Document Detail


The therapeutic effects of ursodeoxycholic acid as an anti-apoptotic agent.
MedLine Citation:
PMID:  11772248     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The dihydroxy bile acid, ursodeoxycholic acid (UDCA), has been in widespread clinical use in the Western world since the mid 1980s, when it was initially used for gallstone dissolution [1,2] and subsequently for the treatment of chronic cholestatic liver diseases [3,4]. Many clinical trials of UDCA in a variety of cholestatic disorders established biochemical and clinical improvements, and most importantly showed a significant prolongation of transplant-free survival after four years of treatment with UDCA in patients with primary biliary cirrhosis [5]. Despite its clinical efficacy, the precise mechanism(s) by which UDCA improves liver function during cholestasis is still a matter of debate [6]. It was initially considered that the choleretic effect of UDCA, coupled with its ability to cause a marked shift in the composition of the bile acid pool towards hydrophilicity, accounted for its mechanism of action. In recent years, however, it has become evident that UDCA and its conjugated derivatives are capable of exerting direct effects at the cellular, subcellular, and molecular levels by stabilising cell membranes, affecting signal transduction pathways, and regulating immune responses. In addition, we have shown that UDCA plays a unique role in modulating the apoptotic threshold in both hepatic and non-hepatic cells [7-10]. The purpose of this article is to examine the mechanism(s) by which UDCA prevents apoptotic cell death associated with cholestasis. In addition, we will also review a potentially novel and, heretofore, unrecognised role of UDCA as a therapeutic agent in the treatment of non-liver diseases associated with increased levels of apoptosis as a pathogenesis of the disorder.
Authors:
C M Rodrigues; C J Steer
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Expert opinion on investigational drugs     Volume:  10     ISSN:  1354-3784     ISO Abbreviation:  Expert Opin Investig Drugs     Publication Date:  2001 Jul 
Date Detail:
Created Date:  2002-01-04     Completed Date:  2002-03-11     Revised Date:  2005-11-16    
Medline Journal Info:
Nlm Unique ID:  9434197     Medline TA:  Expert Opin Investig Drugs     Country:  England    
Other Details:
Languages:  eng     Pagination:  1243-53     Citation Subset:  IM    
Affiliation:
Centro de Patogénese Molecular, Faculdade de Farmácia, University of Lisbon, Av. Forças Armadas, 1600-083 Lisbon, Portugal. cmprodrigues@ff.ul.pt
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects*
Bile Acids and Salts / biosynthesis
Cholestasis / drug therapy,  metabolism
Humans
Mitochondria / drug effects,  metabolism
Neurodegenerative Diseases / drug therapy,  metabolism
Neuroprotective Agents / pharmacology,  therapeutic use
Ursodeoxycholic Acid / pharmacology*,  therapeutic use
Chemical
Reg. No./Substance:
0/Bile Acids and Salts; 0/Neuroprotective Agents; 128-13-2/Ursodeoxycholic Acid

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