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

Abstract

Epomediol is a terpenoid compound that has been reported to reverse 17alpha-ethinylestradiol-induced cholestasis and to have a choleretic effect related to the biliary secretion of epomediol glucuronide. The aim of this study was to investigate the contribution of changes in bile acid metabolism to epomediol-induced effects on bile formation. Twenty-four-hour bile collections were performed in animals that had received intraperitoneal epomediol for five days at 100 mg/kg daily. Epomediol-treated rats had a 24% larger bile acid pool and 28% greater bile acid synthesis than controls when measured by the "washout" technique. There was no change in the fractional turnover rate and the cycling frequency of the pool. Both basal bile flow and bile acid secretion were significantly increased (+42% and +74%, respectively). Linear regression analysis between bile flow and bile acid secretion revealed that both bile acid-dependent fraction and bile acid-independent fraction were significantly increased (+40 and +27, respectively), with no change in the choleretic capacity of bile acids. Cholesterol secretion was increased by 42%, but there were no significant differences in phospholipid secretion. Cholesterol 7alpha-hydroxylase and HMG-CoA reductase activities were significantly higher in epomediol-treated rats (+39% and +97%, respectively). The activities of NADPH-cytochrome c reductase and aniline hydroxylase were also significantly elevated (+26% and +64%, respectively). It is concluded that epomediol treatment expands the bile acid pool through an enhanced bile acid synthesis. Choleresis induced by the drug is partly related to the increase in bile acid secretion.