title: Effect of some sulfonate analogues of ursodeoxycholic acid on biliary lipid secretion in the rat.
abstract: The effect of the sulfonate analogues of ursodeoxycholic acid, namely sodium 3 alpha,7 beta-dihydroxy-24-nor-5 beta-cholane-23-sulfonate (norUDC-SO3Na) and sodium 3 alpha, 7 beta-dihydroxy-5 beta-cholane-24-sulfonate (UDC-SO3Na), on biliary lipid secretion was studied in bile fistula rats. During intravenous infusion of the two sulfonate analogues, bile flow and biliary lipid secretion were stimulated in a dose-dependent manner. This suggests that the analogues exert an effect on biliary lipid secretion comparable to that of the naturally occurring bile acid, ursodeoxycholyltaurine (UDC-tau). The effects of norUDC-SO3Na and UDC-SO3Na on bile flow were similar but slightly smaller than that of UDC-tau. The output of bile salts was similar with both sulfonates but greater than that with UDC-tau. The infusion of norUDC-SO3Na or UDC-SO3Na induced cholesterol secretion and phospholipid secretion more significantly than UDC-tau infusion. The increase in phospholipid secretion was particularly pronounced during high-dose administration of norUDC-SO3Na. Although norUDC-SO3Na stimulated cholesterol secretion more intensely than the other two bile salts, it also facilitated phospholipid output, perhaps as a compensatory mechanism, and the biliary cholesterol/phospholipid ratio was decreased to a greater extent by the sulfonates than by UDC-tau. Consequently, the administration of norUDC-SO3Na or UDC-SO3Na produces a more "stable" bile than UDC-tau, suggesting that these sulfonates possess potential cholelitholytic activity.
authors.affiliation: Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Mikami
authors.forename: K
authors.initials: K
authors.lastname: Kihira
authors.forename: S
authors.initials: S
authors.lastname: Ikawa
authors.forename: M
authors.initials: M
authors.lastname: Yoshii
authors.forename: E H
authors.initials: EH
authors.lastname: Mosbach
authors.forename: T
authors.initials: T
authors.lastname: Hoshita
mesh_terms: D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism*; D002635:Chenodeoxycholic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002784:Cholesterol / Q000378:metabolism*; D005402:Fistula; D005704:Gallbladder / Q000601:surgery; D007700:Kinetics; D008297:Male; D010743:Phospholipids / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
chemical_list: D001647:Bile Acids and Salts; D010743:Phospholipids; D002635:Chenodeoxycholic Acid; C065714:3,7-dihydroxycholane-24-sulfonate; C078692:3,7-dihydroxy-24-norcholane-23-sulfonate; D014580:Ursodeoxycholic Acid; D002784:Cholesterol