Biochemical basis of sodium valproate hepatotoxicity and renal tubular disorder: Time dependence of peroxidative injury

Mice fed with sodium valproate for 7, 14 and 21 days were evaluated for hepatotoxicity and renal tubular disorder. The drug was administered as an aqueous solution with an increasing concentration up to five days gradually reaching up to 0.71% w/v, which persisted throughout the study period. Mice fed with sodium valproate for 7, 14 and 21 days showed, marked hepatic injury and renal tubular disorder, evidenced by increased levels of malondialdehyde as a measure of lipid peroxidation. Administration of sodium valproate affected the glutathione contents both in liver and kidney tissue at all the three time points. However, this reduction in glutathione concentration was more pronounced in kidney when compared to control group. These results support the hypothesis that lipid peroxidation mediates the effect of sodium valproate on liver and kidney. Furthermore, the valproate induced toxicity is time related and the increase in lipid peroxide levels and depletion of glutathione occur time dependent even if the dose is clinically appropriate. (C) 1997 The Italian Pharmacological Society.