Hepatoprotective and antioxidant activity of N-acetyl cysteine in carbamazepine-administered rats

Abstract

Objectives: The present study evaluates the hepatoprotective activity of N-acetyl cysteine (NAC) against carbamazepine (CBZ)-induced hepatotoxicity.

Materials and methods: Rats were treated with CBZ (50 mg/kg p.o.) and CBZ supplemented with NAC 50, 100 and 200 mg/kg for 45 days, after which blood samples were collected and subjected to liver function tests. Animals were killed, liver was separated, weighed and the levels of antioxidants and liver enzymes were estimated. In addition, histopathological investigation was also performed.

Results: Serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate (SGOT) transaminase, alkaline phosphatase (ALP), bilirubin, lipid peroxidation, absolute and relative liver weights were significantly (P < 0.05) elevated, whereas serum levels of albumin, total protein and body weight were decreased in the CBZ-treated animals. CBZ also produced vacuolar degeneration, centrilobular congestion and hepatic necrosis as evidenced from histopathological report. NAC significantly reduced the levels of serum transaminase, ALP, bilirubin and liver weight and increased the levels of total protein, albumin and body weight.

Conclusion: It was observed that NAC increased the glutathione (GSH) content, reduced lipid peroxidation and reversed the CBZ-induced histopathological abnormalities. CBZ-induced hepatotoxicity may be due its toxic epoxide metabolite-induced oxidative stress.

Keywords: Carbamazepine; N-acetyl cysteine; hepatotoxicity; oxidative stress.

Figure 1

Effect of carbamazepine on liver histopathology a - Control b - CBZ Effect of N-acetyl cysteine on carbamazepine-induced alterations in liver histopathology c - CBZ + NAC (50 mg/kg) d - CBZ + NAC (100 mg/kg) e - CBZ + NAC (200 mg/kg)