Attenuation of N-nitrosodiethylamine-induced hepatocellular carcinogenesis by a novel flavonol-Morin.
Morin (3,5,7,2',4'-pentahydroxyflavone), a plant-derived flavonoid belonging to the subclass of flavonol is believed to play a role in chemoprevention and cancer chemotherapy. In this study, we found that the cotreatment of morin (500 ppm in diet) for 16 weeks to N-nitosodiethylamine-induced (200 mg/kg bodyweight in drinking water) rats provides protection against the oxidative stress caused by the carcinogen and thereby prevents hepatocellular carcinogenesis. On administration of the carcinogen, the level of lipid peroxidation increased markedly, but was found to be significantly lowered by morin treatment. On the contrary, the antioxidant levels in both liver and serum were decreased in carcinogen-administered animals, which was improved to normalcy upon morin administration. Cotreatment with morin prevented the elevation of marker enzymes induced by N-nitrosodiethylamine. The body weight of the animals decreased and their relative liver weight increased significantly on N-nitrosodiethylamine administration when compared to control group. However, cotreatment with morin significantly prevented the decrease of the body weight and increase in relative liver weight caused by DEN. Histological observations of liver tissue too correlated with the biochemical observations. In conclusion, these findings indicate that morin prevents lipid peroxidation, hepatic cell damage and protects the antioxidant system in N-nitrosodiethylamine-induced hepatocellular carcinogenesis.
Sivaramakrishnan
Venkatabalasubramanian
V
Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, Tamilnadu, India.
Shilpa
Perumal Narasimha Moorthy
PN
Praveen Kumar
Varuvoor Rajesh
VR
Niranjali Devaraj
Sivasitambaram
S
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D002272:Carcinoembryonic Antigen / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D004052:Diethylnitrosamine; D004798:Enzymes / Q000097:blood; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use; D017665:Hydroxyl Radical / Q000378:metabolism; D008054:Lipid Peroxides / Q000097:blood / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000097:blood / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000097:blood / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000378:metabolism; D047309:Flavones
D000975:Antioxidants; D002272:Carcinoembryonic Antigen; D004052:Diethylnitrosamine; D004798:Enzymes; D005419:Flavonoids; D017665:Hydroxyl Radical; D008054:Lipid Peroxides; D013482:Superoxide Dismutase; D000509:alpha-Fetoproteins; C008548:morin; D047309:Flavones