Texicological, histopathological and ultrastructural study of the protective effects of some antioxidants on sodium valproate induced hepatotoxicity in rats

Valproic acid [VPA] is well known for its broad spectrum antiepileptic activity and is gaining popularity as a component in antipsychotic therapy. VPA may have limited use due to the possible risk of hepatotoxicity. The aim of the present work was to investigate the hepatotoxic effect of VPA and to evaluate the protective role of deferoxamine and L-carnitine. The levels of malonaldehyde [MDA], antioxidant enzymes [catalase and glutathione -S-transferase] and liver triglycerides were measured in the liver tissues. In addition, serum levels of liver enzymes and plasma triglycerides were measured. Histological and ultrastructural changes in the hepatocytes were studied. The results showed that, VPA- induced hepatotoxicity was in the form of micro vesicular steafosis. Biochemically, evidence of oxidative stress namely, elevated levels of MDA, catalase and glutathione -S- transferase were found. Increased levels of liver enzymes and plasma and liver triglycerides were also detected. Co-administration of deferoxamine with VPA resulted in protection of the hepatocytes against VPA induced hepatotoxicity. Co-administration of L-carnitine with VPA was associated with better results than deferoxamine histologically, ultrastructurally and biochemically. In conclusion, the use of L-carnitine as an antioxidant in protecting against valproat induced hepatotoxicity should be encouraged

Toxicological, histopathological and ultrastructural study of the protective effects of some antioxidants on sodium valproate induced hepatotoxicity in rats

Valproic acid [VPA] is well known or its broad spectrum antiepileptic activity and is gaining popularity as a component in antipsychotic therapy. VPA may have limited use due to the possible risk of hepatotoxicity. The aim of the present work was to investigate the hepatotoxic effect of VPA and to evaluate the protective role of deferoxamine and L-carmitine. The levels of malonaldehyde [MDA], antioxidant enzymes [catalase and glutathione-S-transferase] and liver triglycerides were measured in the liver tissues. In addition serum levels of liver enzymes and plasma triglycerides were measured. Histological and ultrastrucural changes in the hepatocytes were studied. The results showed that, VPA-induced hepatotoxicity was in the form of microvesicular steatosis. Biochemically, evidence of oxidative stress namely, elevated levels of MDA, catalase and glutathione-S-transferase were found. Increased levels of liver enzymes and plasma and liver triglycerides were also detected. Co-administration of deferoxamine with VPA resulted in protection of the hepatocytes against VPA induced hepatotoxicity. Co-administration of L-carnitine with VPA was associated with better results than deferoxamine histologically, ultratructurally and biochemicaly. In conclusion, the use of L-carnitine as an antioxidant in protecting against valproat induced hepatotoxiciy should be encouraged