Protective effect of melatonin against chlorpromazine-induced liver disease in rats

OBJECTIVE: To evaluate the possible protective effect of orally administered melatonin against Chlorpromazine (CPZ)-induced liver disease in rats.

METHODS: We performed this study in the College of Pharmacy, University of Baghdad during the period from May to October 2004. The hepatoprotective effect of melatonin was studied through treatment of rats with single dose (10 mg Kg-1) orally, 7 days before and during the period of CPZ treatment, and 7 days after the induction of suspected hepatotoxicity. The parameters of oxidative stress, malondialdehyde (MDA) and glutathione (GSH) in liver tissue homogenate, activities of the liver aminotransferases, alanine transaminase (ALT) and aspartate transaminase (AST) in serum, in addition to serum level of bilirubin (total and conjugated) were evaluated. Liver tissue sections were examined to follow histological changes.

RESULTS: Analysis of data showed that treatment with melatonin significantly attenuated the oxidative stress parameters as evidenced by lowering MDA levels in tissue homogenate while not affecting GSH levels. Serum activities of ALT, AST and serum bilirubin were normalized with both pre-treatment and post-treatment with melatonin. 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, histological evaluation revealed improvement of liver damage in this respect.

CONCLUSION: The presented data indicated that orally administered melatonin in pharmacological doses protects against CPZ-induced liver disease in rats.