Effective treatment of unconjugated hyperbilirubinemia with oral bile salts in Gunn rats.
OBJECTIVE
We tested the hypothesis that oral administration of bile salts, which are known to increase the biliary excretion of unconjugated bilirubin (UCB), decreases unconjugated hyperbilirubinemia in the Gunn rat model.


METHODS
Adult Gunn rats were fed a standard diet or the same diet supplemented with 0.5 weight % ursodeoxycholic acid (UDCA) or cholic acid (CA) for 1 or 6 weeks. UCB and urobilinoids, a family of intestinal UCB breakdown products, were determined in plasma, feces, or both. After 6 weeks of treatment, tracer 3H-UCB was administered intravenously to determine steady-state UCB kinetics over the next 60 hours.


RESULTS
One-week treatment with UDCA or CA decreased plasma UCB concentrations by 21% and 30%, respectively (each P < .01). During the first 4 days of treatment, both UDCA and CA increased the combined fecal excretion of UCB and urobilinoids (+52% and +32%, respectively; each P < .01). Prolongation of treatment to 6 weeks caused a persistent decrease in plasma UCB concentrations to approximately 40% below baseline (each bile salt P < .001). (3)H-UCB kinetic studies showed that UDCA and CA administration decreased UCB pool size (-33% and -32%, respectively; each P < .05) and increased UCB fractional turnover (+33% and +25%, respectively; each P < .05).


CONCLUSIONS
Dietary bile salt administration induces a large, persistent decrease in plasma UCB concentrations in Gunn rats. Both UDCA and CA enhance UCB turnover by increasing its fecal disposal. These results support the application of oral bile salt treatment in patients with unconjugated hyperbilirubinemia.
Cuperus
Frans J C
FJ
Pediatric Gastroenterology, Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Hafkamp
Anja M
AM
Havinga
Rick
R
Vitek
Libor
L
Zelenka
Jaroslav
J
Tiribelli
Claudio
C
Ostrow
J Donald
JD
Verkade
Henkjan J
HJ
D000284:Administration, Oral; D000818:Animals; D001647:Bile Acids and Salts / Q000008:administration & dosage / Q000627:therapeutic use*; D001663:Bilirubin / Q000378:metabolism; D019826:Cholic Acid / Q000008:administration & dosage / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005243:Feces; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006932:Hyperbilirubinemia / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051381:Rats; D014316:Tritium; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage / Q000627:therapeutic use
D001647:Bile Acids and Salts; D005765:Gastrointestinal Agents; D014316:Tritium; D014580:Ursodeoxycholic Acid; D019826:Cholic Acid; D001663:Bilirubin