Attenuation of N-nitrosodiethylamine-induced hepatocellular carcinogenesis by a novel flavonol-Morin |
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Authors: | Sivaramakrishnan Venkatabalasubramanian Shilpa Perumal Narasimha Moorthy Praveen Kumar Varuvoor Rajesh Niranjali Devaraj Sivasitambaram |
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Affiliation: | Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, Tamilnadu, India |
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Abstract: | 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. |
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Keywords: | DEN, N-nitrosodiethylamine HCC, hepatocellular carcinoma MDA, malondialdehyde AST, aspartate transaminase ALT, alanine transaminase LDH, lactate dehydrogenase SOD, superoxide dismutase CAT, catalase GST, glutathione-S-transferase GR, glutathione reductase GPx, glutathione peroxidase LPO, lipid peroxidation TPA, 12-O-tetradecanoylphorbol-13-acetate TBARS, thiobarbituric acid reactive substances ROS, reactive oxygen species ELISA, enzyme linked immunosorbent assay AFP, α-feto protein CEA, carcinoembryonic antigen |
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