title: Effects of pregnenolone-16alpha-carbonitrile on vitamin E status and protein levels of antioxidant enzymes in male rats fed a vitamin E-supplemented diet.
abstract: The aim of this study was to evaluate the effects of the administration of pregnenolone-16alpha-carbonitrile (PCN), an inducer of the cytochrome P450 3A gene in rats, on vitamin E status and antioxidant enzyme protein levels in rats fed a vitamin E-supplemented diet. Two groups of male Wistar rats were fed for 3 weeks with a basal diet containing 50 ppm of alpha-tocopherol or the same diet containing 10 times more alpha-tocopherol. In the final 3 days, each group was divided into two subgroups which were given a single daily intraperitoneal injection of PCN at 75 mg/kg (groups PCN and PCN+VE) or DMSO (groups DS and DS+VE). PCN treatment alone significantly reduced the alpha-tocopherol content of the liver and plasma and this effect was prevented by supplementation with 10-fold more alpha-tocopherol. alpha-Tocopherol levels in the kidneys, lung, heart, and testes were significantly higher in both vitamin E-supplemented groups than in the control groups. TBARS levels in the liver and lung were significantly increased in both PCN-treated groups, as shown by two-way ANOVA analysis. PCN also caused a significant reduction in protein levels of catalase and glutathione peroxidase (GPx) in both groups. Dietary vitamin E supplementation caused a decrease in liver protein levels of GPx and superoxide dismutase, but not catalase, in both groups and protected against PCN-induced lipid peroxidation, which was caused by CYP3A induction and a reduction in antioxidant enzyme levels.
authors.affiliation: Department of Health and Nutrition, Chia-Nan University of Pharmacy and Science, 60 Erh-Jen Road Sec. 1, Jen-Te Hsiang, Tainan, Taiwan. mei@mail.chna.edu.tw
authors.forename: Huey-Mei
authors.initials: HM
authors.lastname: Shaw
authors.forename: Wan-Hsuan
authors.initials: WH
authors.lastname: Chen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000378:metabolism; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A; D019587:Dietary Supplements; D005979:Glutathione Peroxidase; D006801:Humans; D015227:Lipid Peroxidation; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008862:Microsomes, Liver / Q000201:enzymology; D009929:Organ Size; D011285:Pregnenolone Carbonitrile / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000097:blood
chemical_list: D000975:Antioxidants; D008565:Membrane Proteins; D017392:Thiobarbituric Acid Reactive Substances; D011285:Pregnenolone Carbonitrile; D002374:Catalase; D005979:Glutathione Peroxidase; D001189:Aryl Hydrocarbon Hydroxylases; C465260:Cyp3a2 protein, rat; C465138:Cyp3a23-3a1 protein, rat; D051544:Cytochrome P-450 CYP3A; D013482:Superoxide Dismutase; D024502:alpha-Tocopherol