TY  - JOUR
AU  - Ivković, Sanja
AU  - Major, Tamara
AU  - Mitić, Miloš
AU  - Lončarević-Vasiljković, Nataša
AU  - Jović, Milena
AU  - Adžić, Miroslav
PY  - 2022
UR  - https://linkinghub.elsevier.com/retrieve/pii/S0024320522001709
UR  - http://www.ncbi.nlm.nih.gov/pubmed/35283177
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/4942
AB  - The brain is the softest organ in the body, and any change in the mechanical properties of the tissue induces the activation of glial cells, astrocytes and microglia. Amyloid plaques, one of the main pathological features of Alzheimer's disease (AD), are substantially harder than the surrounding brain tissue and can activate astrocytes and microglia resulting in the glial engulfment of plaques. Durotaxis, a migratory preference towards stiffer tissue, is prompting microglia to form a mechanical barrier around plaques reducing amyloid β (Aβ) induced neurotoxicity. Mechanoreceptors are highly expressed in the brain, particularly in microglia. The large increase in the expression of the mechanoreceptor Piezo1 was observed in the brains from AD animal models and AD patients in plaque encompassing glia. Importantly, Piezo1 function is regulated via force-from-lipids through the lipid composition of the membrane and membranous incorporation of polyunsaturated fatty acids (PUFAs) can affect the function of Piezo1 altering mechanosensitive properties of the cell. On the other hand, PUFAs dietary supplementation can alter microglial polarization, the envelopment of amyloid plaques, and immune response and Piezo1 activity was implicated in the similar modulations of microglia behavior. Finally, PUFAs treatment is currently in use in medical trials as the therapy for sickle cell anemia, a disease linked with the mutations in Piezo1. Further studies are needed to elucidate the connection between PUFAs, Piezo1 expression, and microglia behavior in the AD brain. These findings could open new possibilities in harnessing microglia in AD and in developing novel therapeutic strategies.
T2  - Life sciences
T1  - Fatty acids as biomodulators of Piezo1 mediated glial mechanosensitivity in Alzheimer's disease.
VL  - 297
DO  - 10.1016/j.lfs.2022.120470
SP  - 120470
ER  - 

@article{
author = "Ivković, Sanja and Major, Tamara and Mitić, Miloš and Lončarević-Vasiljković, Nataša and Jović, Milena and Adžić, Miroslav",
year = "2022",
abstract = "The brain is the softest organ in the body, and any change in the mechanical properties of the tissue induces the activation of glial cells, astrocytes and microglia. Amyloid plaques, one of the main pathological features of Alzheimer's disease (AD), are substantially harder than the surrounding brain tissue and can activate astrocytes and microglia resulting in the glial engulfment of plaques. Durotaxis, a migratory preference towards stiffer tissue, is prompting microglia to form a mechanical barrier around plaques reducing amyloid β (Aβ) induced neurotoxicity. Mechanoreceptors are highly expressed in the brain, particularly in microglia. The large increase in the expression of the mechanoreceptor Piezo1 was observed in the brains from AD animal models and AD patients in plaque encompassing glia. Importantly, Piezo1 function is regulated via force-from-lipids through the lipid composition of the membrane and membranous incorporation of polyunsaturated fatty acids (PUFAs) can affect the function of Piezo1 altering mechanosensitive properties of the cell. On the other hand, PUFAs dietary supplementation can alter microglial polarization, the envelopment of amyloid plaques, and immune response and Piezo1 activity was implicated in the similar modulations of microglia behavior. Finally, PUFAs treatment is currently in use in medical trials as the therapy for sickle cell anemia, a disease linked with the mutations in Piezo1. Further studies are needed to elucidate the connection between PUFAs, Piezo1 expression, and microglia behavior in the AD brain. These findings could open new possibilities in harnessing microglia in AD and in developing novel therapeutic strategies.",
journal = "Life sciences",
title = "Fatty acids as biomodulators of Piezo1 mediated glial mechanosensitivity in Alzheimer's disease.",
volume = "297",
doi = "10.1016/j.lfs.2022.120470",
pages = "120470"
}

Ivković, S., Major, T., Mitić, M., Lončarević-Vasiljković, N., Jović, M.,& Adžić, M.. (2022). Fatty acids as biomodulators of Piezo1 mediated glial mechanosensitivity in Alzheimer's disease.. in Life sciences, 297, 120470.
https://doi.org/10.1016/j.lfs.2022.120470

Ivković S, Major T, Mitić M, Lončarević-Vasiljković N, Jović M, Adžić M. Fatty acids as biomodulators of Piezo1 mediated glial mechanosensitivity in Alzheimer's disease.. in Life sciences. 2022;297:120470.
doi:10.1016/j.lfs.2022.120470 .

Ivković, Sanja, Major, Tamara, Mitić, Miloš, Lončarević-Vasiljković, Nataša, Jović, Milena, Adžić, Miroslav, "Fatty acids as biomodulators of Piezo1 mediated glial mechanosensitivity in Alzheimer's disease." in Life sciences, 297 (2022):120470,
https://doi.org/10.1016/j.lfs.2022.120470 . .

TY  - JOUR
AU  - Radić, Ivan
AU  - Mirić, Mirjana
AU  - Mijović, Milica
AU  - Tatalović, Nikola
AU  - Mitić, Miloš
AU  - Nestorović, Vojkan
AU  - Adžić, Miroslav
AU  - Blagojević, Duško
AU  - Popović, Ljiljana
AU  - Janićijević Hudomal, Snežana
PY  - 2021
UR  - http://www.serbiosoc.org.rs/arch/index.php/abs/article/view/6170
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4181
AB  - Pumpkin seed oil (PSO) possesses a protective potential against liver injury due to the presence of biologically active ingredients. Adult male albino rats were administrated PSO (per os, 2 mL/kg b.w./day) and a 12% ethanol solution in water, ad libitum, with an average intake of 8.14 g of ethanol/kg bw/day for 6 weeks. Congestion, hepatic central vein dila-tion, portal vein branch dilation, Kupffer cell hyperplasia, fatty liver changes, hepatocyte focal necrosis were observed after daily alcohol intake. All observed changes were reduced when PSO was ingested with ethanol. PSO intake itself induced discrete cellular edema, congestion and slight dilatation of the central and portal vain branches. Chronic ethanol intake elevated catalase (CAT) activity and glutathione reductase (GR) protein expression; concomitant PSO intake had no effect on CAT activity or GR protein expression. PSO intake decreased the activities of GR, glutathione-S-transferase (GST) and xanthine oxidase (XOD) in the liver, probably due to the ingestion of antioxidants. Intake of PSO and ethanol significantly decreased cytosolic superoxide dismutase (SOD1) and increased NF-κB protein expression compared to ethanol intake, suggesting that the protective effects of PSO were mediated by the NF-κB signaling pathway. Our results reveal a therapeutic potential of PSO in alcoholic liver disease.
PB  - Serbian Biological Society
T2  - Archives of Biological Sciences
T1  - Protective effects of pumpkin (Cucurbita pepo L.) seed oil on rat liver damage induced by chronic alcohol consumption
IS  - 1
VL  - 73
DO  - 10.2298/ABS201205008R
SP  - 123
EP  - 133
ER  - 

@article{
author = "Radić, Ivan and Mirić, Mirjana and Mijović, Milica and Tatalović, Nikola and Mitić, Miloš and Nestorović, Vojkan and Adžić, Miroslav and Blagojević, Duško and Popović, Ljiljana and Janićijević Hudomal, Snežana",
year = "2021",
abstract = "Pumpkin seed oil (PSO) possesses a protective potential against liver injury due to the presence of biologically active ingredients. Adult male albino rats were administrated PSO (per os, 2 mL/kg b.w./day) and a 12% ethanol solution in water, ad libitum, with an average intake of 8.14 g of ethanol/kg bw/day for 6 weeks. Congestion, hepatic central vein dila-tion, portal vein branch dilation, Kupffer cell hyperplasia, fatty liver changes, hepatocyte focal necrosis were observed after daily alcohol intake. All observed changes were reduced when PSO was ingested with ethanol. PSO intake itself induced discrete cellular edema, congestion and slight dilatation of the central and portal vain branches. Chronic ethanol intake elevated catalase (CAT) activity and glutathione reductase (GR) protein expression; concomitant PSO intake had no effect on CAT activity or GR protein expression. PSO intake decreased the activities of GR, glutathione-S-transferase (GST) and xanthine oxidase (XOD) in the liver, probably due to the ingestion of antioxidants. Intake of PSO and ethanol significantly decreased cytosolic superoxide dismutase (SOD1) and increased NF-κB protein expression compared to ethanol intake, suggesting that the protective effects of PSO were mediated by the NF-κB signaling pathway. Our results reveal a therapeutic potential of PSO in alcoholic liver disease.",
publisher = "Serbian Biological Society",
journal = "Archives of Biological Sciences",
title = "Protective effects of pumpkin (Cucurbita pepo L.) seed oil on rat liver damage induced by chronic alcohol consumption",
number = "1",
volume = "73",
doi = "10.2298/ABS201205008R",
pages = "123-133"
}

Radić, I., Mirić, M., Mijović, M., Tatalović, N., Mitić, M., Nestorović, V., Adžić, M., Blagojević, D., Popović, L.,& Janićijević Hudomal, S.. (2021). Protective effects of pumpkin (Cucurbita pepo L.) seed oil on rat liver damage induced by chronic alcohol consumption. in Archives of Biological Sciences
Serbian Biological Society., 73(1), 123-133.
https://doi.org/10.2298/ABS201205008R

Radić I, Mirić M, Mijović M, Tatalović N, Mitić M, Nestorović V, Adžić M, Blagojević D, Popović L, Janićijević Hudomal S. Protective effects of pumpkin (Cucurbita pepo L.) seed oil on rat liver damage induced by chronic alcohol consumption. in Archives of Biological Sciences. 2021;73(1):123-133.
doi:10.2298/ABS201205008R .

Radić, Ivan, Mirić, Mirjana, Mijović, Milica, Tatalović, Nikola, Mitić, Miloš, Nestorović, Vojkan, Adžić, Miroslav, Blagojević, Duško, Popović, Ljiljana, Janićijević Hudomal, Snežana, "Protective effects of pumpkin (Cucurbita pepo L.) seed oil on rat liver damage induced by chronic alcohol consumption" in Archives of Biological Sciences, 73, no. 1 (2021):123-133,
https://doi.org/10.2298/ABS201205008R . .

TY  - DATA
AU  - Radić, Ivan
AU  - Mirić, Mirjana
AU  - Mijović, Milica
AU  - Tatalović, Nikola
AU  - Mitić, Miloš
AU  - Nestorović, Vojkan
AU  - Adžić, Miroslav
AU  - Blagojević, Duško
AU  - Popović, Ljiljana
AU  - Janićijević Hudomal, Snežana
PY  - 2021
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/4182
AB  - Supplementary Fig.S1. Scheme of the experimental design; Supplementary TableS2. Chemical analysis of commercialcold pressedpumpkin seed oil that was used in theexperiment.
PB  - Serbian Biological Society
T2  - Archives of Biological Sciences
T1  - Supplementary data for the article: Radic I, Miric M, Mijovic M, Tatalovic N, Mitic M, Nestorovic V, Adzic M, Blagojevic D, Popovic L, Janicijevic-Hudomal S. Protective effects of pumpkin (Cucurbita pepo L.) seed oil on rat liver damage induced by chronic alcohol consumption. Arch Biol Sci. 2021;73(1):123–33.
IS  - 1
VL  - 73
SP  - 123
EP  - 133
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_4182
ER  - 

@misc{
author = "Radić, Ivan and Mirić, Mirjana and Mijović, Milica and Tatalović, Nikola and Mitić, Miloš and Nestorović, Vojkan and Adžić, Miroslav and Blagojević, Duško and Popović, Ljiljana and Janićijević Hudomal, Snežana",
year = "2021",
abstract = "Supplementary Fig.S1. Scheme of the experimental design; Supplementary TableS2. Chemical analysis of commercialcold pressedpumpkin seed oil that was used in theexperiment.",
publisher = "Serbian Biological Society",
journal = "Archives of Biological Sciences",
title = "Supplementary data for the article: Radic I, Miric M, Mijovic M, Tatalovic N, Mitic M, Nestorovic V, Adzic M, Blagojevic D, Popovic L, Janicijevic-Hudomal S. Protective effects of pumpkin (Cucurbita pepo L.) seed oil on rat liver damage induced by chronic alcohol consumption. Arch Biol Sci. 2021;73(1):123–33.",
number = "1",
volume = "73",
pages = "123-133",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_4182"
}

Radić, I., Mirić, M., Mijović, M., Tatalović, N., Mitić, M., Nestorović, V., Adžić, M., Blagojević, D., Popović, L.,& Janićijević Hudomal, S.. (2021). Supplementary data for the article: Radic I, Miric M, Mijovic M, Tatalovic N, Mitic M, Nestorovic V, Adzic M, Blagojevic D, Popovic L, Janicijevic-Hudomal S. Protective effects of pumpkin (Cucurbita pepo L.) seed oil on rat liver damage induced by chronic alcohol consumption. Arch Biol Sci. 2021;73(1):123–33.. in Archives of Biological Sciences
Serbian Biological Society., 73(1), 123-133.
https://hdl.handle.net/21.15107/rcub_ibiss_4182

Radić I, Mirić M, Mijović M, Tatalović N, Mitić M, Nestorović V, Adžić M, Blagojević D, Popović L, Janićijević Hudomal S. Supplementary data for the article: Radic I, Miric M, Mijovic M, Tatalovic N, Mitic M, Nestorovic V, Adzic M, Blagojevic D, Popovic L, Janicijevic-Hudomal S. Protective effects of pumpkin (Cucurbita pepo L.) seed oil on rat liver damage induced by chronic alcohol consumption. Arch Biol Sci. 2021;73(1):123–33.. in Archives of Biological Sciences. 2021;73(1):123-133.
https://hdl.handle.net/21.15107/rcub_ibiss_4182 .

Radić, Ivan, Mirić, Mirjana, Mijović, Milica, Tatalović, Nikola, Mitić, Miloš, Nestorović, Vojkan, Adžić, Miroslav, Blagojević, Duško, Popović, Ljiljana, Janićijević Hudomal, Snežana, "Supplementary data for the article: Radic I, Miric M, Mijovic M, Tatalovic N, Mitic M, Nestorovic V, Adzic M, Blagojevic D, Popovic L, Janicijevic-Hudomal S. Protective effects of pumpkin (Cucurbita pepo L.) seed oil on rat liver damage induced by chronic alcohol consumption. Arch Biol Sci. 2021;73(1):123–33." in Archives of Biological Sciences, 73, no. 1 (2021):123-133,
https://hdl.handle.net/21.15107/rcub_ibiss_4182 .

TY  - JOUR
AU  - Radić, Ivan
AU  - Nestorović, Vojkan
AU  - Mijović, Milica
AU  - Tatalović, Nikola
AU  - Joksimović, Bojan
AU  - Lukić, Vera
AU  - Mitić, Miloš
AU  - Adžić, Miroslav
AU  - Blagojević, Duško
AU  - Veličković, Stefan
AU  - Bulajić, Sonja
AU  - Đerković, Branislav
AU  - Mirić, Mirjana
AU  - Janićijević-Hudomal, Snežana
PY  - 2018
UR  - http://www.doiserbia.nb.rs/Article.aspx?ID=0354-46641800014R
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/3282
AB  - We studied the effects of whey and pumpkin seed oil supplementation on the biochemical parameters in blood serum of male rats after chronic ad libitum alcohol consumption. The levels of AST, ALT, total bilirubin, ALP, LDH, triglycerides, total cholesterol, HDL, LDL, VLDL, triglyceride/HDL ratio, total cholesterol/HDL ratio (cholesterol ratio) and LDL/HDL ratio (index of atherosclerosis) were determined in rats after six weeks of treatment with: (i) ethanol (12% ethanol, ad libitum), (ii) whey (2 g/kg per day), (iii) pumpkin seed oil (2 mL/kg per day), (iv) both ethanol and whey, and (v) both ethanol and pumpkin seed oil. The results showed no changes in the levels of AST, ALT, total bilirubin, ALP, total cholesterol, HDL and VLDL in alcoholic rats when compared to the controls (fed with a standard laboratory diet ad libitum) and rats supplemented with whey and pumpkin seed oil. Our results suggest that alcohol consumption in small doses for 6 weeks changes lipid metabolism and significantly elevates the LDL/HDL ratio (index of atherosclerosis) but does not induce extensive liver damage. Ethanol consumption in our experimental conditions lowered the triglyceride level as well as the triglyceride/HDL ratio, suggesting lipid redistribution and the induction of some cardio-protective effect. However, ethanol induced a higher index of atherosclerosis. Pumpkin seed oil showed some protective potential in alcoholic rats by lowering the total cholesterol/HDL ratio, but it elevated the LDH. Whey consumption prevented elevation of the atherosclerosis index, pointing to its protective role, probably through the redistribution of lipids. However, whey in combination with ethanol elevated LDH.
T2  - Archives of Biological Sciences
T1  - The effects of whey and pumpkin seed oil on blood biochemical parameters of liver function and lipid profile in rats chronically drinking low concentrations of ethanol
IS  - 3
VL  - 70
DO  - 10.2298/ABS180320014R
SP  - 531
EP  - 541
ER  - 

@article{
author = "Radić, Ivan and Nestorović, Vojkan and Mijović, Milica and Tatalović, Nikola and Joksimović, Bojan and Lukić, Vera and Mitić, Miloš and Adžić, Miroslav and Blagojević, Duško and Veličković, Stefan and Bulajić, Sonja and Đerković, Branislav and Mirić, Mirjana and Janićijević-Hudomal, Snežana",
year = "2018",
abstract = "We studied the effects of whey and pumpkin seed oil supplementation on the biochemical parameters in blood serum of male rats after chronic ad libitum alcohol consumption. The levels of AST, ALT, total bilirubin, ALP, LDH, triglycerides, total cholesterol, HDL, LDL, VLDL, triglyceride/HDL ratio, total cholesterol/HDL ratio (cholesterol ratio) and LDL/HDL ratio (index of atherosclerosis) were determined in rats after six weeks of treatment with: (i) ethanol (12% ethanol, ad libitum), (ii) whey (2 g/kg per day), (iii) pumpkin seed oil (2 mL/kg per day), (iv) both ethanol and whey, and (v) both ethanol and pumpkin seed oil. The results showed no changes in the levels of AST, ALT, total bilirubin, ALP, total cholesterol, HDL and VLDL in alcoholic rats when compared to the controls (fed with a standard laboratory diet ad libitum) and rats supplemented with whey and pumpkin seed oil. Our results suggest that alcohol consumption in small doses for 6 weeks changes lipid metabolism and significantly elevates the LDL/HDL ratio (index of atherosclerosis) but does not induce extensive liver damage. Ethanol consumption in our experimental conditions lowered the triglyceride level as well as the triglyceride/HDL ratio, suggesting lipid redistribution and the induction of some cardio-protective effect. However, ethanol induced a higher index of atherosclerosis. Pumpkin seed oil showed some protective potential in alcoholic rats by lowering the total cholesterol/HDL ratio, but it elevated the LDH. Whey consumption prevented elevation of the atherosclerosis index, pointing to its protective role, probably through the redistribution of lipids. However, whey in combination with ethanol elevated LDH.",
journal = "Archives of Biological Sciences",
title = "The effects of whey and pumpkin seed oil on blood biochemical parameters of liver function and lipid profile in rats chronically drinking low concentrations of ethanol",
number = "3",
volume = "70",
doi = "10.2298/ABS180320014R",
pages = "531-541"
}

Radić, I., Nestorović, V., Mijović, M., Tatalović, N., Joksimović, B., Lukić, V., Mitić, M., Adžić, M., Blagojević, D., Veličković, S., Bulajić, S., Đerković, B., Mirić, M.,& Janićijević-Hudomal, S.. (2018). The effects of whey and pumpkin seed oil on blood biochemical parameters of liver function and lipid profile in rats chronically drinking low concentrations of ethanol. in Archives of Biological Sciences, 70(3), 531-541.
https://doi.org/10.2298/ABS180320014R

Radić I, Nestorović V, Mijović M, Tatalović N, Joksimović B, Lukić V, Mitić M, Adžić M, Blagojević D, Veličković S, Bulajić S, Đerković B, Mirić M, Janićijević-Hudomal S. The effects of whey and pumpkin seed oil on blood biochemical parameters of liver function and lipid profile in rats chronically drinking low concentrations of ethanol. in Archives of Biological Sciences. 2018;70(3):531-541.
doi:10.2298/ABS180320014R .

Radić, Ivan, Nestorović, Vojkan, Mijović, Milica, Tatalović, Nikola, Joksimović, Bojan, Lukić, Vera, Mitić, Miloš, Adžić, Miroslav, Blagojević, Duško, Veličković, Stefan, Bulajić, Sonja, Đerković, Branislav, Mirić, Mirjana, Janićijević-Hudomal, Snežana, "The effects of whey and pumpkin seed oil on blood biochemical parameters of liver function and lipid profile in rats chronically drinking low concentrations of ethanol" in Archives of Biological Sciences, 70, no. 3 (2018):531-541,
https://doi.org/10.2298/ABS180320014R . .

TY  - JOUR
AU  - Đorđević, Jelena
AU  - Đorđević, Ana
AU  - Adžić, Miroslav
AU  - Mitić, Milos
AU  - Lukić, Iva
AU  - Radojcić, Marija B
PY  - 2015
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/682
AB  - Knowledge of the antioxidant defense in the stress-responding structures of the CNS is of crucial importance, since oxidative damage is a phenomenon accompanying many stress-related disorders. Regulation of antioxidative and anti-inflammatory defense through Nrf2 (nuclear factor 2 eritroid related factor 2) pathway has emerged as a promising approach for neuroprotection. In this study, we used chronic social isolation of male Wistar rats to induce depressive-like behavior. We hypothesized that Nrf2 Keap1 pathway is compromised in the limbic brain after prolonged stress. Since subcellular trafficking of Nrf2 and its inhibitor Keap1 (Kelch ECH associating protein 1) is essential for the activation of Nrf2, we determined their protein level in cytosolic and nuclear comp& linents of hippocampus and prefrontal cortex (PEG). We also determined mRNA levels of Nr12-regulated genes involved in the production and utilization of glutathione, glutamate cysteine ligase (Gclm), glutathione S-transferase (Gsta3) and glutathione reductase (Gsr). Our results showed that chronic isolation induced anxiety and depressive-like behavior, decreased Nrf2 and in parallel increased Keap1 and nuclear factor kappa B (NF kappa B) in the hippocampus, which were not accompanied by expression profiles of Nrf2-regulated genes. Chronically stressed rats challenged with acute stress failed to induce any response of examined genes in either of brain structures, even though Nrf2/Keap1 was altered, while in naive animals Nrf2 activity corresponded witli an expression of Nrf2-regulated genes. Our results reveal maladaptive character of chronic stress at Nrf2/Keap1 level followed by pro-inflammatory conditions, and suggest a possible role of these alterations in pathogenesis of depressive/anxiety disorders. (C) 2015 Elsevier B.V. All rights reserved.
T2  - Brain Research
T1  - Alterations in the Nrf2-Keap1 signaling pathway and its downstream target genes in rat brain under stress
IS  - null
VL  - 1602
SP  - 19
EP  - 31
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_682
ER  - 

@article{
author = "Đorđević, Jelena and Đorđević, Ana and Adžić, Miroslav and Mitić, Milos and Lukić, Iva and Radojcić, Marija B",
year = "2015",
abstract = "Knowledge of the antioxidant defense in the stress-responding structures of the CNS is of crucial importance, since oxidative damage is a phenomenon accompanying many stress-related disorders. Regulation of antioxidative and anti-inflammatory defense through Nrf2 (nuclear factor 2 eritroid related factor 2) pathway has emerged as a promising approach for neuroprotection. In this study, we used chronic social isolation of male Wistar rats to induce depressive-like behavior. We hypothesized that Nrf2 Keap1 pathway is compromised in the limbic brain after prolonged stress. Since subcellular trafficking of Nrf2 and its inhibitor Keap1 (Kelch ECH associating protein 1) is essential for the activation of Nrf2, we determined their protein level in cytosolic and nuclear comp& linents of hippocampus and prefrontal cortex (PEG). We also determined mRNA levels of Nr12-regulated genes involved in the production and utilization of glutathione, glutamate cysteine ligase (Gclm), glutathione S-transferase (Gsta3) and glutathione reductase (Gsr). Our results showed that chronic isolation induced anxiety and depressive-like behavior, decreased Nrf2 and in parallel increased Keap1 and nuclear factor kappa B (NF kappa B) in the hippocampus, which were not accompanied by expression profiles of Nrf2-regulated genes. Chronically stressed rats challenged with acute stress failed to induce any response of examined genes in either of brain structures, even though Nrf2/Keap1 was altered, while in naive animals Nrf2 activity corresponded witli an expression of Nrf2-regulated genes. Our results reveal maladaptive character of chronic stress at Nrf2/Keap1 level followed by pro-inflammatory conditions, and suggest a possible role of these alterations in pathogenesis of depressive/anxiety disorders. (C) 2015 Elsevier B.V. All rights reserved.",
journal = "Brain Research",
title = "Alterations in the Nrf2-Keap1 signaling pathway and its downstream target genes in rat brain under stress",
number = "null",
volume = "1602",
pages = "19-31",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_682"
}

Đorđević, J., Đorđević, A., Adžić, M., Mitić, M., Lukić, I.,& Radojcić, M. B.. (2015). Alterations in the Nrf2-Keap1 signaling pathway and its downstream target genes in rat brain under stress. in Brain Research, 1602(null), 19-31.
https://hdl.handle.net/21.15107/rcub_ibiss_682

Đorđević J, Đorđević A, Adžić M, Mitić M, Lukić I, Radojcić MB. Alterations in the Nrf2-Keap1 signaling pathway and its downstream target genes in rat brain under stress. in Brain Research. 2015;1602(null):19-31.
https://hdl.handle.net/21.15107/rcub_ibiss_682 .

Đorđević, Jelena, Đorđević, Ana, Adžić, Miroslav, Mitić, Milos, Lukić, Iva, Radojcić, Marija B, "Alterations in the Nrf2-Keap1 signaling pathway and its downstream target genes in rat brain under stress" in Brain Research, 1602, no. null (2015):19-31,
https://hdl.handle.net/21.15107/rcub_ibiss_682 .

TY  - JOUR
AU  - Adžić, Miroslav
AU  - Lukić, Iva
AU  - Mitić, Milos Z
AU  - Đorđević, Jelena D
AU  - Elaković, Ivana
AU  - Đorđević, Ana
AU  - Krstić-Demonacos, Marija
AU  - Matić, Gordana
AU  - Radojcić, Marija B
PY  - 2013
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/940
AB  - Antidepressants affect glucocorticoid receptor (GR) functioning partly through modulation of its phosphorylation but their effects on mitochondrial GR have remained undefined. We investigated the ability of chronic fiuoxetine treatment to affect chronic stress-induced changes of mitochondrial GR and its phosphoisoforms (pGRs) in the prefrontal cortex and hippocampus of female and male rats. Since mitochondrial GR regulates oxidative phosphorylation, expression of mitochondrial-encoded subunits of cytochrome (cyt) c oxidase and its activity were also investigated. Chronic stress caused accumulation of the GR in mitochondria of female prefrontal cortex, while the changes in the hippocampus were sex-specific at the levels of pGRs. Expression of mitochondrial COXs genes corresponded to chronic stress-modulated mitochondrial GR in both tissues of both genders and to cyt c oxidase activity in females. Moreover, the metabolic parameters in stressed animals were affected by fiuoxetine therapy only in the hippocampus. Namely, fluoxetine effects on mitochondrial COXs and cyt c oxidase activity in the hippocampus seem to be conveyed through pGR232 in females, while in males this likely occurs through other mechanisms. In summary, sex-specific regulation of cyt c oxidase by the stress and antidepressant treatment and its differential convergence with mitochondrial GR signaling in the prefrontal cortex and hippocampus could contribute to clarification of sex-dependent vulnerability to stress-related disorders and sex-specific clinical impact of antidepressants. (C) 2013 Elsevier Ltd. All rights reserved.
T2  - Psychoneuroendocrinology
T1  - Brain region- and sex-specific modulation of mitochondrial glucocorticoid receptor phosphorylation in fluoxetine treated stressed rats: Effects on energy metabolism
IS  - 12
VL  - 38
SP  - 1459
EP  - 2924
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_940
ER  - 

@article{
author = "Adžić, Miroslav and Lukić, Iva and Mitić, Milos Z and Đorđević, Jelena D and Elaković, Ivana and Đorđević, Ana and Krstić-Demonacos, Marija and Matić, Gordana and Radojcić, Marija B",
year = "2013",
abstract = "Antidepressants affect glucocorticoid receptor (GR) functioning partly through modulation of its phosphorylation but their effects on mitochondrial GR have remained undefined. We investigated the ability of chronic fiuoxetine treatment to affect chronic stress-induced changes of mitochondrial GR and its phosphoisoforms (pGRs) in the prefrontal cortex and hippocampus of female and male rats. Since mitochondrial GR regulates oxidative phosphorylation, expression of mitochondrial-encoded subunits of cytochrome (cyt) c oxidase and its activity were also investigated. Chronic stress caused accumulation of the GR in mitochondria of female prefrontal cortex, while the changes in the hippocampus were sex-specific at the levels of pGRs. Expression of mitochondrial COXs genes corresponded to chronic stress-modulated mitochondrial GR in both tissues of both genders and to cyt c oxidase activity in females. Moreover, the metabolic parameters in stressed animals were affected by fiuoxetine therapy only in the hippocampus. Namely, fluoxetine effects on mitochondrial COXs and cyt c oxidase activity in the hippocampus seem to be conveyed through pGR232 in females, while in males this likely occurs through other mechanisms. In summary, sex-specific regulation of cyt c oxidase by the stress and antidepressant treatment and its differential convergence with mitochondrial GR signaling in the prefrontal cortex and hippocampus could contribute to clarification of sex-dependent vulnerability to stress-related disorders and sex-specific clinical impact of antidepressants. (C) 2013 Elsevier Ltd. All rights reserved.",
journal = "Psychoneuroendocrinology",
title = "Brain region- and sex-specific modulation of mitochondrial glucocorticoid receptor phosphorylation in fluoxetine treated stressed rats: Effects on energy metabolism",
number = "12",
volume = "38",
pages = "1459-2924",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_940"
}

Adžić, M., Lukić, I., Mitić, M. Z., Đorđević, J. D., Elaković, I., Đorđević, A., Krstić-Demonacos, M., Matić, G.,& Radojcić, M. B.. (2013). Brain region- and sex-specific modulation of mitochondrial glucocorticoid receptor phosphorylation in fluoxetine treated stressed rats: Effects on energy metabolism. in Psychoneuroendocrinology, 38(12), 1459-2924.
https://hdl.handle.net/21.15107/rcub_ibiss_940

Adžić M, Lukić I, Mitić MZ, Đorđević JD, Elaković I, Đorđević A, Krstić-Demonacos M, Matić G, Radojcić MB. Brain region- and sex-specific modulation of mitochondrial glucocorticoid receptor phosphorylation in fluoxetine treated stressed rats: Effects on energy metabolism. in Psychoneuroendocrinology. 2013;38(12):1459-2924.
https://hdl.handle.net/21.15107/rcub_ibiss_940 .

Adžić, Miroslav, Lukić, Iva, Mitić, Milos Z, Đorđević, Jelena D, Elaković, Ivana, Đorđević, Ana, Krstić-Demonacos, Marija, Matić, Gordana, Radojcić, Marija B, "Brain region- and sex-specific modulation of mitochondrial glucocorticoid receptor phosphorylation in fluoxetine treated stressed rats: Effects on energy metabolism" in Psychoneuroendocrinology, 38, no. 12 (2013):1459-2924,
https://hdl.handle.net/21.15107/rcub_ibiss_940 .

TY  - JOUR
AU  - Đorđević, Ana
AU  - Đorđević, Jelena D
AU  - Elaković, Ivana
AU  - Adžić, Miroslav
AU  - Matić, Gordana
AU  - Radojcić, Marija B
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1211
AB  - Plastic response and successful adaptation to stress are of particular importance in the hippocampus, where chronic stress may cause cell death instead of neural remodeling. Structural modifications that occur both in the brain of depressed patients and animal stress models may be reversed by antidepressants. Since morphological changes induced by stress and/or antidepressants could be mediated by presynaptically located proteins, determining the levels of these proteins may be a useful way to identify molecular changes associated with synaptic plasticity. In this study we analyzed the effects of chronic (six-week) social isolation and long-term (three-week) fluoxetine treatment on molecular markers of plasticity and apoptosis in the hippocampus of Wistar rats. Compartmental redistribution of NF kappa B transcription factor involved in the regulation of plasticity and apoptosis was also examined. To establish whether social isolation is able to evoke behavioral-like effects, which might be related to the observed molecular changes, we performed the forced swimming test. The results show that synaptosomal polysialic neural cell adhesion molecule (PSA-NCAM), a molecular plasticity marker, was increased in the hippocampus of chronically isolated rats, while subsequent treatment with fluoxetine set it at the control level. In addition, analysis of cytoplasm/mitochondria redistribution of apoptotic proteins Bax and Bcl-2 after exposure to chronic isolation stress, revealed an increase in Bcl-2 protein expression in both compartments, while fluoxetine enhanced the effect of stress only in the mitochondria. The observed alterations at the molecular level were accompanied by normalization of stress-induced behavioral changes by fluoxetine. (C) 2011 Elsevier Inc. All rights reserved.
T2  - Progress in Neuro-Psychopharmacology & Biological Psychiatry
T1  - Fluoxetine affects hippocampal plasticity, apoptosis and depressive-like behavior of chronically isolated rats
IS  - 1
VL  - 36
EP  - 100
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1211
ER  - 

@article{
author = "Đorđević, Ana and Đorđević, Jelena D and Elaković, Ivana and Adžić, Miroslav and Matić, Gordana and Radojcić, Marija B",
year = "2012",
abstract = "Plastic response and successful adaptation to stress are of particular importance in the hippocampus, where chronic stress may cause cell death instead of neural remodeling. Structural modifications that occur both in the brain of depressed patients and animal stress models may be reversed by antidepressants. Since morphological changes induced by stress and/or antidepressants could be mediated by presynaptically located proteins, determining the levels of these proteins may be a useful way to identify molecular changes associated with synaptic plasticity. In this study we analyzed the effects of chronic (six-week) social isolation and long-term (three-week) fluoxetine treatment on molecular markers of plasticity and apoptosis in the hippocampus of Wistar rats. Compartmental redistribution of NF kappa B transcription factor involved in the regulation of plasticity and apoptosis was also examined. To establish whether social isolation is able to evoke behavioral-like effects, which might be related to the observed molecular changes, we performed the forced swimming test. The results show that synaptosomal polysialic neural cell adhesion molecule (PSA-NCAM), a molecular plasticity marker, was increased in the hippocampus of chronically isolated rats, while subsequent treatment with fluoxetine set it at the control level. In addition, analysis of cytoplasm/mitochondria redistribution of apoptotic proteins Bax and Bcl-2 after exposure to chronic isolation stress, revealed an increase in Bcl-2 protein expression in both compartments, while fluoxetine enhanced the effect of stress only in the mitochondria. The observed alterations at the molecular level were accompanied by normalization of stress-induced behavioral changes by fluoxetine. (C) 2011 Elsevier Inc. All rights reserved.",
journal = "Progress in Neuro-Psychopharmacology & Biological Psychiatry",
title = "Fluoxetine affects hippocampal plasticity, apoptosis and depressive-like behavior of chronically isolated rats",
number = "1",
volume = "36",
pages = "100",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1211"
}

Đorđević, A., Đorđević, J. D., Elaković, I., Adžić, M., Matić, G.,& Radojcić, M. B.. (2012). Fluoxetine affects hippocampal plasticity, apoptosis and depressive-like behavior of chronically isolated rats. in Progress in Neuro-Psychopharmacology & Biological Psychiatry, 36(1).
https://hdl.handle.net/21.15107/rcub_ibiss_1211

Đorđević A, Đorđević JD, Elaković I, Adžić M, Matić G, Radojcić MB. Fluoxetine affects hippocampal plasticity, apoptosis and depressive-like behavior of chronically isolated rats. in Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2012;36(1):null-100.
https://hdl.handle.net/21.15107/rcub_ibiss_1211 .

Đorđević, Ana, Đorđević, Jelena D, Elaković, Ivana, Adžić, Miroslav, Matić, Gordana, Radojcić, Marija B, "Fluoxetine affects hippocampal plasticity, apoptosis and depressive-like behavior of chronically isolated rats" in Progress in Neuro-Psychopharmacology & Biological Psychiatry, 36, no. 1 (2012),
https://hdl.handle.net/21.15107/rcub_ibiss_1211 .

TY  - JOUR
AU  - Đorđević, Ana
AU  - Đorđević, Jelena D
AU  - Elaković, Ivana
AU  - Adžić, Miroslav
AU  - Matić, Gordana
AU  - Radojcić, Marija B
PY  - 2012
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1094
AB  - The prefrontal cortex is the brain region sensitive to detrimental effects of stress and even mild stress can rapidly impair its function. Aside from initiating proadaptive neuroplastic changes in the prefrontal cortex, chronic stress may also increase vulnerability of cortical neurons to apoptosis. Understanding the mechanism of plasticity and apoptotic processes is of immense importance for therapy of stress-related psychiatric disorders. In this study we tested whether molecular alterations in the prefrontal cortex, which occurred upon chronic social isolation, could be influenced by a prolonged fluoxetine treatment. We analyzed the expression of synaptic plasticity and apoptotic molecular markers in the prefrontal cortex of young-adult male Wistar rats exposed to 6-week social isolation with and without fluoxetine treatment during the last 3 weeks. Compartmental redistribution of NF kappa B transcription factor, involved in regulation of plasticity and apoptosis, was also examined. The level of synaptosomal polysialic neural cell adhesion molecule(PSA-NCAM) was increased in the prefrontal cortex of isolated rats as compared to untreated controls. Treatment with fluoxetine reduced the PSA-NCAM level only in isolated animals. In addition, mitochondrial Bax protein was elevated by chronic social isolation, while fluoxetine failed to abolish this effect. Inspite of elevated Bcl-2 in the mitochondria, the calculated Bax/Bcl-2 ratio and concomitant absence of NF kappa B activation pointed to initiation of apoptotic signaling in the prefrontal cortex. The result simply that fluoxetine influences plasticity in the prefrontal cortex of chronically isolated rats and fails to prevent stress-induced initiation of apoptosis in this brain structure. (c) 2012 Elsevier B.V. All rights reserved.
T2  - European Journal of Pharmacology
T1  - Effects of fluoxetine on plasticity and apoptosis evoked by chronic stress in rat prefrontal cortex
IS  - 1-3
VL  - 693
SP  - 375
EP  - 44
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1094
ER  - 

@article{
author = "Đorđević, Ana and Đorđević, Jelena D and Elaković, Ivana and Adžić, Miroslav and Matić, Gordana and Radojcić, Marija B",
year = "2012",
abstract = "The prefrontal cortex is the brain region sensitive to detrimental effects of stress and even mild stress can rapidly impair its function. Aside from initiating proadaptive neuroplastic changes in the prefrontal cortex, chronic stress may also increase vulnerability of cortical neurons to apoptosis. Understanding the mechanism of plasticity and apoptotic processes is of immense importance for therapy of stress-related psychiatric disorders. In this study we tested whether molecular alterations in the prefrontal cortex, which occurred upon chronic social isolation, could be influenced by a prolonged fluoxetine treatment. We analyzed the expression of synaptic plasticity and apoptotic molecular markers in the prefrontal cortex of young-adult male Wistar rats exposed to 6-week social isolation with and without fluoxetine treatment during the last 3 weeks. Compartmental redistribution of NF kappa B transcription factor, involved in regulation of plasticity and apoptosis, was also examined. The level of synaptosomal polysialic neural cell adhesion molecule(PSA-NCAM) was increased in the prefrontal cortex of isolated rats as compared to untreated controls. Treatment with fluoxetine reduced the PSA-NCAM level only in isolated animals. In addition, mitochondrial Bax protein was elevated by chronic social isolation, while fluoxetine failed to abolish this effect. Inspite of elevated Bcl-2 in the mitochondria, the calculated Bax/Bcl-2 ratio and concomitant absence of NF kappa B activation pointed to initiation of apoptotic signaling in the prefrontal cortex. The result simply that fluoxetine influences plasticity in the prefrontal cortex of chronically isolated rats and fails to prevent stress-induced initiation of apoptosis in this brain structure. (c) 2012 Elsevier B.V. All rights reserved.",
journal = "European Journal of Pharmacology",
title = "Effects of fluoxetine on plasticity and apoptosis evoked by chronic stress in rat prefrontal cortex",
number = "1-3",
volume = "693",
pages = "375-44",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1094"
}

Đorđević, A., Đorđević, J. D., Elaković, I., Adžić, M., Matić, G.,& Radojcić, M. B.. (2012). Effects of fluoxetine on plasticity and apoptosis evoked by chronic stress in rat prefrontal cortex. in European Journal of Pharmacology, 693(1-3), 375-44.
https://hdl.handle.net/21.15107/rcub_ibiss_1094

Đorđević A, Đorđević JD, Elaković I, Adžić M, Matić G, Radojcić MB. Effects of fluoxetine on plasticity and apoptosis evoked by chronic stress in rat prefrontal cortex. in European Journal of Pharmacology. 2012;693(1-3):375-44.
https://hdl.handle.net/21.15107/rcub_ibiss_1094 .

Đorđević, Ana, Đorđević, Jelena D, Elaković, Ivana, Adžić, Miroslav, Matić, Gordana, Radojcić, Marija B, "Effects of fluoxetine on plasticity and apoptosis evoked by chronic stress in rat prefrontal cortex" in European Journal of Pharmacology, 693, no. 1-3 (2012):375-44,
https://hdl.handle.net/21.15107/rcub_ibiss_1094 .

TY  - JOUR
AU  - Adžić, Miroslav
AU  - Đorđević, Jelena D
AU  - Mitić, Milos Z
AU  - Simić, Iva
AU  - Rackov, Gorjana
AU  - Đorđević, Ana
AU  - Elaković, Ivana
AU  - Matić, Gordana
AU  - Radojcić, Marija B
PY  - 2011
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1319
AB  - Alterations in the antioxidative defense parameters upon chronic stress are considered critical for pathophysiology of stress related psychiatric disorders, and their status in blood serves as biomarker for effects of pharmacological treatments. The present study was designed to investigate the modulation of erythrocyte antioxidant enzymes (AOEs): CuZn superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GLR) activities and their protein expression in Wistar male rats subjected to chronic psychosocial isolation and/or to pharmacological treatment with fluoxetine. Chronically isolated animals exhibited decreased levels of serum corticosterone, as opposed to other chronic stress paradigms. In addition to that, SOD, CAT and GPx status was not altered either by chronic psychosocial isolation or by fluoxetine treatment. In contrast, GLR activity and its protein level were both markedly reduced by fluoxetine. Since, GLR is crucial for overall oxido-reductive balance through maintaining optimal ratio of reduced/oxidized glutathione level (GSH/GSSG) in erythrocytes, these results could indicate that in spite of numerous beneficial effects of fluoxetine, it may compromise both haemoglobin function and oxygen transport.
T2  - Acta Chimica Slovenica
T1  - Fluoxetine Decreases Glutathione Reductase in Erythrocytes of Chronically Isolated Wistar Rats
IS  - 4
VL  - 58
EP  - 791
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1319
ER  - 

@article{
author = "Adžić, Miroslav and Đorđević, Jelena D and Mitić, Milos Z and Simić, Iva and Rackov, Gorjana and Đorđević, Ana and Elaković, Ivana and Matić, Gordana and Radojcić, Marija B",
year = "2011",
abstract = "Alterations in the antioxidative defense parameters upon chronic stress are considered critical for pathophysiology of stress related psychiatric disorders, and their status in blood serves as biomarker for effects of pharmacological treatments. The present study was designed to investigate the modulation of erythrocyte antioxidant enzymes (AOEs): CuZn superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GLR) activities and their protein expression in Wistar male rats subjected to chronic psychosocial isolation and/or to pharmacological treatment with fluoxetine. Chronically isolated animals exhibited decreased levels of serum corticosterone, as opposed to other chronic stress paradigms. In addition to that, SOD, CAT and GPx status was not altered either by chronic psychosocial isolation or by fluoxetine treatment. In contrast, GLR activity and its protein level were both markedly reduced by fluoxetine. Since, GLR is crucial for overall oxido-reductive balance through maintaining optimal ratio of reduced/oxidized glutathione level (GSH/GSSG) in erythrocytes, these results could indicate that in spite of numerous beneficial effects of fluoxetine, it may compromise both haemoglobin function and oxygen transport.",
journal = "Acta Chimica Slovenica",
title = "Fluoxetine Decreases Glutathione Reductase in Erythrocytes of Chronically Isolated Wistar Rats",
number = "4",
volume = "58",
pages = "791",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1319"
}

Adžić, M., Đorđević, J. D., Mitić, M. Z., Simić, I., Rackov, G., Đorđević, A., Elaković, I., Matić, G.,& Radojcić, M. B.. (2011). Fluoxetine Decreases Glutathione Reductase in Erythrocytes of Chronically Isolated Wistar Rats. in Acta Chimica Slovenica, 58(4).
https://hdl.handle.net/21.15107/rcub_ibiss_1319

Adžić M, Đorđević JD, Mitić MZ, Simić I, Rackov G, Đorđević A, Elaković I, Matić G, Radojcić MB. Fluoxetine Decreases Glutathione Reductase in Erythrocytes of Chronically Isolated Wistar Rats. in Acta Chimica Slovenica. 2011;58(4):null-791.
https://hdl.handle.net/21.15107/rcub_ibiss_1319 .

Adžić, Miroslav, Đorđević, Jelena D, Mitić, Milos Z, Simić, Iva, Rackov, Gorjana, Đorđević, Ana, Elaković, Ivana, Matić, Gordana, Radojcić, Marija B, "Fluoxetine Decreases Glutathione Reductase in Erythrocytes of Chronically Isolated Wistar Rats" in Acta Chimica Slovenica, 58, no. 4 (2011),
https://hdl.handle.net/21.15107/rcub_ibiss_1319 .

TY  - JOUR
AU  - Elaković, Ivana
AU  - Đorđević, Ana
AU  - Adžić, Miroslav
AU  - Đorđević, Jelena D
AU  - Radojcić, Marija B
AU  - Matić, Gordana
PY  - 2011
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1298
AB  - Gender-related differences in dexamethasone binding to corticosteroid receptors (CR) and in glucocorticoid receptor (GR) protein level in the pituitary, hypothalamus, hippocampus and prefrontal cortex were studied before and after antidepressant fluoxetine administration to both unstressed and rats exposed to a chronic social isolation stress. Untreated males, in comparison to females, displayed higher hormone-binding capacity of both GR and mineralocorticoid receptor (MR) in the hippocampal cytosol, as well as higher GR protein level in the pituitary cytosol. In both genders, dexamethasone binding to MR exceeded that to GR. While fluoxetine treatment and social isolation had no effect on GR activity, the influence on MR was gender-specific. Fluoxetine facilitated MR hormone-binding only in females, increasing the MR/GA activity ratio. In contrast, after a 6-week isolation of males, MR binding capacity was diminished and MR/GR ratio inverted in favor of GR In addition, fluoxetine induced elevation of cytosolic GR protein level in the pituitary and hypothalamus, the latter change being gender-specific. The results point to gender-related differences in the CRs functioning and suggest that both MR and GR may contribute to well-known sexual dimorphism in vulnerability to stress and stress-related disorders and in the outcome of antidepressant treatment. (C) 2011 Elsevier B.V. All rights reserved.
T2  - Brain Research
T1  - Gender-specific response of brain corticosteroid receptors to stress and fluoxetine
IS  - null
VL  - 1384
EP  - 68
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1298
ER  - 

@article{
author = "Elaković, Ivana and Đorđević, Ana and Adžić, Miroslav and Đorđević, Jelena D and Radojcić, Marija B and Matić, Gordana",
year = "2011",
abstract = "Gender-related differences in dexamethasone binding to corticosteroid receptors (CR) and in glucocorticoid receptor (GR) protein level in the pituitary, hypothalamus, hippocampus and prefrontal cortex were studied before and after antidepressant fluoxetine administration to both unstressed and rats exposed to a chronic social isolation stress. Untreated males, in comparison to females, displayed higher hormone-binding capacity of both GR and mineralocorticoid receptor (MR) in the hippocampal cytosol, as well as higher GR protein level in the pituitary cytosol. In both genders, dexamethasone binding to MR exceeded that to GR. While fluoxetine treatment and social isolation had no effect on GR activity, the influence on MR was gender-specific. Fluoxetine facilitated MR hormone-binding only in females, increasing the MR/GA activity ratio. In contrast, after a 6-week isolation of males, MR binding capacity was diminished and MR/GR ratio inverted in favor of GR In addition, fluoxetine induced elevation of cytosolic GR protein level in the pituitary and hypothalamus, the latter change being gender-specific. The results point to gender-related differences in the CRs functioning and suggest that both MR and GR may contribute to well-known sexual dimorphism in vulnerability to stress and stress-related disorders and in the outcome of antidepressant treatment. (C) 2011 Elsevier B.V. All rights reserved.",
journal = "Brain Research",
title = "Gender-specific response of brain corticosteroid receptors to stress and fluoxetine",
number = "null",
volume = "1384",
pages = "68",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1298"
}

Elaković, I., Đorđević, A., Adžić, M., Đorđević, J. D., Radojcić, M. B.,& Matić, G.. (2011). Gender-specific response of brain corticosteroid receptors to stress and fluoxetine. in Brain Research, 1384(null).
https://hdl.handle.net/21.15107/rcub_ibiss_1298

Elaković I, Đorđević A, Adžić M, Đorđević JD, Radojcić MB, Matić G. Gender-specific response of brain corticosteroid receptors to stress and fluoxetine. in Brain Research. 2011;1384(null):null-68.
https://hdl.handle.net/21.15107/rcub_ibiss_1298 .

Elaković, Ivana, Đorđević, Ana, Adžić, Miroslav, Đorđević, Jelena D, Radojcić, Marija B, Matić, Gordana, "Gender-specific response of brain corticosteroid receptors to stress and fluoxetine" in Brain Research, 1384, no. null (2011),
https://hdl.handle.net/21.15107/rcub_ibiss_1298 .

TY  - JOUR
AU  - Đorđević, Jelena D
AU  - Đorđević, Ana
AU  - Adžić, Miroslav
AU  - Elaković, Ivana
AU  - Matić, Gordana
AU  - Radojcić, Marija B
PY  - 2011
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1290
AB  - Selective serotonin reuptake inhibitors (SSRI) are a treatment of choice for stress related disorders including clinical depression and a range of anxiety-related disorders. In the experimental animals, chronic stress paradigms are considered as a model of depression, and in that context are used for examining the effects of different drug treatments. The present research was designed to investigate the effect of SSRI fluoxetine on antioxidant status and apoptotic signaling in Wistar rat liver, which is a central organ for activation and detoxification of many xenobiotics and reactive oxygen species. We also investigated whether chronic fluoxetine treatment exhibits the same effects in the liver of control animals vs. animals stressed by chronic psychosocial isolation. Our results revealed that fluoxetine downregulated the activity of superoxide dismutases and upregulated the activity of glutathione peroxidase in both rat groups, while elevating glutathione reductase activity and total antioxidant status only in stressed animals. These results suggested that fluoxetine interfered with stress-induced pathways of oxidative defense in the liver. In addition, in both experimental groups, fluoxetine induced several hallmarks of apoptosis in the liver, including a decrease in Bcl-2 expression and increased DNA fragmentation. However, apoptotic alterations were more pronounced in stressed animals, suggesting that stress related oxidative damage could have primed apoptotic effects of fluoxetine. (C) 2011 Elsevier B.V. All rights reserved.
T2  - European Journal of Pharmacology
T1  - Fluoxetine affects antioxidant system and promotes apoptotic signaling in Wistar rat liver
IS  - 1
VL  - 659
EP  - 66
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1290
ER  - 

@article{
author = "Đorđević, Jelena D and Đorđević, Ana and Adžić, Miroslav and Elaković, Ivana and Matić, Gordana and Radojcić, Marija B",
year = "2011",
abstract = "Selective serotonin reuptake inhibitors (SSRI) are a treatment of choice for stress related disorders including clinical depression and a range of anxiety-related disorders. In the experimental animals, chronic stress paradigms are considered as a model of depression, and in that context are used for examining the effects of different drug treatments. The present research was designed to investigate the effect of SSRI fluoxetine on antioxidant status and apoptotic signaling in Wistar rat liver, which is a central organ for activation and detoxification of many xenobiotics and reactive oxygen species. We also investigated whether chronic fluoxetine treatment exhibits the same effects in the liver of control animals vs. animals stressed by chronic psychosocial isolation. Our results revealed that fluoxetine downregulated the activity of superoxide dismutases and upregulated the activity of glutathione peroxidase in both rat groups, while elevating glutathione reductase activity and total antioxidant status only in stressed animals. These results suggested that fluoxetine interfered with stress-induced pathways of oxidative defense in the liver. In addition, in both experimental groups, fluoxetine induced several hallmarks of apoptosis in the liver, including a decrease in Bcl-2 expression and increased DNA fragmentation. However, apoptotic alterations were more pronounced in stressed animals, suggesting that stress related oxidative damage could have primed apoptotic effects of fluoxetine. (C) 2011 Elsevier B.V. All rights reserved.",
journal = "European Journal of Pharmacology",
title = "Fluoxetine affects antioxidant system and promotes apoptotic signaling in Wistar rat liver",
number = "1",
volume = "659",
pages = "66",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1290"
}

Đorđević, J. D., Đorđević, A., Adžić, M., Elaković, I., Matić, G.,& Radojcić, M. B.. (2011). Fluoxetine affects antioxidant system and promotes apoptotic signaling in Wistar rat liver. in European Journal of Pharmacology, 659(1).
https://hdl.handle.net/21.15107/rcub_ibiss_1290

Đorđević JD, Đorđević A, Adžić M, Elaković I, Matić G, Radojcić MB. Fluoxetine affects antioxidant system and promotes apoptotic signaling in Wistar rat liver. in European Journal of Pharmacology. 2011;659(1):null-66.
https://hdl.handle.net/21.15107/rcub_ibiss_1290 .

Đorđević, Jelena D, Đorđević, Ana, Adžić, Miroslav, Elaković, Ivana, Matić, Gordana, Radojcić, Marija B, "Fluoxetine affects antioxidant system and promotes apoptotic signaling in Wistar rat liver" in European Journal of Pharmacology, 659, no. 1 (2011),
https://hdl.handle.net/21.15107/rcub_ibiss_1290 .

TY  - JOUR
AU  - Matić, Gordana
AU  - Elaković, Ivana
AU  - Vasiljević, Đorđe
AU  - Adžić, Miroslav
AU  - Đorđević, Ana
AU  - Đorđević, Jelena D
AU  - Radojcić, Marija B
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1385
AB  - Gender-related differences in the expression and functional properties of the hepatic glucocorticoid receptor were studied before and after antidepressant fluoxetine administration to both unstressed and rats exposed to a chronic social isolation stress. Some of the receptor's functional properties, including hormone-binding capacity (B(max)), hormone-binding potency (B(max)/K(D) ratio) and the DNA-binding ability, were found to be sexually dimorphic. Fluoxetine treatment (5 mg/kg body mass, 21 day, intraperitoneally) induced a decrease in B(max) and in the amount of Hsp70 co-immunoprecipitated with the glucocorticoid receptor only in males, and stimulated the association of the receptor with Hsp90 in females. When applied during the last three weeks of the 6-week isolation, fluoxetine parallelly elevated B(max) and the receptor protein level in female animals, while in males diminished B(max) and inhibited association of the receptor with Hsp70. Binding of dexamethasone-receptor complexes both to DNA-cellulose and to isolated liver nuclei did not appear to be a target for fluoxetine action. The results point to sex-related differences in the glucocorticoid receptor functioning and in its response to fluoxetine, and suggest that these differences may contribute to well known sexual dimorphism in the sensitivity to stress, to stress-related disorders and to antidepressant treatment. (C) 2010 Elsevier B.V. All rights reserved.
T2  - European Journal of Pharmacology
T1  - Sexually dimorphic functional alterations of rat hepatic glucocorticoid receptor in response to fluoxetine
IS  - 1-3
VL  - 632
EP  - 85
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1385
ER  - 

@article{
author = "Matić, Gordana and Elaković, Ivana and Vasiljević, Đorđe and Adžić, Miroslav and Đorđević, Ana and Đorđević, Jelena D and Radojcić, Marija B",
year = "2010",
abstract = "Gender-related differences in the expression and functional properties of the hepatic glucocorticoid receptor were studied before and after antidepressant fluoxetine administration to both unstressed and rats exposed to a chronic social isolation stress. Some of the receptor's functional properties, including hormone-binding capacity (B(max)), hormone-binding potency (B(max)/K(D) ratio) and the DNA-binding ability, were found to be sexually dimorphic. Fluoxetine treatment (5 mg/kg body mass, 21 day, intraperitoneally) induced a decrease in B(max) and in the amount of Hsp70 co-immunoprecipitated with the glucocorticoid receptor only in males, and stimulated the association of the receptor with Hsp90 in females. When applied during the last three weeks of the 6-week isolation, fluoxetine parallelly elevated B(max) and the receptor protein level in female animals, while in males diminished B(max) and inhibited association of the receptor with Hsp70. Binding of dexamethasone-receptor complexes both to DNA-cellulose and to isolated liver nuclei did not appear to be a target for fluoxetine action. The results point to sex-related differences in the glucocorticoid receptor functioning and in its response to fluoxetine, and suggest that these differences may contribute to well known sexual dimorphism in the sensitivity to stress, to stress-related disorders and to antidepressant treatment. (C) 2010 Elsevier B.V. All rights reserved.",
journal = "European Journal of Pharmacology",
title = "Sexually dimorphic functional alterations of rat hepatic glucocorticoid receptor in response to fluoxetine",
number = "1-3",
volume = "632",
pages = "85",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1385"
}

Matić, G., Elaković, I., Vasiljević, Đ., Adžić, M., Đorđević, A., Đorđević, J. D.,& Radojcić, M. B.. (2010). Sexually dimorphic functional alterations of rat hepatic glucocorticoid receptor in response to fluoxetine. in European Journal of Pharmacology, 632(1-3).
https://hdl.handle.net/21.15107/rcub_ibiss_1385

Matić G, Elaković I, Vasiljević Đ, Adžić M, Đorđević A, Đorđević JD, Radojcić MB. Sexually dimorphic functional alterations of rat hepatic glucocorticoid receptor in response to fluoxetine. in European Journal of Pharmacology. 2010;632(1-3):null-85.
https://hdl.handle.net/21.15107/rcub_ibiss_1385 .

Matić, Gordana, Elaković, Ivana, Vasiljević, Đorđe, Adžić, Miroslav, Đorđević, Ana, Đorđević, Jelena D, Radojcić, Marija B, "Sexually dimorphic functional alterations of rat hepatic glucocorticoid receptor in response to fluoxetine" in European Journal of Pharmacology, 632, no. 1-3 (2010),
https://hdl.handle.net/21.15107/rcub_ibiss_1385 .

TY  - JOUR
AU  - Popović, Natasa M
AU  - Ruždijić, Sabera
AU  - Kanazir, Dusan T.
AU  - Niciforović, Ana
AU  - Adžić, Miroslav
AU  - Paraskevopoulou, Elissavet
AU  - Pantelidou, Constantia
AU  - Radojcić, Marija B
AU  - Demonacos, Constantinos
AU  - Krstić-Demonacos, Marija
PY  - 2010
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1375
AB  - The glucocorticoid receptor (GR) signal transduction and transcriptional regulation are efficiently recapitulated when GR is expressed in Saccharomyces cerevisiae. In this report we demonstrate that the in vivo GR phosphorylation pattern, hormone dependency and interdependency of phosphorylation events were similar in yeast and mammalian cells. GR phosphorylation at S246 exhibited inhibitory effect on S224 and S232 phosphorylation, suggesting the conservation of molecular mechanisms that control this interdependence between yeast and mammalian cells. To assess the effects of GR phosphorylation the mutated GR derivatives T171A, S224A, S232A, S246A were overexpressed and their transcriptional activity was analysed. These receptor derivatives displayed significant hormone inducible transcription when overexpressed in S. cerevisiae. We have established an inducible methionine expression system, which allows the close regulation of the receptor protein levels to analyse the dependence of GR function on its phosphorylation and protein abundance. Using this system we observed that GR S246A mutation increased its activity across all of the GR concentrations tested. The activity of the S224A and S246A mutants was mostly independent of GR protein levels, whereas the WT, T171A and S232A mediated transcription diminished with declining GR protein levels. Our results suggest that GR phosphorylation at specific residues affects its transcriptional functions in a site selective manner and these effects were directly linked to GR dosage. Crown Copyright (C) 2010 Published by Elsevier Inc. All rights reserved.
T2  - Steroids
T1  - Site-specific and dose-dependent effects of glucocorticoid receptor phosphorylation in yeast Saccharomyces cerevisiae
IS  - 6
VL  - 75
EP  - 465
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1375
ER  - 

@article{
author = "Popović, Natasa M and Ruždijić, Sabera and Kanazir, Dusan T. and Niciforović, Ana and Adžić, Miroslav and Paraskevopoulou, Elissavet and Pantelidou, Constantia and Radojcić, Marija B and Demonacos, Constantinos and Krstić-Demonacos, Marija",
year = "2010",
abstract = "The glucocorticoid receptor (GR) signal transduction and transcriptional regulation are efficiently recapitulated when GR is expressed in Saccharomyces cerevisiae. In this report we demonstrate that the in vivo GR phosphorylation pattern, hormone dependency and interdependency of phosphorylation events were similar in yeast and mammalian cells. GR phosphorylation at S246 exhibited inhibitory effect on S224 and S232 phosphorylation, suggesting the conservation of molecular mechanisms that control this interdependence between yeast and mammalian cells. To assess the effects of GR phosphorylation the mutated GR derivatives T171A, S224A, S232A, S246A were overexpressed and their transcriptional activity was analysed. These receptor derivatives displayed significant hormone inducible transcription when overexpressed in S. cerevisiae. We have established an inducible methionine expression system, which allows the close regulation of the receptor protein levels to analyse the dependence of GR function on its phosphorylation and protein abundance. Using this system we observed that GR S246A mutation increased its activity across all of the GR concentrations tested. The activity of the S224A and S246A mutants was mostly independent of GR protein levels, whereas the WT, T171A and S232A mediated transcription diminished with declining GR protein levels. Our results suggest that GR phosphorylation at specific residues affects its transcriptional functions in a site selective manner and these effects were directly linked to GR dosage. Crown Copyright (C) 2010 Published by Elsevier Inc. All rights reserved.",
journal = "Steroids",
title = "Site-specific and dose-dependent effects of glucocorticoid receptor phosphorylation in yeast Saccharomyces cerevisiae",
number = "6",
volume = "75",
pages = "465",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1375"
}

Popović, N. M., Ruždijić, S., Kanazir, D. T., Niciforović, A., Adžić, M., Paraskevopoulou, E., Pantelidou, C., Radojcić, M. B., Demonacos, C.,& Krstić-Demonacos, M.. (2010). Site-specific and dose-dependent effects of glucocorticoid receptor phosphorylation in yeast Saccharomyces cerevisiae. in Steroids, 75(6).
https://hdl.handle.net/21.15107/rcub_ibiss_1375

Popović NM, Ruždijić S, Kanazir DT, Niciforović A, Adžić M, Paraskevopoulou E, Pantelidou C, Radojcić MB, Demonacos C, Krstić-Demonacos M. Site-specific and dose-dependent effects of glucocorticoid receptor phosphorylation in yeast Saccharomyces cerevisiae. in Steroids. 2010;75(6):null-465.
https://hdl.handle.net/21.15107/rcub_ibiss_1375 .

Popović, Natasa M, Ruždijić, Sabera, Kanazir, Dusan T., Niciforović, Ana, Adžić, Miroslav, Paraskevopoulou, Elissavet, Pantelidou, Constantia, Radojcić, Marija B, Demonacos, Constantinos, Krstić-Demonacos, Marija, "Site-specific and dose-dependent effects of glucocorticoid receptor phosphorylation in yeast Saccharomyces cerevisiae" in Steroids, 75, no. 6 (2010),
https://hdl.handle.net/21.15107/rcub_ibiss_1375 .

TY  - JOUR
AU  - Adžić, Miroslav
AU  - Niciforović, Ana
AU  - Vucić, Vesna
AU  - Nešković-Konstantinović, Zora B.
AU  - Spasić, Snezana D
AU  - Jones, David R
AU  - Radojcić, Marija B
AU  - Spasić, Mihajlo
PY  - 2006
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/1655
AB  - There is a well-established role for reactive oxygen and nitrogen species, chronic inflammation and immune response in the pathogenesis of breast cancer. Complex interactions between breast cancer cells and surrounding blood vessels are prerequisites for cancer growth and invasion. Reports in the literature concerning the systemic response to, and the effect of, common breast cancer therapy on NF-kappa B and antioxidative defence enzyme expression and activity under clinical conditions are scarce. We determined these parameters in whole blood cell lysate from 16 women with breast cancer before and after combined (cyclophosphamide, doxorubicin, 5-fluorouracil; CAF) therapy and compared the results with 16 healthy women. Significantly higher levels of NF-kappa B and Mn-SOD (both their protein level and their activity) were found in breast cancer patients before and after CAF therapy, in comparison with healthy women. In parallel measurements, no change in the level or activity of catalase (CAT) was detected. According to our findings, it appears that breast cancer creates conditions that increase the level of hydrogen peroxide in the circulating cells and that the applied CAF therapy fails to compensate, therefore creating systemic conditions that favour survival and invasion of breast cancer cells.
T2  - Redox Report
T1  - Systemic NF-kappa B activation in blood cells of breast cancer patients
IS  - 1
VL  - 11
EP  - 44
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_1655
ER  - 

@article{
author = "Adžić, Miroslav and Niciforović, Ana and Vucić, Vesna and Nešković-Konstantinović, Zora B. and Spasić, Snezana D and Jones, David R and Radojcić, Marija B and Spasić, Mihajlo",
year = "2006",
abstract = "There is a well-established role for reactive oxygen and nitrogen species, chronic inflammation and immune response in the pathogenesis of breast cancer. Complex interactions between breast cancer cells and surrounding blood vessels are prerequisites for cancer growth and invasion. Reports in the literature concerning the systemic response to, and the effect of, common breast cancer therapy on NF-kappa B and antioxidative defence enzyme expression and activity under clinical conditions are scarce. We determined these parameters in whole blood cell lysate from 16 women with breast cancer before and after combined (cyclophosphamide, doxorubicin, 5-fluorouracil; CAF) therapy and compared the results with 16 healthy women. Significantly higher levels of NF-kappa B and Mn-SOD (both their protein level and their activity) were found in breast cancer patients before and after CAF therapy, in comparison with healthy women. In parallel measurements, no change in the level or activity of catalase (CAT) was detected. According to our findings, it appears that breast cancer creates conditions that increase the level of hydrogen peroxide in the circulating cells and that the applied CAF therapy fails to compensate, therefore creating systemic conditions that favour survival and invasion of breast cancer cells.",
journal = "Redox Report",
title = "Systemic NF-kappa B activation in blood cells of breast cancer patients",
number = "1",
volume = "11",
pages = "44",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_1655"
}

Adžić, M., Niciforović, A., Vucić, V., Nešković-Konstantinović, Z. B., Spasić, S. D., Jones, D. R., Radojcić, M. B.,& Spasić, M.. (2006). Systemic NF-kappa B activation in blood cells of breast cancer patients. in Redox Report, 11(1).
https://hdl.handle.net/21.15107/rcub_ibiss_1655

Adžić M, Niciforović A, Vucić V, Nešković-Konstantinović ZB, Spasić SD, Jones DR, Radojcić MB, Spasić M. Systemic NF-kappa B activation in blood cells of breast cancer patients. in Redox Report. 2006;11(1):null-44.
https://hdl.handle.net/21.15107/rcub_ibiss_1655 .

Adžić, Miroslav, Niciforović, Ana, Vucić, Vesna, Nešković-Konstantinović, Zora B., Spasić, Snezana D, Jones, David R, Radojcić, Marija B, Spasić, Mihajlo, "Systemic NF-kappa B activation in blood cells of breast cancer patients" in Redox Report, 11, no. 1 (2006),
https://hdl.handle.net/21.15107/rcub_ibiss_1655 .

TY  - JOUR
AU  - Vučić, Vesna
AU  - Adžić, Miroslav
AU  - Nićiforović, Ana
AU  - Tišma, Nevena
AU  - Ruždijić, Sabera
AU  - Radojčić, Marija B.
PY  - 2004
PY  - 2004
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/33
AB  - Despite the significant advances in cancer chemotherapy, radiotherapy still remains a method of choice for treatment of metastatic human prostate cancer. This study presents quantitative analysis of 60Co gamma-radiation effects on cell growth and cell death of metastatic human prostate cancer PC-3 cell line, performed in time (24-72h) and dose (2-20 Gy) dependent manner. The irradiated PC-3 cells were mostly dying by necrosis at late time intervals (72h), while apoptotic cell death was negligible. The EC50 or 50% of cytotoxicity was not achieved within the radiation doses used (2-20 Gy), but significant cell growth inhibition with IC50 of 10.4 Gy was observed. It is concluded that the increase in the radiation dose may have an important cytostatic effect, but for the complete eradication of metastatic prostate cancer novel cytotoxic drugs and radiosensitizers should be introduced as adjuvant.
AB  - Uprkos značajnom napretku u hemoterapiji kancera, radioterapija ostaje metod izbora u tretmanu metastaziranog kancera prostate. Ovaj rad predstavlja kvantitativnu analizu efekata 60Co gama zračenja na ćelijski rasti i ćelijsku smrt PC-3 ćelijske linije humanog kancera prostate, pri čemu je praćena vremenska (2-72h) i dozna zavisnost (2-20 Gy). Ozračene PC-3 ćelije su uglavnom umirale nekrozom u kasnijem vremenskom intervalu (72h), dok je apoptoza bila zanemarljiva. Vrednost EC50 odnosno 50% citotoksičnosti nije dostignuta primenjenim dozama, ali je ustanovljena značajna inhibicija ćelijskog rasta, sa vrednošću IC50 od 10.4 Gy. Zaključeno je da povećanje doze može imati značajan citostatički efekat ali da je za kompletno odstranjivanje metastaziranog kancera prostate neophodno uvođenje novih citotoksičnih agenasa ili radiosenzitera kao adjuvanata.
T2  - Jugoslovenska medicinska biohemija
T1  - Ćelijska smrt u ozračenim ćelijama kancera prostate analizirana protočnom citometrijom
T1  - Cell death in irradiated prostate cancer cells assessed by flow cytometry
IS  - 4
VL  - 23
SP  - 343
EP  - 350
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_33
ER  - 

@article{
author = "Vučić, Vesna and Adžić, Miroslav and Nićiforović, Ana and Tišma, Nevena and Ruždijić, Sabera and Radojčić, Marija B.",
year = "2004, 2004",
abstract = "Despite the significant advances in cancer chemotherapy, radiotherapy still remains a method of choice for treatment of metastatic human prostate cancer. This study presents quantitative analysis of 60Co gamma-radiation effects on cell growth and cell death of metastatic human prostate cancer PC-3 cell line, performed in time (24-72h) and dose (2-20 Gy) dependent manner. The irradiated PC-3 cells were mostly dying by necrosis at late time intervals (72h), while apoptotic cell death was negligible. The EC50 or 50% of cytotoxicity was not achieved within the radiation doses used (2-20 Gy), but significant cell growth inhibition with IC50 of 10.4 Gy was observed. It is concluded that the increase in the radiation dose may have an important cytostatic effect, but for the complete eradication of metastatic prostate cancer novel cytotoxic drugs and radiosensitizers should be introduced as adjuvant., Uprkos značajnom napretku u hemoterapiji kancera, radioterapija ostaje metod izbora u tretmanu metastaziranog kancera prostate. Ovaj rad predstavlja kvantitativnu analizu efekata 60Co gama zračenja na ćelijski rasti i ćelijsku smrt PC-3 ćelijske linije humanog kancera prostate, pri čemu je praćena vremenska (2-72h) i dozna zavisnost (2-20 Gy). Ozračene PC-3 ćelije su uglavnom umirale nekrozom u kasnijem vremenskom intervalu (72h), dok je apoptoza bila zanemarljiva. Vrednost EC50 odnosno 50% citotoksičnosti nije dostignuta primenjenim dozama, ali je ustanovljena značajna inhibicija ćelijskog rasta, sa vrednošću IC50 od 10.4 Gy. Zaključeno je da povećanje doze može imati značajan citostatički efekat ali da je za kompletno odstranjivanje metastaziranog kancera prostate neophodno uvođenje novih citotoksičnih agenasa ili radiosenzitera kao adjuvanata.",
journal = "Jugoslovenska medicinska biohemija",
title = "Ćelijska smrt u ozračenim ćelijama kancera prostate analizirana protočnom citometrijom, Cell death in irradiated prostate cancer cells assessed by flow cytometry",
number = "4",
volume = "23",
pages = "343-350",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_33"
}

Vučić, V., Adžić, M., Nićiforović, A., Tišma, N., Ruždijić, S.,& Radojčić, M. B.. (2004). Ćelijska smrt u ozračenim ćelijama kancera prostate analizirana protočnom citometrijom. in Jugoslovenska medicinska biohemija, 23(4), 343-350.
https://hdl.handle.net/21.15107/rcub_ibiss_33

Vučić V, Adžić M, Nićiforović A, Tišma N, Ruždijić S, Radojčić MB. Ćelijska smrt u ozračenim ćelijama kancera prostate analizirana protočnom citometrijom. in Jugoslovenska medicinska biohemija. 2004;23(4):343-350.
https://hdl.handle.net/21.15107/rcub_ibiss_33 .

Vučić, Vesna, Adžić, Miroslav, Nićiforović, Ana, Tišma, Nevena, Ruždijić, Sabera, Radojčić, Marija B., "Ćelijska smrt u ozračenim ćelijama kancera prostate analizirana protočnom citometrijom" in Jugoslovenska medicinska biohemija, 23, no. 4 (2004):343-350,
https://hdl.handle.net/21.15107/rcub_ibiss_33 .

TY  - JOUR
AU  - Vučić, Vesna
AU  - Nićiforović, Ana
AU  - Adžić, Miroslav
AU  - Tišma, Nevena
AU  - Janković, Dragana
AU  - Ruždijić, Sabera
AU  - Radojčić, Marija B.
PY  - 2003
PY  - 2003
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/373
AB  - Background: Prostate cancer is the first as an incidence and the second as a cause of the oncologic mortality in the male population. There is a broad range of possibilities in the prostate cancer therapy. However, there is also much controversy on the most appropriate treatment in the various stages of the disease. Advanced disease is mostly treated by radiation therapy, sometimes in combination with hormone or chemotherapy. Irradiation induces damage of cell biomolecules, which can lead to the arrest in cell division, or to apoptotic or necrotic cell death. The aim of this study was to determine the dose dependence of radiation-induced cell death in two human prostate cancer cell lines, and to define the form of death of these cells. Methods: Human prostate cancer cell lines PC-3 and DU-145 were irradiated with 2 - 30 Gy from 60 Co g-source, at the dose rate of 20 Gy/h. The effect of irradiation on cell viability, morphology and DNA structure were followed 24 - 72 hours after treatment. Cells were analyzed by trypan blue exclusion assay, flow cytometry and DNA gel electrophoresis. Simultaneous staining of cells with Annexin V-FITC and propidium iodide enabled distinction of early apoptosis from late apoptosis and/or necrosis. Results: The results of trypan blue staining indicated that radiation-induced cell death was both time and dose dependent process. According to flow-cytometry and DNA fragmentation assay, necrosis was the prevailing form of the radiation-induced cell death in both PC-3 and DU-145 cells. The apoptosis occurred in insignificant number of cells, probably due to the mutant p53 gene present in both cell lines. The cell necrosis was dose dependent and was most pronounced 72 hours post treatment. Conclusion The prevailing form of radiation-induced PC-3 and DU-145 cell death is necrosis. Both PC-3 and DU-145 are rather radioresistant cell lines, as the dose necessary to induce 50% decrease in viable cell number is about 10 Gy.
T2  - Archive of Oncology
T1  - Radiation-induced effects in PC-3 and DU-145 human prostate cancer cells
IS  - 3
VL  - 11
SP  - 197
EP  - 197
UR  - https://hdl.handle.net/21.15107/rcub_ibiss_373
ER  - 

@article{
author = "Vučić, Vesna and Nićiforović, Ana and Adžić, Miroslav and Tišma, Nevena and Janković, Dragana and Ruždijić, Sabera and Radojčić, Marija B.",
year = "2003, 2003",
abstract = "Background: Prostate cancer is the first as an incidence and the second as a cause of the oncologic mortality in the male population. There is a broad range of possibilities in the prostate cancer therapy. However, there is also much controversy on the most appropriate treatment in the various stages of the disease. Advanced disease is mostly treated by radiation therapy, sometimes in combination with hormone or chemotherapy. Irradiation induces damage of cell biomolecules, which can lead to the arrest in cell division, or to apoptotic or necrotic cell death. The aim of this study was to determine the dose dependence of radiation-induced cell death in two human prostate cancer cell lines, and to define the form of death of these cells. Methods: Human prostate cancer cell lines PC-3 and DU-145 were irradiated with 2 - 30 Gy from 60 Co g-source, at the dose rate of 20 Gy/h. The effect of irradiation on cell viability, morphology and DNA structure were followed 24 - 72 hours after treatment. Cells were analyzed by trypan blue exclusion assay, flow cytometry and DNA gel electrophoresis. Simultaneous staining of cells with Annexin V-FITC and propidium iodide enabled distinction of early apoptosis from late apoptosis and/or necrosis. Results: The results of trypan blue staining indicated that radiation-induced cell death was both time and dose dependent process. According to flow-cytometry and DNA fragmentation assay, necrosis was the prevailing form of the radiation-induced cell death in both PC-3 and DU-145 cells. The apoptosis occurred in insignificant number of cells, probably due to the mutant p53 gene present in both cell lines. The cell necrosis was dose dependent and was most pronounced 72 hours post treatment. Conclusion The prevailing form of radiation-induced PC-3 and DU-145 cell death is necrosis. Both PC-3 and DU-145 are rather radioresistant cell lines, as the dose necessary to induce 50% decrease in viable cell number is about 10 Gy.",
journal = "Archive of Oncology",
title = "Radiation-induced effects in PC-3 and DU-145 human prostate cancer cells",
number = "3",
volume = "11",
pages = "197-197",
url = "https://hdl.handle.net/21.15107/rcub_ibiss_373"
}

Vučić, V., Nićiforović, A., Adžić, M., Tišma, N., Janković, D., Ruždijić, S.,& Radojčić, M. B.. (2003). Radiation-induced effects in PC-3 and DU-145 human prostate cancer cells. in Archive of Oncology, 11(3), 197-197.
https://hdl.handle.net/21.15107/rcub_ibiss_373

Vučić V, Nićiforović A, Adžić M, Tišma N, Janković D, Ruždijić S, Radojčić MB. Radiation-induced effects in PC-3 and DU-145 human prostate cancer cells. in Archive of Oncology. 2003;11(3):197-197.
https://hdl.handle.net/21.15107/rcub_ibiss_373 .

Vučić, Vesna, Nićiforović, Ana, Adžić, Miroslav, Tišma, Nevena, Janković, Dragana, Ruždijić, Sabera, Radojčić, Marija B., "Radiation-induced effects in PC-3 and DU-145 human prostate cancer cells" in Archive of Oncology, 11, no. 3 (2003):197-197,
https://hdl.handle.net/21.15107/rcub_ibiss_373 .