Document Detail

Interactions of combined bile acids on hepatocyte viability: cytoprotection or synergism.
MedLine Citation:
PMID:  11814708     Owner:  NLM     Status:  MEDLINE    
Cholestasis results from hepatocyte dysfunction due to the accumulation of bile acids in the cell, many of which are known to be cytotoxic. Recent evidence implicates competitive antagonism of key cytotoxic responses as the mechanism by which certain therapeutic bile acids might afford cytoprotection against cholestasis. In this work, we compare the relative cytotoxicity of bile acids in terms of dose- and time-dependence. To better elucidate the controversy related to the therapeutic use of ursodeoxycholate (UDCA) in cholestatic patients, we also evaluated the effects of bile acid combinations. Viability of Wistar rat hepatocytes in primary culture was measured by LDH leakage after 12 and 24 h exposure of cells to the various bile acids. All unconjugated bile acids caused a dose-dependent decrease in cell viability. The tauro- and glyco-conjugates of chenodeoxycholate (CDCA) and UDCA were all less toxic than the corresponding unconjugated form. Although relatively non-toxic, UDCA caused synergistic cell killing by lithocholate (LCA), CDCA, glyco-CDCA (GCDC) and tauro-CDCA (TCDC). Glycoursodeoxycholate decreased the toxicity of GCDC, but potentiated the toxicity of unconjugated CDCA and LCA. The tauro-conjugate of UDCA had no significant effect. These data suggest that at cholestatic concentrations, bile acid-induced cell death correlates with the degree of lipophilicity of individual bile acids. However, these results indicate that the reported improvement of biochemical parameters in cholestatic patients treated with UDCA is not due to a direct effect of UDCA on hepatocyte viability. Therefore, any therapeutic effect of UDCA must be secondary to some other process, such as altered membrane transport or nonparenchymal cell function.
Anabela P Rolo; Carlos M Palmeira; Kendall B Wallace
Related Documents :
2387518 - Effects of ursodeoxycholic acid treatment on nutrition and liver function in patients w...
12620498 - Inhibitory effects of ursodeoxycholic acid on the induction of nitric oxide synthase in...
11180878 - Rapid intravenous administration of amino acids prevents biliary sludge induced by tota...
18501688 - The synthesis of mp-cdca conjugates and dissolution kinetics of model cholesterol galls...
21418708 - Iron regulates the uptake of ascorbic acid and the expression of sodium-dependent vitam...
18835178 - (3s)-n-(l-aminoacyl)-1,2,3,4-tetrahydroisoquinolines, a class of novel antithrombotic a...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Toxicology letters     Volume:  126     ISSN:  0378-4274     ISO Abbreviation:  Toxicol. Lett.     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-01-29     Completed Date:  2002-03-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7709027     Medline TA:  Toxicol Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  197-203     Citation Subset:  IM    
Department of Zoology, Center for Neurosciences and Cell Biology of Coimbra, University of Coimbra, 3004-517 Coimbra, Portugal.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Bile Acids and Salts / pharmacology*
Cell Survival / drug effects
Cholestasis / etiology
Dose-Response Relationship, Drug
Drug Synergism
Hepatocytes / cytology,  drug effects*
Rats, Sprague-Dawley
Reg. No./Substance:
0/Bile Acids and Salts

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

Previous Document:  Linoleic acid, cis-epoxyoctadecenoic acids, and dihydroxyoctadecadienoic acids are toxic to Sf-21 ce...
Next Document:  Capillary electrophoresis of phytochemical substances.