Five-day administration of ivermectin is effective in attenuating valproic acid-induced liver toxicity in rats

Abstract

Valproic acid (VPA) is an effective and inexpensive anticonvulsant commonly prescribed as an antiepileptic. However, there is a percentage of susceptible patients who experience unwanted effects, such as weight gain and fatty liver. Ivermectin (IVM), a versatile antiparasitic, has shown potential in the treatment of non-alcoholic fatty liver disease. In this study, the potential hepatoprotective effect of ivermectin on valproic acid-induced hepatotoxicity was investigated in rats. VPA (250 mg/kg/day) was orally administered for 14 consecutive days to induce hepatocellular damage in adult Wistar rats, after which the animals were treated with a subcutaneous injection of IVM (0.4 and 1.3 mg/kg/day) for another five days. Animals receiving VPA developed obesity and microvesicular and macrovesicular steatosis. They also had increased levels of plasma triglycerides and aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase enzymes. IVM treatment significantly decreased serum triglyceride and cholesterol levels and attenuated valproic acid-induced hepatic lipid accumulation in rats. These results were confirmed by histopathological examination.