Abstract
In order to estimate the hepatotoxicity of bile acids such as chenodeoxycholate (CDCA), deoxycholate (DCA), ursodeoxycholate (UDCA) and cholate (CA), we studied the effect of these bile acids on the release of various cytosolic and mitochondrial enzymes and protein into the incubation medium and on cell mortality in liver cells isolated from adult male rats.
Liver cells showed little change either in the release of cytosolic enzymes such as lactate dehydrogenase (LDH), glutamic-Pyruvic transaminase (GPT) and malate dehydrogenase (MDHs) and mitochondrial enzymes such as malate dehydrogenase (MDHm) and glutamic-oxaloacetic transaminase (GOTm), and protein immediately after addition of bile acids to the medium. When liver cells were incubated with each bile acid at 37°C for 60 min, both hepatic cell mortality and the ratio of enzymes and protein from the cells increased concomitantly with an increase in the concentration of bile acids added. There was a clear difference in the abilty to cause these changes among the four bile acids: COCA>DCA> UDCA>CA. Of hepatic cytosolic and mitochondrial enzymes determined in the medium under these conditions, MDHs showed the highest activity, while LDH and GPT were higher in the ratio of enzyme release than MDHs, MDHm and GOTm. In addition, the ratios of LDH and GPT activities in the medium total activities in the cells increased almost in accordance with cell mortality. It was also found histologically that the plasma membrane and mitochondria of liver cells were damaged by treatment with bile acids at 37°C for 60 min.
