Effect of High Concentrations of Bile Acids on Cultured Hepatocytes

Authors: Noto, Hiromitsu1; Matsushita, Michiaki1; Koike, Masahiko1; Takahashi, Manabu1; Matsue, Hirokazu1; Kimura, Jun1; Todo, Satoru1

Source: Artificial Organs, Volume 22, Number 4, April 1998 , pp. 300-307(8)

Publisher: Blackwell Publishing

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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.

Keywords: Bile acids; Rat hepatocyte; C/CDC ratio; Hepatocellular injury

Document Type: Original article

DOI: 10.1046/j.1525-1594.1998.05071.x

Affiliations: 1: First Department of Surgery, Hokkaido University School of Medicine, Sapporo, Japan

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