Epomediol (1,3,3-trimethyl-2-oxabicyclo(2.2.2.)octan-6,7-endo,endo-diol) (EPO) is a
terpenoid compound shown to reverse 17 alpha-ethinylestradiol (EE)-induced
cholestasis in rat. The effect is related to the restoration of normal liver plasma membrane fluidity values. To further characterize the effect of EPO, bile flow and biliary
lipid composition were measured in rats treated either with EE or EE associated with EPO. EE significantly reduced the bile flow; this reduction was prevented by concomitant treatment with EPO with an increase in the
bile salt secretion rate. EPO alone showed a choleretic effect. The biliary secretion rate of
cholesterol was also significantly reduced by EE while being comparable to controls in EE-EPO-treated animals.
Phospholipid (PL) biliary excretion was significantly (P less than 0.002) increased by EE either alone or combined with EPO. After EE treatment, the biliary PL composition showed a reduction in
phosphatidylcholine (PC) concentration with a parallel increase in lyso-
phosphatidylcholine (LPC) when compared to control animals (PC:LPC ratio 5.0 +/- 2.5 vs 26.8 +/- 9.9, mean +/- SD, P less than 0.005). EPO administration to EE-treated rats restored the biliary PC:LPC ratio to control values (27.6 +/- 10.6). EPO alone did not show any appreciable effect as compared to both control and EE-EPO treated animals. As increased concentrations of LPC have been reported to induce an alteration in the function of
membrane lipids and
membrane-associated proteins, such as regulatory
enzymes for
bile acid,
cholesterol and
phospholipid metabolism, these results suggest that the protective effect of EPO in EE-induced
cholestasis may be related to the reversal of the alterations in
membrane lipid composition and function induced by EE.