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0090-9556/03/3108-993-998$20.00
DMD 31:993-998, 2003

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GLUCURONIDATION AND EXCRETION OF NONYLPHENOL IN PERFUSED RAT LIVER

Tomo Daidoji, Hiroki Inoue, Seiyu Kato, and Hiroshi Yokota

Departments of Veterinary Biochemistry (T.D., H.Y.) and Veterinary Physiology (H.I., S.K.), School of Veterinary Medicine, Rakuno Gakuen University, Hokkaido, Japan

Nonylphenol, an environmental estrogenic chemical, is reported to have adverse effects on the reproductive organs of animals. In this study, the metabolism of nonylphenol and that of other alkylphenols in the rat liver was investigated using liver perfusion. Alkylphenols (nonylphenol, hexylphenol, butylphenol, and ethylphenol) were glucuronidated by rat liver microsomes. Nonylphenol was found to be conjugated with glucuronic acid by an isoform of UDP-glucuronosyltransferase, UGT2B1, expressed in yeast AH22 cells. However, when nonylphenol was perfused into rat liver in situ, it was difficult for free nonylphenol and conjugated metabolite to be excreted into the bile or vein, and most of the perfused nonylphenol remained free and as a glucuronide conjugate in the liver tissue, even after 1 h of perfusion. After 1 h of perfusion of the other alkylphenols, most of them were excreted into the bile as glucuronides. Ethylphenol, which has the shortest alkyl chain, was excreted rapidly into both the bile and vein; however, the excretion rates of alkylphenols having longer alkyl chains tended to be slow. MRP-2-deficient Eisai hyperbilirubinemic rats could not secrete alkylphenol-glucuronides into the bile, indicating that alkylphenol-glucuronides are transported by MRP-2 to the bile in normal Sprague-Dawley rats. The results indicate that the kinetics of excretion of alkylphenol-glucuronides into the bile or vein depends on the length of alkyl chain and suggest that nonylphenol-glucuronide formed in the liver cannot be transported by MRP-2.

Address correspondence to: Hiroshi Yokota, Department of Veterinary Biochemistry, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido, 069-8501 Japan. E-mail: h-yokota{at}rakuno.ac.jp




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