Effects of ursodeoxycholate on maximal biliary secretion of bilirubin in the rat.
The effect of sodium ursodeoxycholate (0.5 and 1.0 mumol/min/100 g) on the maximal biliary secretion (Tm) of bilirubin and on the concentration of bilirubin in liver and plasma at the end of a bilirubin load was studied in Wistar rats. Administration of ursodeoxycholate at 0.5 mumol/min/100 g caused a 0.8-fold increase in bile flow and a significant increase in the bilirubin Tm (+24%). This was associated with a significant reduction of liver and plasma bilirubin concentrations (-16% and -17%, respectively). Bilirubin UDP-glucuronosyltransferase activity was not significantly enhanced. There was a significant increase in the biliary excretion of bilirubin conjugates (+30%) and in the diconjugates/monoconjugates ratio in bile (+31%). When ursodeoxycholate was given at 1.0 mumol/min/100 g, it produced a 1.7-fold increase in bile flow, but the bilirubin Tm was significantly reduced (-21%). Liver bilirubin concentrations were decreased (-20%) and there was a significant enhancement in total pigment concentration in plasma (+19%). Both the excretion of unconjugated bilirubin and that of bilirubin conjugates were significantly reduced (-60% and -18%, respectively). There was a significant decrease in the bilirubin-UDP glucuronosyltransferase activity and the diconjugates/monoconjugates ratio in bile (-27% and -27%, respectively). These results indicate that ursodeoxycholate is able to increase maximal bilirubin secretion only when administered at low doses and that infusion at higher rates can significantly interfere with different steps in the hepatobiliary transport of the pigment.
Galan
A I
AI
Department of Physiology and Pharmacology, University of Salamanca, Spain.
Jimenez
R
R
Muñoz
M E
ME
Gonzalez
J
J
D000818:Animals; D001646:Bile / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D001654:Bile Pigments / Q000378:metabolism; D001663:Bilirubin / Q000097:blood / Q000378:metabolism*; D003840:Deoxycholic Acid / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D005704:Gallbladder / Q000187:drug effects* / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D006602:Hexosyltransferases / Q000378:metabolism; D007262:Infusions, Intravenous; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage / Q000494:pharmacology*
D001647:Bile Acids and Salts; D001654:Bile Pigments; C019787:bilirubin glucuronoside glucuronosyltransferase; D003840:Deoxycholic Acid; D014580:Ursodeoxycholic Acid; D006602:Hexosyltransferases; D014453:Glucuronosyltransferase; D001663:Bilirubin