title: Effects of agmatine on chlorpromazine toxicity in the liver of Wistar rats: the possible role of oxidant/antioxidant imbalance.
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.
authors: Military Medical Center "Karaburma", Belgrade, Serbia.
authors: Dejanovic
authors: D
authors: Bratislav
authors: Lavrnja
authors: L
authors: Irena
authors: Ninkovic
authors: N
authors: Milica
authors: Stojanovic
authors: S
authors: Ivana
authors: Djuric
authors: D
authors: Ana
authors: Dilber
authors: D
authors: Sanda
authors: Stevanovic
authors: S
authors: Ivana
mesh_terms: D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D014150:Antipsychotic Agents / Q000633:toxicity; D002746:Chlorpromazine / Q000633:toxicity*; D008099:Liver / Q000187:drug effects*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D014150:Antipsychotic Agents; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D000376:Agmatine; D002746:Chlorpromazine