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


CONCLUSIONS
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.
Dakshayani
K B
KB
Department of Biochemistry, Annamalai University, Annamalainagar-608 002, Tamil Nadu, India.
Subramanian
P
P
Manivasagam
T
T
Essa
M Mohamed
MM
Manoharan
S
S
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004052:Diethylnitrosamine / Q000633:toxicity; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D016877:Oxidants / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D016877:Oxidants; D004052:Diethylnitrosamine; D008550:Melatonin