Reversal of phenytoin induced hepatotoxicity by alpha lipoic acid in rats

Abstract

The present research task is aimed at evaluating the influence of alpha lipoic acid (ALA) against phenytoin induced hepatotoxicity. The rats were divided into five groups of six animals each. Group 1 received 0.2% carboxy methyl cellulose (CMC, p.o), group 2 received 20 mg/kg phenytoin (p.o), groups 3, 4 and 5 received 50, 100 and 200 mg/kg (p.o) of ALA in 0.2% CMC, respectively 1 h prior to phenytoin for 45 days. On the 45th day, blood samples were collected and subjected to analysis of liver function test. Animals were sacrificed, antioxidant status and lipid peroxidation were estimated in the liver samples along with histopathological investigations. Phenytoin treatment was observed to induce liver injury, which was apparent from increased serum transaminases, alkaline phosphatase (ALP) and bilirubin in blood, and lipid peroxidation in liver. Phenytoin decreased the levels of albumin, total protein, and endogenous antioxidants along with reduction in body weight. Histopathological investigation revealed phenytoin induced periportal congestion and hepatic necrosis. ALA (100 and 200 mg/kg) significantly (P < 0.001) reduced the phenytoin elevated serum enzymes, ALP, bilirubin, lipid peroxidation, liver weight and significantly increased the levels of albumin, total protein, antioxidant levels and body weight reduced by phenytoin. ALA effectively reversed the phenytoin induced histopathological changes. ALA was found to be effective against phenytoin induced hepatotoxicity.