Urinary Elimination of Bile Acid Glucuronides under Severe Cholestatic Situations: Contribution of Hepatic and Renal Glucuronidation Reactions. (11th April 2018)

• Record Type: Journal Article
• Authors: Perreault, Martin; Wunsch, Ewa; Białek, Andrzej; Trottier, Jocelyn; Verreault, Mélanie; Caron, Patrick; Poirier, Guy G.; Milkiewicz, Piotr; Barbier, Olivier
• Other Names: Lapierre Pascal Academic Editor.
• Is Part Of: Canadian journal of gastroenterology & hepatology. Volume 2018(2018)
• Publication Date: 2018-04-11
• Subjects: Digestive organs -- Diseases -- Periodicals; Gastroenterology -- Periodicals; Digestive organs -- Diseases; Gastroenterology; Canada; Digestive System Diseases -- Periodicals; Gastroenterology -- Periodicals; Periodicals; Electronic journals; Fulltext; Internet Resources; Periodicals; 616.3
• DOI: 10.1155/2018/8096314
• Languages: English
• ISSNs: 2291-2789

Abstract

Abstract : Biliary obstruction, a severe cholestatic complication, causes accumulation of toxic bile acids (BAs) in liver cells. Glucuronidation, catalyzed by UDP-glucuronosyltransferase (UGT) enzymes, detoxifies cholestatic BAs. Using liquid chromatography coupled to tandem mass spectrometry, 11 BA glucuronide (-G) species were quantified in prebiliary and postbiliary stenting serum and urine samples from 17 patients with biliary obstruction. Stenting caused glucuronide- and fluid-specific changes in BA-G levels and BA-G/BA metabolic ratios. In vitro glucuronidation assays with human liver and kidney microsomes revealed that even if renal enzymes generally displayed lowerK M values, the two tissues shared similar glucuronidation capacities for BAs. By contrast, major differences between the two tissues were observed when four human BA-conjugating UGTs 1A3, 1A4, 2B4, and 2B7 were analyzed for mRNA and protein levels. Notably, the BA-24G producing UGT1A3 enzyme, abundant in the liver, was not detected in kidney microsomes. In conclusion, the circulating and urinary BA-G profiles are hugely impacted under severe cholestasis. The similar BA-glucuronidating abilities of hepatic and renal extracts suggest that both the liver and kidney may contribute to the urine BA-G pool.