INTESTINAL EXCRETION OF UNCONJUGATED BILIRUBIN IN MAN AND RATS WITH INHERITED UNCONJUGATED HYPERBILIRUBINEMIA

Citation
P. Kotal et al., INTESTINAL EXCRETION OF UNCONJUGATED BILIRUBIN IN MAN AND RATS WITH INHERITED UNCONJUGATED HYPERBILIRUBINEMIA, Pediatric research, 42(2), 1997, pp. 195-200
Citations number
38
Categorie Soggetti
Pediatrics
Journal title
ISSN journal
00313998
Volume
42
Issue
2
Year of publication
1997
Pages
195 - 200
Database
ISI
SICI code
0031-3998(1997)42:2<195:IEOUBI>2.0.ZU;2-U
Abstract
Patients with Crigler-Najjar syndrome and Gunn rats cannot form biliru bin glucuronides owing to a lack of bilirubin UDP-glucuronosyltransfer ase activity. Because increased serum and tissue bilirubin levels rema in constant, an alternative excretory route has to substitute for this deficiency. Gunn rats excrete in bile only 2-13% of the bilirubins el iminated in Wistar rats. In contrast, the biliary excretion rate of ur obilinogen in Gunn and Wistar rats is comparable. The sum of bilirubin s and urobilinogen excreted in the bile of Gum rats amounts to 10-30% of pigments excreted in Wistar rats. Despite this low biliary excretio n, the intestinal content and fecal excretion of bile pigments in Gunn and Wistar rats were similar. These data support an extrabiliary entr ance of unconjugated bilirubin into the intestine. Additional proof fo r this was found in that the intestinal lumen of Gunn rats still conta ins a high amount of bilirubins and urobilinogen after 3 d of external biliary drainage. A similar procedure in Wistar rats resulted in the complete disappearance of bile pigments from the intestine. The direct transmural transport of bilirubin from blood to all parts of the inte stinal lumen was demonstrated by injecting C-14-bilirubin i.v. into Gu nn rats with isolated parts of small and large intestine. In Crigler-N ajjar and Gilbert's syndrome patients, the biliary excretion of bile p igments has previously been shown to be strongly reduced. Their stools , however, contained approximately the same amount of bile pigments as in normal subjects. Although only traces of unconjugated bilirubin we re detected in the stool of normal persons (4 +/- 3% of total bile pig ments), higher amounts were found in patients with Crigler-Najjar dise ase (20 +/- 12&). These results suggest a direct intestinal permeation of unconjugated bilirubin in severe unconjugated hyperbilirubinemia b oth in man and rats.