Document Detail


Metabolism and effects on cholestasis of isoursodeoxycholic and ursodeoxycholic acids in bile duct ligated rats.
MedLine Citation:
PMID:  11287121     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Isoursodeoxycholic acid (isoUDCA), the 3 beta-epimer of ursodeoxycholic acid (UDCA), may have pharmaceutical potential because of its similar hydrophilicity and in vitro cytoprotection as compared with UDCA. We compared metabolism and effects on cholestasis of UDCA and isoUDCA in experimental cholestasis in rats. Cholestasis was induced by bile duct ligation. For bile flow and biliary bile acid analysis, UDCA or isoUDCA were infused intraduodenally. For the study of chronic effects, chow was supplemented with 2.5 g/kg UDCA or isoUDCA for 3 weeks. Sham-operated animals served as controls. IsoUDCA became completely converted to UDCA in the liver. Choleresis and biliary bile acids were the same after the intraduodenal administration of either compound. Oral administration of UDCA or isoUDCA significantly improved liver biochemistry but not clinical and histological parameters in chronic cholestasis. The decrease of serum cholic acid in control animals was more pronounced after isoUDCA (-93%) than after UDCA (-76%). Only after UDCA, this decrease was compensated by increases of UDCA, beta-muricholic acid (MCA), and Delta(22)-beta-MCA. Our results show that isoUDCA has the same effect on choleresis and liver biochemistry as UDCA. IsoUDCA features pro-drug characteristics of UDCA and causes compared to the latter lower serum bile acid concentrations in non-cholestatic animals.
Authors:
E Purucker; H U Marschall; R Winograd; S Matern
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1526     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2001 Apr 
Date Detail:
Created Date:  2001-04-05     Completed Date:  2001-05-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  44-52     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine III, Medical Faculty, Aachen University of Technology, Germany. epurucker@post.klinikum.rwth-aachen.de
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MeSH Terms
Descriptor/Qualifier:
Animals
Bile / metabolism
Bile Acids and Salts / blood,  urine
Bile Ducts / physiology*,  surgery
Body Weight
Cholestasis / metabolism*
Cholic Acids / analysis
Eating
Ligation
Liver / drug effects,  metabolism
Liver Function Tests
Male
Rats
Rats, Sprague-Dawley
Ursodeoxycholic Acid / analogs & derivatives*,  metabolism,  pharmacology*
Chemical
Reg. No./Substance:
0/Bile Acids and Salts; 0/Cholic Acids; 128-13-2/Ursodeoxycholic Acid; 39016-49-4/muricholic acid; 78919-26-3/isoursodeoxycholic acid

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


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