Carbamazepine provoked hepatotoxicity: attenuation by vitamin C

Abstract

Thaakur Santhrani, Eswaran Maheswari, Ganesan Rajalakshmi Saraswathy

Antiepileptic drugs are reported to be potentially hepatotoxic. The present study evaluates the hepatoprotective activity of vitamin C against carbamazepine induced hepatotoxicity. Rats were treated with carbamazepine (50 mg/kg p.o.) and carbamazepine supplemented with 50, 100 and 200 mg/kg vitamin C for 45 days, after which blood samples were collected and subjected to liver function tests. Animals were sacrificed, liver was isolated, weighed and the levels of antioxidants were estimated along with histopathological investigations. Serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, alkaline phosphatase, bilirubin, lipid peroxidation, absolute and relative liver weights were significantly elevated, whereas serum levels of albumin, total protein and body weight was decreased in the carbamazepine treated animals. Carbamazepine also caused vacuolar degeneration, centrilobular congestion and hepatic necrosis as evidenced from histopathological report. Vitamin C significantly reduced the levels of serum transaminases, alkaline phosphatase, bilirubin and liver weight along with an increase in total protein, albumin and body weight. It was also observed that vitamin C increased the glutathione content, reduced lipid peroxidation in liver samples and also reversed the carbamazepine induced histopathological abnormalities. Carbamazepine’s toxic metabolite epoxide induces oxidative stress; vitamin C by virtue of its antioxidant capacity reduced the oxidative stress and reversed the carbamazepine induced hepatic damage.