Document Detail

Tauroursodeoxycholate and S-adenosyl-L-methionine exert an additive ameliorating effect on taurolithocholate-induced cholestasis: a study in isolated rat hepatocyte couplets.
MedLine Citation:
PMID:  9918924     Owner:  NLM     Status:  MEDLINE    
The monohydroxy bile acid, taurolithocholate (TLC), causes cholestasis in vivo and in isolated perfused livers. It is also cholestatic in vitro and, in this study using isolated rat hepatocyte couplets, causes a reduction of the accumulation of (fluorescent) bile acid in the canalicular vacuoles (cVA) of this polarized cell preparation. The hepatoprotective bile acid, tauroursodeoxycholate (TUDCA), partially protects against the action of TLC when added at the same time. It also partially reverses the cholestatic effect if added after the cells have been exposed to TLC. A second hepatoprotective compound, S-adenosyl-L-methionine (SAMe) also not only partially protects against the action of TLC when added at the same time, but it too is able to partially reverse the cholestatic effect. Neither hepatoprotective agent is fully effective alone, but their effects are additive. In combination, a full restoration of cVA is observed in moderate cholestasis, but not in severe cholestasis. We discuss briefly some possible mechanisms involved in the additive mode of action of both hepatoprotective compounds. In summary, we show for the first time that SAMe and TUDCA can exert an additive effect in the amelioration of TLC-induced cholestasis in isolated rat hepatocyte couplets. This finding may be of possible clinical relevance.
P Milkiewicz; C O Mills; M G Roma; J Ahmed-Choudhury; E Elias; R Coleman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  29     ISSN:  0270-9139     ISO Abbreviation:  Hepatology     Publication Date:  1999 Feb 
Date Detail:
Created Date:  1999-02-16     Completed Date:  1999-02-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  471-6     Citation Subset:  IM    
Liver and Hepatobiliary Unit, Queen Elizabeth Hospital, Birmingham, UK.
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MeSH Terms
Bile Acids and Salts / metabolism
Bile Canaliculi / ultrastructure
Cholestasis / chemically induced*,  prevention & control
Fluorescent Dyes
Rats, Wistar
S-Adenosylmethionine / pharmacology*
Taurochenodeoxycholic Acid / pharmacology*
Taurolithocholic Acid / toxicity*
Vacuoles / drug effects,  metabolism
Reg. No./Substance:
0/Bile Acids and Salts; 0/Fluorescent Dyes; 14605-22-2/tauroursodeoxycholic acid; 29908-03-0/S-Adenosylmethionine; 516-35-8/Taurochenodeoxycholic Acid; 516-90-5/Taurolithocholic Acid

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

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