Therapeutic effect of melatonin on carbon tetrachloride-induced acute liver injury in rats

The therapeutic effect of melatonin on acute liver injury was examined in r ats intoxicated with carbon tetrachloride (CCl4). Melatonin (10, 50, or 100 mg/kg body weight [BW]) was intraperitoneally administered to male Wistar rats 6 hr after intraperitoneal injection of CCl4 (1.6 g/kg BW) at which ti me an apparent liver injury occurred. This post-melatonin administration do se dependently prevented the progression of liver injury at 24 hr after CCl 4 injection, judging from the levels of serum transaminases, indices of liv er cell damage. Rats injected with CCl4 alone showed an increase in liver l ipid peroxide (LPO) content and a decrease in liver reduced glutathione con tent at 6 and 24 hr after the injection. The post-melatonin administration dose dependently ameliorated both changes found at 24 hr after CCl4 injecti on. Rats injected with CCl4 alone showed an increase in liver triglyceride (TG) content and decreases in serum TG concentration and liver tryptophan 2 ,3-dioxygenase (TDO) activity, a marker of the inhibition of liver protein synthesis by CCl4, at 6 and 24 hr after the injection, and also a decrease in serum albumin concentration at 24 hr. The changes in serum TG, albumin c oncentration, liver TG content, and TDO activity found at 24 hr after CCl4 injection were not ameliorated by the post-administration of melatonin. The same administration of melatonin dose dependently reduced liver LPO conten t in CCl4-untreated rats. These results indicate that melatonin exerts a th erapeutic effect on CCl4-induced acute liver injury in rats, possibly throu gh its antioxidant action.