INFLUENCE OF ORAL TREATMENT WITH URSODEOXYCHOLIC AND TAUROURSODEOXYCHOLIC ACIDS ON ESTROGEN-INDUCED CHOLESTASIS IN RATS - EFFECTS ON BILE FORMATION AND LIVER PLASMA-MEMBRANES

In this study, we examined whether ursodeoxycholic acid (UDC) and its taurine conjugate, tauroursodeoxycholic acid (TUDC), given per os, can prevent the cholestasis induced in rats by 17-alpha-ethynyl estradiol (EE) and whether this protection is mediated by choleretic activity o r altered plasma membrane composition. EE (5 mg/kg body weight/day for 5 days) markedly reduced bile flow and bile salt secretion without si gnificantly affecting plasma membrane composition and function. Treatm ent with UDC or TUDC (100, 150 or 200 (TUDC only) mumol/100 g body wei ght/day for 5 days) did not significantly modify bile flow, but the bi le salt secretion rate increased in a dose-dependent manner. UDC was t he main biliary bile acid secreted in groups given higher doses of UDC or TUDC. At these dose levels, bile acid treatment did not affect pla sma membrane fluidity as assessed by fluorescence anisotropy, the chol esterol/phospholipid molar ratio as well as Na+K+- and Mg++ATPase acti vities. The highest dose of UDC and TUDC prevented the reduction of bo th bile flow and bile salt secretion induced by EE, reestablishing the se parameters to the values of the corresponding control for the UDC g roup. In conclusion, UDC and TUDC, given per os, improve EE-induced ch olestasis, an effect that cannot be attributed to choleretic activity or altered plasma membrane composition.