Document Detail


Beneficial effect of ursodeoxycholic acid on alterations induced by cholestasis of pregnancy in bile acid transport across the human placenta.
MedLine Citation:
PMID:  9625319     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND/AIMS: The existence of impairment in bile acid transport across the placenta during intrahepatic cholestasis of pregnancy and the effect of ursodeoxycholic acid treatment (1 g/day) were investigated. METHODS: Kinetic parameters were calculated from experiments carried out on membrane vesicles obtained from basal (TPMb, fetal-facing) and apical (TPMa, maternal-facing) trophoblast plasma membranes. Bile acid uptake was measured using varying concentrations of [14C]-glycocholate and a rapid filtration technique. RESULTS: The maximal velocity of transport (Vmax), the apparent affinity constant (Kt) and the efficiency (Ef) of transport (Vmax/Kt) of the anion:bile acid exchanger located at the TPMb were reduced in intrahepatic cholestasis of pregnancy. Ursodeoxycholic acid induced a reversal of Vmax, Kt and Ef to normal values. Owing to the 3-fold increase in Vmax, with no change in Kt, intrahepatic cholestasis of pregnancy induced an enhancement in Ef of ATP-independent bile acid transport across TPMa. Both Vmax and Ef were restored to normal values by ursodeoxycholic acid. Finally, in ATP-dependent bile acid transport across TPMa, a reduction in the Ef due to an increase in Vmax together with a more pronounced increase in Kt was found. This impairment was also reversed by ursodeoxycholic acid. CONCLUSIONS: These results suggest that placenta bile acid transport systems are impaired in intrahepatic cholestasis of pregnancy. Moreover, together with the confirmed beneficial effect for intrahepatic cholestasis of pregnancy patients, such as the relief of pruritus and the improvement in biochemical markers of cholestasis, ursodeoxycholic acid treatment restores the ability of the placenta to carry out vectorial bile acid transfer.
Authors:
M A Serrano; D Brites; M G Larena; M J Monte; M P Bravo; N Oliveira; J J Marin
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Publication Detail:
Type:  Clinical Trial; Controlled Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of hepatology     Volume:  28     ISSN:  0168-8278     ISO Abbreviation:  J. Hepatol.     Publication Date:  1998 May 
Date Detail:
Created Date:  1998-07-28     Completed Date:  1998-07-28     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  DENMARK    
Other Details:
Languages:  eng     Pagination:  829-39     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Biology, University of Salamanca, Spain.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism
Adult
Bile Acids and Salts / metabolism*
Biological Transport
Cell Membrane / metabolism
Cholagogues and Choleretics / therapeutic use*
Cholestasis, Intrahepatic / blood,  drug therapy*,  metabolism
Female
Fetus / physiology
Glycocholic Acid / metabolism
Humans
Kinetics
Placenta / metabolism*
Pregnancy
Pregnancy Complications / blood,  drug therapy*,  metabolism
Trophoblasts / metabolism
Ursodeoxycholic Acid / therapeutic use*
Chemical
Reg. No./Substance:
0/Bile Acids and Salts; 0/Cholagogues and Choleretics; 128-13-2/Ursodeoxycholic Acid; 475-31-0/Glycocholic Acid; 56-65-5/Adenosine Triphosphate

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


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