Document Detail


Ursodeoxycholic acid in cholestasis: linking action mechanisms to therapeutic applications.
MedLine Citation:
PMID:  21854363     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
UDCA (ursodeoxycholic acid) is the therapeutic agent most widely used for the treatment of cholestatic hepatopathies. Its use has expanded to other kinds of hepatic diseases, and even to extrahepatic ones. Such versatility is the result of its multiple mechanisms of action. UDCA stabilizes plasma membranes against cytolysis by tensioactive bile acids accumulated in cholestasis. UDCA also halts apoptosis by preventing the formation of mitochondrial pores, membrane recruitment of death receptors and endoplasmic-reticulum stress. In addition, UDCA induces changes in the expression of metabolizing enzymes and transporters that reduce bile acid cytotoxicity and improve renal excretion. Its capability to positively modulate ductular bile flow helps to preserve the integrity of bile ducts. UDCA also prevents the endocytic internalization of canalicular transporters, a common feature in cholestasis. Finally, UDCA has immunomodulatory properties that limit the exacerbated immunological response occurring in autoimmune cholestatic diseases by counteracting the overexpression of MHC antigens and perhaps by limiting the production of cytokines by immunocompetent cells. Owing to this multi-functionality, it is difficult to envisage a substitute for UDCA that combines as many hepatoprotective effects with such efficacy. We predict a long-lasting use of UDCA as the therapeutic agent of choice in cholestasis.
Authors:
Marcelo G Roma; Flavia D Toledo; Andrea C Boaglio; Cecilia L Basiglio; Fernando A Crocenzi; Enrique J Sánchez Pozzi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Clinical science (London, England : 1979)     Volume:  121     ISSN:  1470-8736     ISO Abbreviation:  Clin. Sci.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-08-22     Completed Date:  2011-10-17     Revised Date:  2011-10-20    
Medline Journal Info:
Nlm Unique ID:  7905731     Medline TA:  Clin Sci (Lond)     Country:  England    
Other Details:
Languages:  eng     Pagination:  523-44     Citation Subset:  IM    
Affiliation:
Institute of Experimental Physiology (IFISE-CONICET), Faculty of Biochemical and Pharmacautical Sciences, National University of Rosario, Suipacha 570, S2002LRL Rosario, Argentina. mroma@fbioyf.unr.edu.ar
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects
Bile Acids and Salts / physiology
Bile Canaliculi / drug effects
Cholagogues and Choleretics / pharmacology*,  therapeutic use
Cholestasis / drug therapy*,  pathology,  physiopathology
Humans
Immunologic Factors / pharmacology,  therapeutic use
Mitochondria, Liver / drug effects,  metabolism
Proto-Oncogene Proteins c-bcl-2 / metabolism
Ursodeoxycholic Acid / pharmacology*,  therapeutic use
Chemical
Reg. No./Substance:
0/Bile Acids and Salts; 0/Cholagogues and Choleretics; 0/Immunologic Factors; 0/Proto-Oncogene Proteins c-bcl-2; 128-13-2/Ursodeoxycholic Acid

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