title: Functional and ultrastructural features of ethanol/bile salts interaction in the isolated perfused rat liver.
abstract: 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.affiliation: II Department of Gastroenterology, University of Rome La Sapienza, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Alvaro
authors.forename: A
authors.initials: A
authors.lastname: Benedetti
authors.forename: A
authors.initials: A
authors.lastname: Gigliozzi
authors.forename: A
authors.initials: A
authors.lastname: Bini
authors.forename: P
authors.initials: P
authors.lastname: Della Guardia
authors.forename: T
authors.initials: T
authors.lastname: La Rosa
authors.forename: A M
authors.initials: AM
authors.lastname: Jezequel
authors.forename: L
authors.initials: L
authors.lastname: Capocaccia
mesh_terms: D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism / Q000494:pharmacology*; D000431:Ethanol / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D008297:Male; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology; D013656:Taurocholic Acid / Q000494:pharmacology; D013657:Taurodeoxycholic Acid / Q000494:pharmacology
chemical_list: D001647:Bile Acids and Salts; D000431:Ethanol; D013655:Taurochenodeoxycholic Acid; D013657:Taurodeoxycholic Acid; D013656:Taurocholic Acid; C031655:ursodoxicoltaurine; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases