Differential effect of ursodeoxycholate and its taurine conjugate on biliary transport maximum of bilirubin in the rat.
The effects of ursodeoxycholate and its taurine conjugate on biliary Tm of bilirubin were evaluated in rats. Ursodeoxycholate was administered at four different doses (4, 8, 12 or 16 mumol per 100 g body wt i.v., followed by an i.v. infusion of 0.3, 0.6, 0.9 or 1.2 mumol/min per 100 g body wt, respectively), whereas tauroursodeoxycholate was administered only at the maximal dose. A dose-dependent diminution of bilirubin Tm was observed during ursodeoxycholate administration, which ranged from no effect at the lowest dose to a virtual excretory blockage at the highest dose. This was associated with an increase in bilirubin concentrations in both plasma and liver as well as in the fractional amount of conjugated pigment in both sites, suggesting an impairment of bilirubin transfer at the canalicular level. Incomplete taurine conjugation of ursodeoxycholate well correlated with these effects. Unlike ursodeoxycholate, tauroursodeoxycholate had no inhibitory effect on bilirubin Tm, although a slight inhibition of bilirubin uptake and bilirubin conjugation became apparent. Taken together, these results suggest that ursodeoxycholate interferes with the hepatobiliary transport of bilirubin by impairing its transfer at the canalicular level and that incomplete taurine conjugation appears to be a key factor determining this effect.
Sánchez Pozzi
E J
EJ
Instituto de Fisiología Experimental, Facultad de Ciencias Bioquímicas y Farmacéuticas, CONICET-U.N.R., Rosario, Argentina.
Mottino
A D
AD
Sisti
A
A
Roma
M G
MG
D000818:Animals; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D001663:Bilirubin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
D001647:Bile Acids and Salts; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D014580:Ursodeoxycholic Acid; D001663:Bilirubin