Document Detail


Ursodeoxycholic acid and bile-acid mimetics as therapeutic agents for cholestatic liver diseases: An overview of their mechanisms of action.
MedLine Citation:
PMID:  23141891     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Chronic cholestasis and liver inflammation are the two main pathophysiological components of the two major classes of disease - primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) - leading to bile duct destruction and ultimately to cirrhosis and liver failure. Ursodeoxycholic acid (UDCA), initially introduced as a therapeutic approach to counteract the cholestatic components to PBC and PSC, was subsequently shown to exhibit unexpected anti-inflammatory and immunomodulatoty properties. The use of farnesoid X receptor (FXR) and TGR5 agonists in various animal models have confirmed early observations indicating that bile acids are not only toxicants and inflammagens, but also repressors of innate and adaptive immunity. Obeticholic acid is a bile-acid mimetic, with no toxic or inflammagen behavior, that strongly activates FXR to combat the toxic effects of high concentrations of bile acid. Because UDCA is not an FXR agonist, its combination with obeticholic acid could be a promising tool for the treatment of PBC and PSC. In this overview, the biological properties of UDCA, NorUDCA and FXR agonists are highlighted, as well as their overlapping mechanisms of action in inflammatory biliary disorders.
Authors:
Raoul Poupon
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Clinics and research in hepatology and gastroenterology     Volume:  36 Suppl 1     ISSN:  2210-741X     ISO Abbreviation:  Clin Res Hepatol Gastroenterol     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-11-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101553659     Medline TA:  Clin Res Hepatol Gastroenterol     Country:  France    
Other Details:
Languages:  eng     Pagination:  S3-S12     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Masson SAS. All rights reserved.
Affiliation:
Service d'Hépatologie et Centre de Référence des maladies inflammatoires des voies biliaires, Hôpital Saint-Antoine, AP-HP, 184, rue du Faubourg Saint-Antoine, 75571 Paris cedex 12, France; UPMC University Paris 06, INSERM, UMR-S 938, Paris, France. Electronic address: Raoul.poupon@sat.aphp.fr.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Progressive familial intrahepatic cholestasis.
Next Document:  Low phospholipid-associated cholestasis and cholelithiasis.