SLOW ELIMINATION OF NONYLPHENOL FROM RAT INTESTINE
- 21 October 2005
- journal article
- research article
- Published by American Society for Pharmacology & Experimental Therapeutics (ASPET)
- Vol. 34 (1), 184-190
- https://doi.org/10.1124/dmd.105.007229
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.Keywords
This publication has 22 references indexed in Scilit:
- GLUCURONIDATION AND EXCRETION OF NONYLPHENOL IN PERFUSED RAT LIVERDrug Metabolism and Disposition, 2003
- Male-specific suppression of hepatic microsomal UDP-glucuronosyl transferase activities toward sex hormones in the adult male rat administered bisphenol ABiochemical Journal, 2002
- Relative Enzymatic Activity, Protein Stability, and Tissue Distribution of Human Steroid-Metabolizing UGT2B Subfamily MembersEndocrinology, 2001
- Disruption of the reproductive system and reproductive performance by administration of nonyiphenol to newborn ratsHuman & Experimental Toxicology, 2000
- 1-Naphthol β-D-glucuronide formed intraluminally in rat small intestine mucosa and absorbed into the colonLife Sciences, 1999
- Hepatobiliary secretion of organic compounds; molecular mechanisms of membrane transportBiochimica et Biophysica Acta (BBA) - Reviews on Biomembranes, 1995
- Environmentally persistent alkylphenolic compounds are estrogenicEndocrinology, 1994
- p-Nonyl-phenol: an estrogenic xenobiotic released from "modified" polystyrene.Environmental Health Perspectives, 1991
- Purification of Rat‐Liver Microsomal UDP‐glucuronyltransferaseEuropean Journal of Biochemistry, 1979
- Intestinal Bacteria And The Hydrolysis Of Glycosidic BondsJournal of Medical Microbiology, 1971