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  - 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  - 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  - 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 . .