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 or altered plasma membrane composition. EE (5 mg/kg body weight/day for 5 days) markedly reduced bile flow and bile salt secretion without significantly affecting plasma membrane composition and function. Treatment with UDC or TUDC (100, 150 or 200 (TUDC only) mumol/100 g body weight/day for 5 days) did not significantly modify bile flow, but the bile salt secretion rate increased in a dose-dependent manner. UDC was the main biliary bile acid secreted in groups given higher doses of UDC or TUDC. At these dose levels, bile acid treatment did not affect plasma membrane fluidity as assessed by fluorescence anisotropy, the cholesterol/phospholipid molar ratio as well as Na+K(+)- and Mg(++)-ATPase activities. The highest dose of UDC and TUDC prevented the reduction of both bile flow and bile salt secretion induced by EE, re-establishing these parameters to the values of the corresponding control for the UDC group. In conclusion, UDC and TUDC, given per os, improve EE-induced cholestasis, an effect that cannot be attributed to choleretic activity or altered plasma membrane composition.
Department of Pharmacology, Université de Montréal, Quebec, Canada.
G
G
Bouchard
I M
IM
Yousef
B
B
Tuchweber
D000284:Administration, Oral; D000818:Animals; D001646:Bile / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects; D002780:Cholestasis, Intrahepatic / Q000139:chemically induced / Q000517:prevention & control*; D004997:Ethinyl Estradiol; D005454:Fluorescence Polarization; D007536:Isomerism; D008099:Liver / Q000648:ultrastructure; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013655:Taurochenodeoxycholic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage / Q000627:therapeutic use*
D004997:Ethinyl Estradiol; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D014580:Ursodeoxycholic Acid