title: Estradiol-17 beta-glucuronide-induced cholestasis. Effects of ursodeoxycholate-3-O-glucuronide and 3,7-disulfate.
abstract: 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.
authors.affiliation: Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Sano
authors.forename: H
authors.initials: H
authors.lastname: Takikawa
authors.forename: M
authors.initials: M
authors.lastname: Yamanaka
mesh_terms: D000818:Animals; D001646:Bile / Q000378:metabolism*; D002756:Cholagogues and Choleretics / Q000008:administration & dosage*; D002779:Cholestasis / Q000139:chemically induced / Q000188:drug therapy*; D004958:Estradiol / Q000031:analogs & derivatives; D006933:Hyperbilirubinemia, Hereditary / Q000235:genetics / Q000378:metabolism; D007536:Isomerism; D008297:Male; D051381:Rats; D011922:Rats, Mutant Strains; D013655:Taurochenodeoxycholic Acid / Q000008:administration & dosage; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D002756:Cholagogues and Choleretics; C076255:ursodeoxycholic acid 3,7-disulfate; C076256:ursodeoxycholic acid-3-O-glucuronide; C025483:estradiol-17 beta-glucuronide; D004958:Estradiol; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D014580:Ursodeoxycholic Acid