Protective Role of Melatonin and Taurine Against Carbamazepine-induced Toxicity in Freshly Isolated Rat Hepatocytes

Abstract

Carbamazepine is widely used in a broad spectrum of psychiatric and neurological disorders. Idiosyncratic hepatotoxicity is a well-known adverse reaction associated with carbamazepine. Hepatotoxicity is rare, but a real concern when initiating therapy. It was found that oxidative stress is a potential mechanism for carbamazepine-induced hepatotoxicity. Present study evaluated the hepato protective role of taurine and melatonin against carbamazepine-induced hepatotoxicity. Hepatocytes were prepared by the method of collagenase enzyme perfusion via portal vein. Cells were treated with 400 m M carbamazepine, 1 mM taurine, and 1 mM melatonin. Cell death, reactive oxygen species formation, lipid peroxidation, and mitochondrial membrane depolarization were assessed as toxicity markers and the effects of taurine and melatonin administration on them were investigated. Our results showed that carbamazepine induced oxidative stress; increased ROS formation and lipid peroxidation products and also decreased mitochondrial membrane potential (Delta psi(m)). Carbamazepine caused a decrease in cellular glutathione content and an elevation in oxidized glutathione levels. Our investigation showed that preincubation of hepatocytes with taurine (1 mM) could alleviate oxidative damages induced by carbamazepine; melatonin was also a good antioxidant to protect hepatocytes against cytotoxicity induced by carbamazepine. It may be concluded that taurine and melatonin are effective antioxidants to prevent carbamazepine-induced hepatotoxicity. Following our findings, further studies are suggested on the antioxidant effects of taurine and melatonin in patients receiving carbamazepine.