Valporic Acid-Induced Hepatotoxicity in Rats

Abstract

Background: The use of valproic acid (VPA) as therapy for epileptic and other neuropsychiatric disorders may cause hepatotoxicity. Selenium (Se), a component of selenoproteins, which performs important enzymic functions, may protect biomolecules from damage. This study assessed the protective effect of Se against VPA-induced hepatotoxicity in Wistar rats. Methods: Thirty-two adult Wistar rats of both sexes (160 ± 20 g) were divided into four groups of n = 8. Groups 1 (Control), 2, and 3 were orally administered with normal saline (0.2 mL), Se (0.1 mg/kg/day), and VPA (200 mg/kg/day) for 30 days, respectively. Group 4 was orally administered with Se (0.1 mg/kg/day) and VPA (200 mg/kg/day) for 30 days. After treatment, the rats were weighed and anesthetized. Blood samples were collected and analyzed for serum biochemical parameters. Liver samples were weighed and assessed for biochemical markers and histology. Results: Body weight was significantly (P < 0.01) decreased, whereas liver weight was significantly (P < 0.01) increased in VPA administered rats. VPA caused significant (P < 0.001) increases in serum and liver aminotransferases, alkaline phosphatase, gamma-glutamyl transferase, lactate dehydrogenase, conjugated bilirubin, total bilirubin, total cholesterol, triglyceride, low-density lipoprotein cholesterol, and malondialdehyde levels when compared to control. VPA produced significant (P < 0.001) decreases in liver glutathione, catalase, superoxide dismutase, glutathione peroxidase and serum high density lipoprotein cholesterol levels when compared to control. Hepatocyte necrosis and fatty change were observed in VPA- administered rats. Se supplementation significantly (P < 0.01) reversed VPA-induced hepatotoxicity. Conclusion: Se seems effective against VPA-induced hepatotoxicity.