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
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.