Enhanced biliary excretion of lithocholate-3-sulfate by ursodeoxycholate-3,7-disulfate infusion in Eisai hyperbilirubinemic rat (EHBR).

Biliary excretion of lithocholate-3-sulfate and ursodeoxycholate 3,7-disulfate is markedly impaired in EHBR. In the present study, the effects of ursodeoxycholate 3,7-disulfate infusion on lithocholate-3-sulfate excretion were studied in EHBR and Sprague-Dawley rats. Although in control rats, ursodeoxycholate 3,7-disulfate infusion had no effect on biliary lithocholate-3-sulfate excretion, in EHBR it enhanced biliary lithocholate-3-sulfate excretion. Although ursodeoxycholate 3,7-disulfate dose-dependently inhibited lithocholate-3-sulfate binding by rat serum albumin and rat liver cytosol, it did not affect the serum clearance of lithocholate-3-sulfate in EHBR in vivo. These findings indicate that in EHBR, in which the major ATP-dependent organic anion transporter is impaired, the excretory pathway for ursodeoxycholate 3,7-disulfate may interact to that for lithocholate-3-sulfate.