Zinc Deficiency and Oxidative Stress Involved in Valproic Acid Induced Hepatotoxicity: Protection by Zinc and Selenium Supplementation.

Ahangar, Nematollah; Naderi, Maloos; Noroozi, Abdolali; Ghasemi, Maryam; Zamani, Ehsan; Shaki, Fatemeh

Valproic acid (VPA) is an antiepileptic drug, which its usage is limited due to its hepatotoxicity. The present study was conducted to investigate the efficacy of zinc (Zn) and selenium (Se), necessary trace elements, against VPA-induced hepatotoxicity in Wistar rats. The animals were divided into five groups: control, VPA 200 mg/kg, VPA Zn (100 mg/kg), VPA Se (100 mg/kg), and VPA Zn Se. The administration of VPA for four consecutive weeks resulted in decrease in serum level of Zn in rats. Also, an increase in liver marker enzymes (ALT and AST) and also histological changes in liver tissue were shown after VPA administration. Oxidative stress was evident in VPA group by increased lipid peroxidation (LPO), protein carbonyl (PCO), glutathione (GSH) oxidation, and reducing total antioxidant capacity. Zn and Se (100 mg/kg) administration was able to protect against deterioration in liver enzyme, abrogated the histological change in liver tissue, and suppressed the increase in oxidative stress markers. Zn and combination of Zn plus Se treatment showed more protective effects than Se alone. These results imply that Zn and Se should be suggested as effective supplement products for the prevention of VPA-induced hepatotoxicity.

ZINC deficiency diseases; OXIDATIVE stress; VALPROIC acid; HEPATOTOXICOLOGY; TRACE element analysis; LABORATORY rats; LIPID peroxidation (Biology)

Biological Trace Element Research, 2017, Vol 179, Issue 1, p102

0163-4984

Academic Journal

10.1007/s12011-017-0944-z