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

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  • Bratislav Dejanovic
    Military Medical Center “Karaburma”, Belgrade, Serbia
  • Irena Lavrnja
    Institute for Biological Research “Sinisa Stankovic”, University of Belgrade, Belgrade, Serbia
  • Milica Ninkovic
    Institute for Medical Research, Military Medical Academy, Belgrade, Serbia
  • Ivana Stojanovic
    Institute for Biochemistry, Faculty of Medicine, University of Nis, Nis, Serbia
  • Ana Djuric
    Faculty of Pharmacy, Institute of Toxicology, Belgrade, Serbia
  • Sanda Dilber
    Faculty of Pharmacy, Institute of Organic Chemistry, Belgrade, Serbia
  • Ivana Stevanovic
    Institute for Medical Research, Military Medical Academy, Belgrade, Serbia

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抄録

<p>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.</p>

収録刊行物

  • Experimental Animals

    Experimental Animals 66 (1), 17-27, 2017

    公益社団法人 日本実験動物学会

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