ABSTRACT
As the liver is the predominant site of drug clearance, biotransformation and excretion, so drugs are considered as a frequent cause of liver injury ranging from asymptomatic elevation of liver enzymes activities to fulminant hepatic failure. Among these drugs are the chronically used phenothiazines psychotropic drugs like Chlorpromazine [CPZ] which known to produce cholestatic liver disease. Melatonin [MT] has been shown to reduce the toxicity and increase the efficacy of a large number of drugs whose side effects are well documented and provide protective effects in many organs, including liver, against many types of insult. Evaluation of the possible protective effect of orally administered melatonin against CPZ-induced liver injury in rats. The hepatoprotective effect of melatonin were studied through the treatment of rats with single dose [10 mg/Kg] orally, seven days before and during the period of CPZ treatment, and seven days after the induction of suspected hepatotoxicity. The parameters of oxidative stress, malondialdehyde [MDA] and glutathione [GSH] were evaluated in liver tissue homogenate. The activities of liver enzymes alaninaminotransferase [ALT] and aspartate aminotransferase [AST] in serum as indicator of liver injury, in addition to serum level of bilirubin [total and conjugated] were assessed. Analysis of data showed significant attenuation of oxidative stress parameter as evidenced by lowering MDA levels in tissue homogenate by melatonin while not affecting GSH levels. Serum activities of ALT, AST and serum bilirubin were normalized with both pre-treatment and post-treatment with melatonin. The data revealed that post-treatments with both saline and melatonin restore hepatic activity, however, melatonin showed significant reduction in ALT activity and bilirubin level than saline post-treatment. Additionally, the histologically evident damage in the liver has been improved. The presented data indicated that orally administered melatonin at pharmacological doses protects against CPZ-induced liver injury in rats