Back to Search
Start Over
Urinary Elimination of Bile Acid Glucuronides under Severe Cholestatic Situations: Contribution of Hepatic and Renal Glucuronidation Reactions.
- Source :
-
Canadian journal of gastroenterology & hepatology [Can J Gastroenterol Hepatol] 2018 Apr 11; Vol. 2018, pp. 8096314. Date of Electronic Publication: 2018 Apr 11 (Print Publication: 2018). - Publication Year :
- 2018
-
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 lower K <subscript> M </subscript> 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.
- Subjects :
- Aged
Cholestasis blood
Cholestasis therapy
Female
Glucuronides blood
Glucuronosyltransferase genetics
Humans
Kidney enzymology
Male
Microsomes, Liver enzymology
Middle Aged
Stents
Bile Acids and Salts metabolism
Cholestasis urine
Glucuronides urine
Glucuronosyltransferase metabolism
RNA, Messenger metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2291-2797
- Volume :
- 2018
- Database :
- MEDLINE
- Journal :
- Canadian journal of gastroenterology & hepatology
- Publication Type :
- Academic Journal
- Accession number :
- 29850459
- Full Text :
- https://doi.org/10.1155/2018/8096314