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Research ArticleArticle

SLOW ELIMINATION OF NONYLPHENOL FROM RAT INTESTINE

Tomo Daidoji, Mihoko Ozawa, Hirokazu Sakamoto, Toshiro Sako, Hiroki Inoue, Ryo Kurihara, Shinya Hashimoto and Hiroshi Yokota
Drug Metabolism and Disposition January 2006, 34 (1) 184-190; DOI: https://doi.org/10.1124/dmd.105.007229
Tomo Daidoji
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Mihoko Ozawa
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Hirokazu Sakamoto
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Toshiro Sako
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Hiroki Inoue
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Ryo Kurihara
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Shinya Hashimoto
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Hiroshi Yokota
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Abstract

Nonylphenol, a possible endocrine disrupter, tends to persist in rat liver tissue after detoxification as a glucuronide conjugate by UDP-glucuronosyltransferase 2B1 expressed in the liver. In the intestine, however, the metabolism and dynamics of nonylphenol remain to be elucidated. The objectives of this study were to clarify the metabolism and excretion of nonylphenol having a long alkyl chain in the first barrier intestine and to estimate whether the nonylphenol alkyl chain governs the speed of excretion from intestinal tissue. Organ tissue glucuronidation activity toward alkylphenols (C2, C9) was investigated using microsomes prepared from intestinal tissue. To elucidate the elimination pathway of alkylphenols (C2, C4, C6, C9), a perfusion study was conducted on everted intestine. After oral administration (5 mg) of alkylphenols (C2, C9) to rats, gastrointestinal contents and related organ tissues (gastrointestinal tissue, liver, and kidney), blood, and urine were analyzed for alkylphenols (C2, C9) and glucuronides. The intestine showed strong glucuronidation activity toward alkylphenols (C2, C9). In everted intestinal assay, nonylphenol was glucuronidated within the intestinal wall, as was the case for other alkylphenols (C2, C4, C6), but nonylphenol-glucuronide was not excreted from intestinal tissue. Orally administered nonylphenol remained for long periods in gastrointestinal tissue as both the parent compound and glucuronide. The present study confirmed that intestinal tissue possesses an alkylphenol elimination system using UDP-glucuronosyltransferase; however, this system is impaired by the marginal transport of alkylphenol-glucuronide possessing long alkyl chain, such as nonylphenol.

Footnotes

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

  • doi:10.1124/dmd.105.007229.

  • ABBREVIATIONS: UGT, UDP-glucuronosyltransferase; HPLC, high-performance liquid chromatography; MRP, multidrug resistance-associated protein; bisphenol A, 2,2-bis[4-hydroxyphenyl]propane.

    • Received September 5, 2005.
    • Accepted October 19, 2005.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 34 (1)
Drug Metabolism and Disposition
Vol. 34, Issue 1
1 Jan 2006
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Research ArticleArticle

SLOW ELIMINATION OF NONYLPHENOL FROM RAT INTESTINE

Tomo Daidoji, Mihoko Ozawa, Hirokazu Sakamoto, Toshiro Sako, Hiroki Inoue, Ryo Kurihara, Shinya Hashimoto and Hiroshi Yokota
Drug Metabolism and Disposition January 1, 2006, 34 (1) 184-190; DOI: https://doi.org/10.1124/dmd.105.007229

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Research ArticleArticle

SLOW ELIMINATION OF NONYLPHENOL FROM RAT INTESTINE

Tomo Daidoji, Mihoko Ozawa, Hirokazu Sakamoto, Toshiro Sako, Hiroki Inoue, Ryo Kurihara, Shinya Hashimoto and Hiroshi Yokota
Drug Metabolism and Disposition January 1, 2006, 34 (1) 184-190; DOI: https://doi.org/10.1124/dmd.105.007229
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