Estradiol-17 beta-glucuronide-induced cholestasis. Effects of ursodeoxycholate-3-O-glucuronide and 3,7-disulfate

J Hepatol. 1993 Feb;17(2):241-6. doi: 10.1016/s0168-8278(05)80045-5.


The effect of the co-infusion of ursodeoxycholate and its taurine conjugate, 3-O-glucuronide and 3,7-disulfate on estradiol-17 beta-glucuronide-induced cholestasis was examined. Estradiol-17 beta-glucuronide was intravenously administered to bile-drained rats at a rate of 0.075 mumol/min/100 g for 20 min. Co-infusion of ursodeoxycholate and its conjugates was simultaneously begun at a rate of 0.2 mumol/min/100 g and continued for 120 min. Ursodeoxycholate failed to improve and tauroursodeoxycholate only partially improved estradiol-17 beta-glucuronide-induced cholestasis between 20 and 40 min, although both bile acids increased bile flow after 80 min. Tauroursodeoxycholate increased biliary estradiol-17 beta-glucuronide excretion. Ursodeoxycholate-3-O-glucuronide completely inhibited cholestasis induced by estradiol-17 beta-glucuronide without changing biliary estradiol-17 beta-glucuronide excretion. Although ursodeoxycholate-3,7-disulfate had only a minor effect on cholestasis, it increased biliary excretion of estradiol-17 beta-glucuronide. In the Eizai hyperbilirubinuria rat (EHBR), a hyperbilirubinemic mutant Sprague-Dawley rat, the same dose of estradiol-17 beta-glucuronide failed to induce cholestasis with a marked delay in biliary excretion of estradiol-17 beta-glucuronide. In summary, ursodeoxycholate-3-O-glucuronide is more effective than tauroursodeoxycholate in inhibiting estradiol-17 beta-glucuronide-induced cholestasis and ursodoexycholate-3,7-disulfate had little effect. However, the unexpected effects of ursodeoxycholate-3-O-glucuronide and 3,7-disulfate on excretion of estradiol-17 beta-glucuronide suggest that the interaction of these anions at the canalicular membrane is complicated, with interaction occurring at more than two pathways of the biliary excretion of these anions.

MeSH terms

  • Animals
  • Bile / metabolism*
  • Cholagogues and Choleretics / administration & dosage*
  • Cholestasis / chemically induced
  • Cholestasis / drug therapy*
  • Estradiol / analogs & derivatives
  • Hyperbilirubinemia, Hereditary / genetics
  • Hyperbilirubinemia, Hereditary / metabolism
  • Isomerism
  • Male
  • Rats
  • Rats, Mutant Strains
  • Taurochenodeoxycholic Acid / administration & dosage
  • Ursodeoxycholic Acid / administration & dosage
  • Ursodeoxycholic Acid / analogs & derivatives*


  • Cholagogues and Choleretics
  • ursodeoxycholic acid 3,7-disulfate
  • ursodeoxycholic acid-3-O-glucuronide
  • estradiol-17 beta-glucuronide
  • Estradiol
  • Taurochenodeoxycholic Acid
  • ursodoxicoltaurine
  • Ursodeoxycholic Acid