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Cytochrome P450-Dependent Metabolism of Vitamin E Isoforms is a Critical Determinant of Their Tissue Concentrations in Rats

  • Original Article
  • Nutrition
  • Published:
Lipids

Abstract

The aim of this study was to clarify the contribution of cytochrome P450 (CYP)-dependent metabolism of vitamin E isoforms to their tissue concentrations. We studied the effect of ketoconazole, a potent inhibitor of CYP-dependent vitamin E metabolism in cultured cells, on vitamin E concentration in rats. Vitamin E-deficient rats fed a vitamin E-free diet for 4 weeks were administered by oral gavage a vitamin E-free emulsion, an emulsion containing α-tocopherol, γ-tocopherol or a tocotrienol mixture with or without ketoconazole. α-Tocopherol was detected in the serum and various tissues of the vitamin E-deficient rats, but γ-tocopherol, α- and γ-tocotrienol were not detected. Ketoconazole decreased urinary excretion of 2,5,7,8-tetramethyl-2(2′-carboxyethyl)-6-hydroxychroman after α-tocopherol or a tocotrienol mixture administration, and that of 2,7,8-trimethyl-2(2′-carboxyethyl)-6-hydroxychroman (γ-CEHC) after γ-tocopherol or a tocotrienol mixture administration. The γ-tocopherol, α- and γ-tocotrienol concentrations in the serum and various tissues at 24 h after their administration were elevated by ketoconazole, while the α-tocopherol concentration was not affected. The γ-tocopherol or γ-tocotrienol concentration in the jejunum at 3 h after each administration was also elevated by ketoconazole. In addition, significant amount of γ-CEHC was in the jejunum at 3 h after γ-tocopherol or γ-tocotrienol administration, and ketoconazole inhibited γ-tocopherol metabolism to γ-CEHC in the jejunum. These results showed that CYP-dependent metabolism of γ-tocopherol and tocotrienol is a critical determinant of their concentrations in the serum and tissues. The data also suggest that some amount of dietary vitamin E isoform is metabolized by a CYP-mediated pathway in the intestine during absorption.

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Abbreviations

α-CEHC:

2,5,7,8-Tetramethyl-2(2′-carboxyethyl)-6-hydroxychroman

γ-CEHC:

2,7,8-Trimethyl-2(2′-carboxyethyl)-6-hydroxychroman

CYP:

Cytochrome P450

α-TTP:

α-Tocopherol transfer protein

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Acknowledgments

This study was supported in part by Grant-in Aid for Scientific Research 15680018 from Japan Society for the Promotion of Science, Japan. The authors are grateful to Eisai Food & Chemical for their contribution of vitamin E isoforms and their metabolites, and to Hiroaki Oda for his assistance with animal experimentation.

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Authors and Affiliations

  1. Department of Nutritional Sciences, Nagoya University of Arts and Sciences, 57 Takenoyama, Iwasaki, Nissin, 470-0196, Japan

    Chisato Abe, Tomono Uchida, Moeka Ohta, Tomio Ichikawa & Saiko Ikeda

  2. Department of Food and Nutrition, Sugiyama Jogakuen University, Nagoya, 464-8662, Japan

    Kanae Yamashita

Authors
  1. Chisato Abe
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  2. Tomono Uchida
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  3. Moeka Ohta
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  4. Tomio Ichikawa
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  5. Kanae Yamashita
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  6. Saiko Ikeda
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Corresponding author

Correspondence to Saiko Ikeda.

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Abe, C., Uchida, T., Ohta, M. et al. Cytochrome P450-Dependent Metabolism of Vitamin E Isoforms is a Critical Determinant of Their Tissue Concentrations in Rats. Lipids 42, 637–645 (2007). https://doi.org/10.1007/s11745-007-3064-2

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  • DOI: https://doi.org/10.1007/s11745-007-3064-2

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