title: Suppression of diethylnitrosamine and 2-acetylaminofluorene-induced hepatocarcinogenesis in rats by tocotrienol-rich fraction isolated from rice bran oil.
abstract: The anticancer efficacy of tocotrienol-rich fraction (TRF) was evaluated during diethylnitrosamine (DEN)/2-acetylaminofluorene (AAF)-induced hepatocarcinogenesis in male Sprague-Dawley rats. TRF treatment was carried out for 6 months, and was started 2 weeks before initiation phase of hepatocarcinogenesis. Morphological examination of the livers from DEN/AAF rats showed numerous off-white patches and few small nodules, which were significantly reduced by TRF treatment. Cytotoxic damage by DEN/AAF was estimated by alkaline phosphatase (ALP) release into the plasma from the cell membranes. DEN/AAF caused a twofold increase in the activity of ALP in plasma as compared with normal control rats, and this increase was prevented significantly by TRF treatment. We observed an increase of 79% in liver ALP activity in DEN/AAF rats, which was further increased by another 48% after the administration of TRF. Hepatic activity of glutathione S-transferase (GST) was also increased (3.5-fold) during the induction of hepatic carcinogenesis. Lipid peroxidation and low-density lipoprotein (LDL) oxidation increased threefold following initiation by DEN/AAF as compared with normal control rats. However, TRF treatment to DEN/AAF-treated rats substantially decreased (62-66%) the above parameters and thus limited the action of DEN/AAF. We conclude that long-term intake of TRF could reduce cancer risk by preventing hepatic lipid peroxidation and protein oxidation damage due to its antioxidant actions.
authors.affiliation: Anatomy & Cell Biology, Box #5, SUNY Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY-11203, USA. jahangir.iqbal@downstate.edu
authors.forename: J
authors.initials: J
authors.lastname: Iqbal
authors.forename: M
authors.initials: M
authors.lastname: Minhajuddin
authors.forename: Z H
authors.initials: ZH
authors.lastname: Beg
mesh_terms: D015073:2-Acetylaminofluorene / Q000008:administration & dosage / Q000494:pharmacology; D000477:Alkylating Agents / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000924:Anticholesteremic Agents / Q000737:chemistry*; D000975:Antioxidants / Q000494:pharmacology*; D002273:Carcinogens / Q000008:administration & dosage / Q000494:pharmacology; D018890:Chemoprevention; D004052:Diethylnitrosamine / Q000008:administration & dosage / Q000494:pharmacology; D015227:Lipid Peroxidation; D008113:Liver Neoplasms / Q000517:prevention & control*; D008297:Male; D009374:Neoplasms, Experimental; D018384:Oxidative Stress; D010938:Plant Oils / Q000737:chemistry*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000073879:Rice Bran Oil; D024508:Tocotrienols / Q000494:pharmacology*
chemical_list: D000477:Alkylating Agents; D000924:Anticholesteremic Agents; D000975:Antioxidants; D002273:Carcinogens; D010938:Plant Oils; D011506:Proteins; D024508:Tocotrienols; D004052:Diethylnitrosamine; D015073:2-Acetylaminofluorene; D000073879:Rice Bran Oil