Melatonin modulates the oxidant-antioxidant imbalance during N-nitrosodiethylamine induced hepatocarcinogenensis 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 CC1₄ 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.