Melatonin modulates the oxidant-antioxidant imbalance during N-nitrosodiethylamine induced hepatocarcinogenesis in rats

PURPOSE: Melatonin, the principle hormone of pineal gland plays an important role in several biological processes. The effects of melatonin on hepatic marker enzymes [ aspartate and alanine transaminases ( AST and ALT)], lipid peroxides [ thiobarbituric acid reactive substances ( TBARS)] and antioxidants [ reduced glutathione ( GSH), glutathione peroxidase ( GPx) and glutathione- S- transferase ( GST)] during N- nitrosodiethylamine ( NDEA) - induced hepatocarcinogenesis in rats were studied. METHODS: Male albino Wistar rats of body weight 150- 170 g were divided into four groups of six animals each. Group I animals served as control, Group II animals received single intraperitoneal injection of NDEA at a dose of 200 mg/ kg body weight followed by weekly subcutaneous injections of CCl4 at a dose of 3 mL/ kg body weight. Group III animals were treated as in Group II and melatonin ( 5 mg/ kg body weight) was administered intraperitoneally. Group IV animals received melatonin alone at the same dose as Group III animals. RESULTS: A significant increase in the activities of serum AST and ALT was observed in NDEA treated rats when compared with control animals. Melatonin administered rats showed a significant decrease in the activities of these enzymes when compared with NDEA treated animals. In the liver of NDEA- treated animals, decreased lipid peroxidation associated with enhanced antioxidant levels was observed. Administration of melatonin positively modulated these changes. CONCLUSION: Our results indicate that melatonin exerts chemopreventive effect by restoring the activities of hepatic marker enzymes and reversing the oxidant-antioxidant imbalance during NDEA- induced hepatocarcinogenesis.