期刊
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
卷 20, 期 6, 页码 469-476出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2008.05.007
关键词
alpha-tocopherol; Cytochrome P450; Xenobiotic metabolism; MDR1; Sulfotransferase; Glutathione S-transferase
资金
- NIH [ES011985]
- USDA [NRI 2003-009515]
- Clinical Nutritional Research Unit
- Center for Human Nutritional Research, University of California, and Philip Morris USA
- [DK 067930]
Hepatic proteins involved in xenobiotic pathways (Phases I, II and III) are responsible for the metabolism and disposition of endogenous and exogenous compounds including dietary phytochemicals. To test the hypothesis that elevated alpha-tocopherol intakes alter gene expression of hepatic xenobiotic pathways, mice were fed diets supplemented with either 1000 IU (+E) or 35 IU (E) all-rac-alpha-tocopheryl acetate for 4 months; liver RNA was isolated, and gene expression was determined using both whole genome microarray and real-time quantitative polymerase chain reaction analyses. Hepatic a-tocopherol (173 +/- 18 vs. 21 +/- 1 nmol/g, mean +/- S.E.) and its metabolite (2,5,7,8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxychroman, 0.232 +/- 0.046 vs. 0.031 +/- 0.019 nmol/g) concentrations were approximately eightfold higher following the +E dietary treatment. In +E relative to E mice, gene expression of Phase I enzymes, P450 oxidoreductase and cytochrome P450 3a11 increased 1.6- and 4.0-fold, respectively; two Phase II genes, sulfotransferase 2a and glutathione S-transferase mu 3, increased 10.8- and 1.9-fold respectively, and a Phase III biliary transporter, Abcb1a, doubled. Thus, consumption of high-level dietary alpha-tocopherol simultaneously coordinated Phase I, II and III gene expression. These data demonstrate that increased hepatic alpha-tocopherol modulates its own concentrations through increasing xenobiotic metabolism, a process that may alter metabolism of other foreign compounds, such as therapeutic drugs and phytochemicals, in humans. (C) 2009 Elsevier Inc. All rights reserved.
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