This study was conducted to investigate whether agmatine (AGM) provides protection against oxidative stress induced by treatment with chlorpromazine (CPZ) in Wistar rats. In addition, the role of reactive oxygen species and efficiency of antioxidant protection in the brain homogenates of forebrain cortexes prepared 48 h after treatment were investigated. Chlorpromazine was applied intraperitoneally (i.p.) in single dose of 38.7 mg/kg body weight (BW) The second group was treated with both CPZ and AGM (75 mg/kg BW). The control group was treated with 0.9% saline solution in the same manner. All tested compounds were administered i.p. in a single dose. Rats were sacrificed by decapitation 48 h after treatment Treatment with AGM significantly attenuated the oxidative stress parameters and restored antioxidant capacity in the forebrain cortex. The data indicated that i.p. administered AGM exerted antioxidant action in CPZ-treated animals. Moreover, reactive astrocytes and microglia may contribute to secondary nerve-cell damage and participate in the balance of destructive vs. protective actions involved in the pathogenesis after poisoning.
Changed oxidative stress parameters in patients poisoned with chlorpromazine indicate involvement of oxidative stress in the toxicity mechanism(s) of chlorpromazine.
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.
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