Effect of high concentrations of bile acids on cultured hepatocytes.
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.
Noto
H
H
First Department of Surgery, Hokkaido University School of Medicine, Sapporo, Japan.
Matsushita
M
M
Koike
M
M
Takahashi
M
M
Matsue
H
H
Kimura
J
J
Todo
S
S
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
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