Attenuation of acute and chronic liver injury by melatonin in rats

Oxidative stress produced by free radicals has been implicated in the pathogenesis of acute liver injury. The aim of our study was to investigate whether melatonin, a potent antioxidant, could attenuate acute and chronic hepatic injury in rats. Acute liver injury was induced by two consecutive intra peritoneal (i.p.) injections of thioacetamide (TAA; 300 mg/kg, i.p.) at 24 h intervals. Chronic liver injury was induced by (TAA, i.p. injections for 6 weeks twice weekly, 50 mg/kg). Treatment with melatonin (3 mg/kg/daily, i.p.) was initiated 24 h prior to and for 6 weeks post TAA intake. Rats in normal control group received intra-peritoneal injections of normal saline at the same dose and frequency as those in treatment groups. At the end of experiment, animals were sacrificed, liver was removed and weighed, and ratio to body weight was calculated. Serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), reduced glutathione (GSH) and malondialdehyde (MDA) concentration in liver homogenates were assessed. We found that the acute and chronic experiments, liver weight, as well as liver weight/body weight ratio, ALT, AST, GSH and MDA concentration were lower in rats treated with TAA + melatonin compared to acute and chronic TAA groups. Liver histology was significantly improved and the mortality in the melatonin-treated rats was decreased indicating decreased oxidative stress and inflammation. In conclusion both models results suggest that melatonin may be utilized to reduce liver injury associated with oxidative stress.