title: Effect of high concentrations of bile acids on cultured hepatocytes.
abstract: High concentrations of bile acids have been reported as injurious to hepatocytes. We report the influence of various combinations of bile acids on the liver-specific function of cultured rat hepatocytes. Using 4 bile acids (glycocholate [GC], taurocholate [TC], glycohenodeoxycholate [GCDC], and taurochenodeoxycholate [TCDC]), we obtained 6 bile-acid mixtures, each containing equal amounts of 2 bile acids (total bile acids [TBA], 2 mM). Changes in gluconeogenesis, ureagenesis, DNA contents, medium alanine aminotransferase, and morphologies were compared among the paired bile acid compositions by measuring the C/CDC ratio ([GC + TC]/[GCDC + TCDC]) of each. In terms of their relative impairments of ureagenesis from greatest to least, the acids were GCDC, TCDC, and GC, which was almost the same as TC. When the C/CDC ratio was 0, the values of all parameters measured deteriorated. When the C/CDC ratio was 1 in the presence of 1 mM GCDC, only the rate of ureagenesis was diminished. When the C/CDC ratio was infinite, no hepatocellular injury was observed. GCDC and TCDC, together or separately, showed significant hepatocellular injury when the TBA concentration was 2 mM.
authors.affiliation: First Department of Surgery, Hokkaido University School of Medicine, Sapporo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Noto
authors.forename: M
authors.initials: M
authors.lastname: Matsushita
authors.forename: M
authors.initials: M
authors.lastname: Koike
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: H
authors.initials: H
authors.lastname: Matsue
authors.forename: J
authors.initials: J
authors.lastname: Kimura
authors.forename: S
authors.initials: S
authors.lastname: Todo
mesh_terms: D000410:Alanine Transaminase / Q000032:analysis; D000818:Animals; D001647:Bile Acids and Salts / Q000633:toxicity*; D002478:Cells, Cultured; D002756:Cholagogues and Choleretics / Q000633:toxicity*; D004247:DNA / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000032:analysis; D005999:Glycochenodeoxycholic Acid / Q000633:toxicity; D006000:Glycocholic Acid / Q000633:toxicity; D006501:Hepatic Encephalopathy / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013655:Taurochenodeoxycholic Acid / Q000633:toxicity; D013656:Taurocholic Acid / Q000633:toxicity; D014508:Urea / Q000032:analysis
chemical_list: D001647:Bile Acids and Salts; D002756:Cholagogues and Choleretics; D013655:Taurochenodeoxycholic Acid; D013656:Taurocholic Acid; D005999:Glycochenodeoxycholic Acid; D014508:Urea; D004247:DNA; D000410:Alanine Transaminase; D006000:Glycocholic Acid; D005947:Glucose