[Biochemical basis of valproic acid toxicity: role of oxidative stress and effects of L-carnitine].

Reduced hepatic mitochondrial beta-oxidation and changes in L-carnitine metabolism are important biochemical manifestations of valproate (VA)-induced hepatic toxicity. Lipid peroxidation activation as a possible mechanism implicated in VA-induced damage as well as the possibility of L-carnitine (LC) attenuation of lipid peroxidation activity were studied. The level of malondialdehyde (MDA), lipid peroxide concentration and antioxidant activity (AOA), catalase activity, free S-S groups content in plasma and liver homogenates from male albino rats supplemented with VA (200 mg/kg, 8 days) and VA plus LC (100 mg/kg, 8 days) were measured. There were insignificant differences in MDA formation and catalase activity in the plasma and liver of control and VA-treated groups, however decreases in the plasma AOA activity and S-S groups level were observed in VA-treated rats. The LC administration significantly decreased liver lipid peroxide concentration and increased plasma AOA activity and S-S groups. Our results suggest that lipid peroxidation may be involved as an additional mechanism for VA-induced liver damage in rats. The potential antioxidant activity of LC may be particularly relevant in understanding the pharmacological and biochemical properties of LC in VA-induced pathologic conditions.