Background and purpose: Valproic acid (VPA) is used worldwide as a major drug in the intervention of epilepsy and in control of several kinds of seizures. The aim of our investigation was to evaluate the nephrotoxic potential of VPA and protective effects of zinc and selenium against VPA-induced nephrotoxicity in Wistar rats.

Materials and methods: In this study, the animals were divided into five groups: control, VPA (200 mg/kg IP), VPA + Zn (10 mg/kg IP), PA + Se (1 mg/kg IP), and VPA + Zn + Se. After the administration of VPA for 4 consecutive weeks, the animals were killed and kidney tissues were separated. Finally, oxidative stress markers including glutathione (GSH) content, lipid peroxidation (LPO), protein carbonyl (PCO) were measured and blood was taken for measuring biochemical markers (BUN and Cr).

Results: The administration of VPA for 4 consecutive weeks resulted in an increase in kidney marker (BUN and Cr). Also, oxidative stress was evident in VPA group by increased lipid peroxidation (LPO), protein carbonyl (PCO) and glutathione (GSH) oxidation. Zn and Se administration was able to protect against deterioration in kidney markers and suppressed the increase in oxidative stress markers.

Conclusion: Our study showed the critical role of oxidative damage in Valproate-induced nephrotoxicity that markedly inhibited by administration of Zn and Se. Therefore, Zn and Se supplementation could be suggested for prevention of valproate-induced nephrotoxicity.