| The therapeutic effects of ursodeoxycholic acid as an anti-apoptotic agent. | |
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MedLine Citation:
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PMID: 11772248 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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C M Rodrigues; C J Steer |
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Publication Detail:
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Type: Journal Article; Review |
Journal Detail:
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Title: Expert opinion on investigational drugs Volume: 10 ISSN: 1354-3784 ISO Abbreviation: Expert Opin Investig Drugs Publication Date: 2001 Jul |
Date Detail:
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Created Date: 2002-01-04 Completed Date: 2002-03-11 Revised Date: 2005-11-16 |
Medline Journal Info:
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Nlm Unique ID: 9434197 Medline TA: Expert Opin Investig Drugs Country: England |
Other Details:
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Languages: eng Pagination: 1243-53 Citation Subset: IM |
Affiliation:
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Centro de Patogénese Molecular, Faculdade de Farmácia, University of Lisbon, Av. Forças Armadas, 1600-083 Lisbon, Portugal. cmprodrigues@ff.ul.pt |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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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:
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0/Bile Acids and Salts; 0/Neuroprotective Agents; 128-13-2/Ursodeoxycholic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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