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: N Sano, H Takikawa, M Yamanaka
• Journal: Journal of hepatology (J Hepatol) Vol. 17 Issue 2 Pg. 241-6 (Feb 1993) ISSN: 0168-8278 [Print] Netherlands
• PMID: 8445238 (Publication Type: Journal Article)

Chemical References

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

Topics

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