Effect of chenodeoxycholic and ursodeoxycholic acids on isolated adult human hepatocytes

Chenodeoxycholic and ursodeoxycholic are effective cholelitholytic agents, but differ in their side effects. Chenodeoxycholic acid administration induces diarrhea and a transient rise of GOT, which are virtually nonexistent with ursodeoxycholic acid treatment. Lithocholic acid, a bacterial metabolite of chenodeoxycholic acid, has been implicated as a possible hepatotoxin. In the present investigation, the effect of chenodeoxycholic acid or ursodeoxycholic acid and their glycine and taurine conjugates on isolated human hypatocytes was directly assessed. Chenodeoxycholic acid had drastic effects on isolated human hepatocytes by reducing the number of microvilli and disrupting cell membranes. Pronounced release of GOT was observed. In contrast, ursodeoxycholic acid produced only slight morphological changes and enzyme release. Conjugation of each respective bile acids had a moderating effect.