title: [Biochemical basis of valproic acid toxicity: role of oxidative stress and effects of L-carnitine].
abstract: 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.
authors.forename: I L
authors.initials: IL
authors.lastname: Bykov
authors.forename: A N
authors.initials: AN
authors.lastname: Mal'tsev
authors.forename: V A
authors.initials: VA
authors.lastname: Gurinovich
authors.forename: L I
authors.initials: LI
authors.lastname: Nefedov
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000633:toxicity*; D002331:Carnitine / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D014635:Valproic Acid / Q000633:toxicity*
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid; D002374:Catalase; D002331:Carnitine