Protective effects of melatonin against carbon tetrachloride hepatotoxicity in rats

Melatonin is an indolamine, mainly secreted by the pineal gland into the blood of mammalian species. The potential for protective effects of melatonin on carbon tetrachloride (CCl₄)-induced acute liver injury in rats was investigated in this work. CCl₄ exerts its toxic effects by generation of free radicals; it was intragastrically administered to male Wistar rats (4 g kg^-1 body weight) at 20 h before the animals were decapitated. Melatonin (15 mg kg^-1 body weight) was administered intraperitoneally three times: 30 min before and at 2 and 4 h after CCl ₄ injection. Rats injected with CCl₄ alone showed significant lipid and hydropic dystrophy of the liver, massive necrosis of hepatocytes, marked increases in free and conjugated bilirubin levels, elevation of hepatic enzymes (alanine aminotransferase and aspartate aminotransferase) in plasma, as well as NO accumulation in liver and in blood. Melatonin administered at a pharmacological dose diminished the toxic effects of CCl ₄. Thus it decreased both the structural and functional injury of hepatocytes and clearly exerted hepatoprotective effects. Melatonin administration also reduced CCl₄-induced NO generation. These findings suggest that the effect of melatonin on CCl₄-induced acute liver injury depends on the antioxidant action of melatonin.