Urinary Elimination of Bile Acid Glucuronides Under Severe Cholestatic Situations: Contribution of Hepatic and Renal Glucuronidation Reactions

Overview

Journal Can J Gastroenterol Hepatol

Specialty Gastroenterology

Date 2018 Jun 1

PMID 29850459

Citations 5

Authors

Martin Perreault

Ewa Wunsch

Andrzej Bialek

Jocelyn Trottier

Melanie Verreault

Patrick Caron

Guy G Poirier

Piotr Milkiewicz

Olivier Barbier

Affiliations

Soon will be listed here.

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. glucuronidation assays with human liver and kidney microsomes revealed that even if renal enzymes generally displayed lower 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.

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