Enhancement of bile acid pool size, synthesis and secretion by epomediol in the rat

Epomediol is a terpenoid compound that has been reported to reverse 17 alph a-ethinylestradiol-induced cholestasis and to have a choleretic effect rela ted to the biliary secretion of epomediol glucuronide. The aim of this stud y was to investigate the contribution of changes in bile acid metabolism to epomediol-induced effects on bile formation. Twenty-four-hour bile collect ions were performed in animals that had received intraperitoneal epomediol for five days at 100 mg/kg daily. Epomediol-treated rats had a 24% larger b ile acid pool and 28% greater bile acid synthesis than controls when measur ed by the "washout" technique, There was no change ill the fractional turno ver rate and the cycling frequency of the pool. Both basal bile flow and bi le acid secretion were significantly increased (+42% and +74%, respectively ). Linear regression analysis between bile flow and bile acid secretion rev ealed that both bile acid-dependent fraction and bile acid-independent frac tion were significantly increased (+40 and +27, respectively), with no chan ge in the choleretic capacity of bile acids. Cholesterol secretion was incr eased by 42%, but there were no significant differences in phospholipid sec retion. Cholesterol 7 alpha-hydroxylase and HMG-CoA reductase activities we re significantly higher in epomediol-treated rats (+ 39% and +97%, respecti vely). The activities of NADPH-cytochrome c reductase and aniline hydroxyla se were also significantly elevated (+26% and +64%, respectively). It is co ncluded that epomediol treatment expands the bile acid pool through an enha nced bile acid synthesis. Choleresis induced by the drug is partly related to the increase in bile acid secretion.