Hepatoprotective effect of melatonin in carbon tetrachloride [CCl[4] hepatic intoxication model in rat

ABSTRACT

An enormous amount of data has been published in recent years demonstrating melatonin's defensive role against toxic free radicals. The protective effect of melatonin on experimental oxidative hepatic impairment in rats was studied in this investigation. The hepatic toxicity model in rats was successfully induced by subcutaneous [sc] injection of carbon tetrachloride [CCl[4]] [0.5ml/kg/day] for 6 weeks. Meanwhile, at the beginning of injection of carbon tetrachloride [CCl[4]], melatonin [25mg/kg] was subcutaneously [sc] administered to the rats in treatment group daily for 6 weeks and rats in normal and melatonin control groups were injected by olive oil or melatonin only, respectively. The hepatoprotective effects of melatonin were assessed by examining the hepato-histological changes and by measuring serum levels of aspartate aminotransferase [AST], alanine aminotransferase [ALT] and total bilirubin as well as white blood cell [WBCs], red blood cell [RBCs] and hemoglobin [HB%] values. In addition, immunohistochemical labeling of proliferating cell nuclear antigen [PCNA] was used for detection of hepatocytes proliferation. Concomitant administration of melatonin preserved the normal histological structure of liver and significantly ameliorated the CCl[4]-treated rats. Moreover, melatonin supplement could also reduce the elevated serum levels of ALT, AST and total bilirubin, the increased WBCs count as well as the overexpression of PCNA in rats with hepatic injury caused by CCl[4]. In conclusion, melatonin co-treatment could effectively protect against the oxidative hepatic impairment in CCl[4]-induced rats as evidenced by decreasing both the structural and functional injury of hepatocytes and may be a therapeutic choice in cirrhotic patients