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Drug Metabolism and Disposition Fast Forward
First published on October 21, 2005; DOI: 10.1124/dmd.105.007229

0090-9556/06/3401-184-190$20.00
DMD 34:184-190, 2006

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SLOW ELIMINATION OF NONYLPHENOL FROM RAT INTESTINE

Tomo Daidoji, Mihoko Ozawa, Hirokazu Sakamoto, Toshiro Sako, Hiroki Inoue, Ryo Kurihara, Shinya Hashimoto, and Hiroshi Yokota

Department of Veterinary Biochemistry (T.D., M.O., H.S., H.Y.), Veterinary Pathology (T.S.), School of Veterinary Medicine, and Laboratory of Environmental Biochemistry, Department of Biosphere and Environmental Sciences (H.I.), Rakuno Gakuen University, Hokkaido, Japan; and Institute for Environmental Sciences, University of Shizuoka, Shizuoka, Japan (R.K., S.H.)

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.

Address correspondence to: Hiroshi Yokota, Department of Veterinary Biochemistry, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069, Japan. E-mail: h-yokota{at}rakuno.ac.jp






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