title: Increased UDP-glucuronosyltransferase activity and UDP-glucuronic acid concentration in the small intestine of butylated hydroxyanisole-treated mice.
abstract: Butylated hydroxyanisole (BHA) has been shown to decrease the toxicological and carcinogenic potential of a variety of chemicals. One possible mechanism for chemoprotection is that BHA increases intestinal UDP-glucuronosyltransferase activity and thereby enhances the elimination of the toxicants. Given that oral ingestion is a major route of xenobiotic exposure, we have investigated the actions of BHA on the glucuronidation capacity in the upper small intestine of female mice. Ingestion of high dosages of BHA (600-800 mg/kg/day) for 10 days produced a significant increase in in vitro microsomal acetaminophen glucuronidation but not in diethylstilbestrol conjugation. Furthermore, the concentration of UDP-glucuronic acid, the co-substrate required for glucuronidation reactions, was increased almost 2-fold in small intestine. Ingestion of BHA also increased UDP-glucose concentration and UDP-glucose dehydrogenase activities approximately 2-fold. These findings show that BHA ingestion increases intestinal glucuronidation capacity and suggest that BHA may enhance the intestinal first-pass biotransformation of xenobiotics.
authors.forename: J J
authors.initials: JJ
authors.lastname: Hjelle
authors.forename: G A
authors.initials: GA
authors.lastname: Hazelton
authors.forename: C D
authors.initials: CD
authors.lastname: Klaassen
mesh_terms: D000082:Acetaminophen / Q000378:metabolism; D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D002083:Butylated Hydroxyanisole / Q000494:pharmacology*; D004054:Diethylstilbestrol / Q000378:metabolism; D005260:Female; D014453:Glucuronosyltransferase / Q000378:metabolism*; D007421:Intestine, Small / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D014535:Uridine Diphosphate Glucuronic Acid / Q000378:metabolism*; D014539:Uridine Diphosphate Sugars / Q000378:metabolism*
chemical_list: D000840:Anisoles; D014539:Uridine Diphosphate Sugars; D002083:Butylated Hydroxyanisole; D014535:Uridine Diphosphate Glucuronic Acid; D000082:Acetaminophen; D004054:Diethylstilbestrol; D014453:Glucuronosyltransferase