Document Detail


Functional and ultrastructural features of ethanol/bile salts interaction in the isolated perfused rat liver.
MedLine Citation:
PMID:  7705787     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We investigated whether bile salts (BS) with different hydrophobic-hydrophilic properties interact with ethanol on bile secretion, enzyme (aspartate transaminase [AST], lactate dehydrogenase [LDH]) release in the perfusate, liver ultrastructure, and vesicular exocytosis in the isolated perfused rat liver. Ethanol (0.1 or 1%) promoted a rapid decrease of bile flow and BS secretion in livers perfused with taurocholate (TCA), the physiologic BS in the rat (-28% decrease of baseline values with 0.1% and -34% with 1% ethanol). The inhibitory effect of ethanol on bile flow and BS secretion was significantly (P < .02) attenuated by perfusing liver with the hydrophilic BS, tauroursodeoxycholate (TUDCA), and it was exacerbated (P < .02) by perfusion with the hydrophobic BS, taurodeoxycholate (TDCA). The release of AST and LDH in the perfusate was unaffected by 0.1% ethanol, but increased threefold to fivefold by 1% ethanol in TCA-perfused livers. This cytolitic effect of ethanol was not observed in TUDCA-perfused livers, but it was enhanced (P < .03) by perfusion with TDCA. No ultrastructural abnormalities were found in either TCA- or TUDCA-perfused livers, with or without 1% ethanol. Only minimal changes were found in livers perfused with TDCA alone, but, in the presence of TDCA, 1% ethanol induces marked mitochondrial damage. The biliary excretion of the fluid phase marker horseradish peroxidase was inhibited by ethanol, an effect reversed by TUDCA (P < .02) and exacerbated by TDCA (P < .04). In conclusion, this study demonstrates that hydrophilic BS such as TUDCA counteract the inhibitory effect of ethanol on bile secretion and vesicular exocytosis as well as the ethanol-induced cytolitic effect in the isolated perfused rat liver. In the presence of hydrophobic BS such as TDCA, the exposure to ethanol promotes a marked inhibition of bile secretion and vesicular exocytosis as well as prominent mitochondrial damage.
Authors:
D Alvaro; A Benedetti; A Gigliozzi; A Bini; P Della Guardia; T La Rosa; A M Jezequel; L Capocaccia
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  21     ISSN:  0270-9139     ISO Abbreviation:  Hepatology     Publication Date:  1995 Apr 
Date Detail:
Created Date:  1995-05-09     Completed Date:  1995-05-09     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1120-9     Citation Subset:  IM    
Affiliation:
II Department of Gastroenterology, University of Rome La Sapienza, Italy.
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MeSH Terms
Descriptor/Qualifier:
Animals
Aspartate Aminotransferases / secretion
Bile / drug effects,  secretion
Bile Acids and Salts / pharmacology*,  secretion
Ethanol / toxicity*
L-Lactate Dehydrogenase / secretion
Liver / drug effects*,  physiology,  ultrastructure
Male
Perfusion
Rats
Rats, Wistar
Taurochenodeoxycholic Acid / pharmacology
Taurocholic Acid / pharmacology
Taurodeoxycholic Acid / pharmacology
Chemical
Reg. No./Substance:
0/Bile Acids and Salts; 14605-22-2/tauroursodeoxycholic acid; 516-35-8/Taurochenodeoxycholic Acid; 516-50-7/Taurodeoxycholic Acid; 64-17-5/Ethanol; 81-24-3/Taurocholic Acid; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 2.6.1.1/Aspartate Aminotransferases

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