title: Beta-carotene prevents lipid peroxidation and red blood cell membrane protein damage in experimental hepatocarcinogenesis.
abstract: The anti-cancer efficacy of dietary beta-carotene (BC, 120 mg/kg diet, daily) was evaluated during diethylnitrosamine (DEN, 200 mg/kg body weight)-induced hepatocarcinogenesis in male Sprague-Dawley rats. BC treatment was carried out throughout the study, before initiation or selection/promotion phase of hepatocarcinogenesis in a defined experimental protocol. In red blood cells (RBC) and microsomal fractions from hepatic nodular and non-nodular surrounding parenchyma, the enzymatic lipid peroxidation increased significantly by more than 3-fold, 9- to 10-fold and 4- to 7-fold respectively 18 weeks following initiation by DEN as compared to normal control animals. RBC membrane protein damage was estimated by alanine release and was found to increase more than 5-fold in the same time period in DEN control rats. A decrease in hepatic cytosolic and microsomal glucose-6-phosphatase activities was observed, whereas the activities of the oxygen-derived free-radical scavenger enzymes, like cytosolic catalase and superoxide dismutase, were shown to increase significantly at the same time point. However, BC exposure in the different phases to hepatocarcinogenesis substantially changed all the above parameters in limiting the action of DEN. Results showed that the most significant beneficial effect of BC during hepatocarcinogenesis was exerted mainly in long term continuous and/or the initiation phase of carcinogenicity, rather than in the selection/promotion phase. Moreover, the volumetric and numerical densities of the preneoplastic lesions were all appreciably reduced by exposure to BC. We conclude that long term intake of BC could reduce cancer risk by preventing hepatic lipid peroxidation and RBC membrane protein damage due to its antioxidant actions.
authors.affiliation: Department of Pharmaceutical Technology, Jadavpur University, Calcutta, India.
authors.forename: A
authors.initials: A
authors.lastname: Sarkar
authors.forename: A
authors.initials: A
authors.lastname: Bishayee
authors.forename: M
authors.initials: M
authors.lastname: Chatterjee
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D002273:Carcinogens; D002338:Carotenoids / Q000494:pharmacology* / Q000627:therapeutic use; D003600:Cytosol / Q000737:chemistry; D004052:Diethylnitrosamine; D004910:Erythrocyte Membrane / Q000187:drug effects*; D005609:Free Radicals; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D006965:Hyperplasia; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000097:blood / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D008563:Membrane Lipids / Q000378:metabolism*; D008862:Microsomes, Liver / Q000737:chemistry; D009363:Neoplasm Proteins / Q000378:metabolism; D018384:Oxidative Stress; D011230:Precancerous Conditions / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D011355:Prodrugs; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D019207:beta Carotene
chemical_list: D016588:Anticarcinogenic Agents; D000975:Antioxidants; D002273:Carcinogens; D005609:Free Radicals; D008563:Membrane Lipids; D009363:Neoplasm Proteins; D011355:Prodrugs; D017382:Reactive Oxygen Species; D019207:beta Carotene; D002338:Carotenoids; D004052:Diethylnitrosamine; D005952:Glucose-6-Phosphatase