This work was supported by the Military Medical Academy (Project No. MФBMA/6/15–17)

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This work was supported by the Military Medical Academy (Project No. MФBMA/6/15–17)

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Effects of agmatine on chlorpromazine toxicity in the liver of Wistar rats: the possible role of oxidant/antioxidant imbalance

Dejanović, Bratislav; Lavrnja, Irena; Ninković, Milica; Stojanović, Ivana; Đurić, Ana; Dilber, Sanda; Stevanović, Ivana

(2017)

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 . .
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