovanović, Marina
AU  - Jelenković, Ankica V.
AU  - Ninković, Milica I.
PY  - 2009
PY  - 2009
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/558
AB  - The present study was aimed at determining the effectiveness of nitric oxide synthase (NOS) inhibitors: N-nitro-L-arginine methyl ester, 7-nitroindazole and aminoguanidine in modulating the toxicity of AlCl3 on superoxide production and the malondialdehyde concentration of Wistar rats. The animals were sacrificed 10 min and 3 days after the treatment and the forebrain cortex was removed. The results show that AlCl3 exposure promotes oxidative stress in different neural areas. The biochemical changes observed in the neuronal tissues show that aluminum acts as pro-oxidant, while NOS inhibitors exert an anti-oxidant action in AlCl3-treated animals.
AB  - U eksperimentu je određivana efikasnost inhibitora azot-oksid-sintaze (NOS): metil-estra N-nitro-L-arginina, 7-nitroindazola i aminogvanidina u modulaciji toksičnosti AlCl3 na stvaranje superoksidnog anjona i koncentraciju malondialdehida kod Wistar pacova. Životinje su žrtvovane 10 min i 3 dana nakon tretmana i izolovana je kora velikog mozga. Rezultati pokazuju da izlaganje AlCl3 pokreće oksidativni stres u različitim moždanim regionima. Biohemijske promene opisane u neuronskom tkivu pokazuju da aluminijum deluje kao pro-oksidant, dok inhibitori NOS imaju antioksidativno dejstvo kod životinja tretiranih AlCl3.
T2  - Journal of the Serbian Chemical Society
T1  - Efekti različitih inhibitora azot-oksid-sintaze na oštećenje neurona izazvano AlCl3
T1  - Effects of various nitric oxide synthase inhibitors on AlCl3-induced neuronal injury in rats
IS  - 5
VL  - 74
SP  - 503
EP  - 511
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_558
ER  - 

@article{
author = "Stevanović, Ivana and Čolić, Miodrag and Jovanović, Marina and Jelenković, Ankica V. and Ninković, Milica I.",
year = "2009, 2009",
abstract = "The present study was aimed at determining the effectiveness of nitric oxide synthase (NOS) inhibitors: N-nitro-L-arginine methyl ester, 7-nitroindazole and aminoguanidine in modulating the toxicity of AlCl3 on superoxide production and the malondialdehyde concentration of Wistar rats. The animals were sacrificed 10 min and 3 days after the treatment and the forebrain cortex was removed. The results show that AlCl3 exposure promotes oxidative stress in different neural areas. The biochemical changes observed in the neuronal tissues show that aluminum acts as pro-oxidant, while NOS inhibitors exert an anti-oxidant action in AlCl3-treated animals., U eksperimentu je određivana efikasnost inhibitora azot-oksid-sintaze (NOS): metil-estra N-nitro-L-arginina, 7-nitroindazola i aminogvanidina u modulaciji toksičnosti AlCl3 na stvaranje superoksidnog anjona i koncentraciju malondialdehida kod Wistar pacova. Životinje su žrtvovane 10 min i 3 dana nakon tretmana i izolovana je kora velikog mozga. Rezultati pokazuju da izlaganje AlCl3 pokreće oksidativni stres u različitim moždanim regionima. Biohemijske promene opisane u neuronskom tkivu pokazuju da aluminijum deluje kao pro-oksidant, dok inhibitori NOS imaju antioksidativno dejstvo kod životinja tretiranih AlCl3.",
journal = "Journal of the Serbian Chemical Society",
title = "Efekti različitih inhibitora azot-oksid-sintaze na oštećenje neurona izazvano AlCl3, Effects of various nitric oxide synthase inhibitors on AlCl3-induced neuronal injury in rats",
number = "5",
volume = "74",
pages = "503-511",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_558"
}

Stevanović, I., Čolić, M., Jovanović, M., Jelenković, A. V.,& Ninković, M. I.. (2009). Efekti različitih inhibitora azot-oksid-sintaze na oštećenje neurona izazvano AlCl3. in Journal of the Serbian Chemical Society, 74(5), 503-511.
https://hdl.handle.net/21.15107/rcub_ibiss_558

Stevanović I, Čolić M, Jovanović M, Jelenković AV, Ninković MI. Efekti različitih inhibitora azot-oksid-sintaze na oštećenje neurona izazvano AlCl3. in Journal of the Serbian Chemical Society. 2009;74(5):503-511.
https://hdl.handle.net/21.15107/rcub_ibiss_558 .

Stevanović, Ivana, Čolić, Miodrag, Jovanović, Marina, Jelenković, Ankica V., Ninković, Milica I., "Efekti različitih inhibitora azot-oksid-sintaze na oštećenje neurona izazvano AlCl3" in Journal of the Serbian Chemical Society, 74, no. 5 (2009):503-511,
https://hdl.handle.net/21.15107/rcub_ibiss_558 .