抄録
Rat livers were perfused for 4 hours, and bile-duct ligation and the addition of bile acids such as chenodeoxycholate (CDCA), ursodeoxycholate (UDCA), deoxy-cholate (DCA) and cholate (CA) into the perfusion medium were conducted 30 min after the start of perfusion. Activities of the following enzymes released into the perfusate were determined at intervals of 30min during the per fusion: lactate dehydrogenase (LDH5), malate dehydrogenase (MDHs), glutamic-pyruvic transaminase (GPT) and α-hydroxybutyrate dehydrogenase (α-HBD) which are distributed in hepatic soluble fraction, and malate dehydrogenase (MDHm) and glutamic-oxaloacetic transaminase (GOTm) which are distributed in the mitochondrial fraction. The perfusion of livers with bile-duct ligation caused a much higher time-dependent increase of all enzyme activities in the perfusate than that of control livers, in which LDH5, MDHs and MDHm showed a marked increase in activitis as compared with GPT, α-HBD and GOTm. The perfusion of livers with the medium containing 0.01% CDCA, 0.01% DCA, 0.05% UDCA or 0.05% CA caused the time-dependent increase in activities of all six enzymes in the perfusate just as the case of bile-duct ligation. CDCA and DCA showed a stronger effect on release of enzymes from liver than UDCA and CA.
The present results suggest that the injurious effect of bile-duct ligation on liver cells may be partly due to the cytotoxic effect on bile acids accumulated in the tissue, and that CDCA and DCA have a more toxic effect on liver cells than UDCA and CA, in which these damages by bile acids occur not only in plasma membranes but also in mitochondria. In addition it was indicated that both LDH5 and MDHs, and MDHm are marker enzymes sensitive to the bile acid-induced damage of liver plasma membranes and mitochondria, respectively.
