Influence of dietary calcium phosphate on the disposition of bilirubin in rats with unconjugated hyperbilirubinemia.
The aim of this study was to test a possible form of therapy that could be used in the management of unconjugated hyperbilirubinemia. We hypothesized that unconjugated bilirubin (UCB) can permeate the intestinal wall and can thus be secreted with the feces. We have previously observed that UCB binds to amorphous calcium phosphate in vitro. Orally ingested amorphous calcium phosphate may act as a trapping agent for bilirubin in the intestine, thereby preventing back-diffusion across the intestinal wall. In this study, we tested whether feeding calcium phosphate leads to enhanced excretion of unconjugated bilirubin in Gunn rats. When a purified control diet was substituted by a high calcium phosphate diet, a decrease in bilirubin levels of 30% to 50% in male Gunn rats and of 23% in female rats was observed. The fecal output of bilirubin was more than doubled in Gunn rats in the first 3 days after the normal diet had been replaced by the high calcium-phosphate diet. The biological half-life of 3 H-labeled bilirubin in blood was 89.8 +/- 17.2 hours in rats fed the purified control diet and 50.9 +/- 1.4 hours in rats fed the high calcium phosphate diet (P = .004). After 30 weeks, plasma bilirubin levels were still significantly lower in Gunn rats fed a high calcium phosphate diet. No differences were found in plasma concentrations of calcium, magnesium, phosphate, urea, and creatinine in both Gunn rats and Wistar rats on control or high calcium phosphate diets. This therapy might be useful in the management of Crigler-Najjar patients, for example, as an adjunct to phototherapy.
Van Der Veere
C N
CN
Department of Gastrointestinal and Liver Diseases, Academic Medical Center, Amsterdam, The Netherlands.
Schoemaker
B
B
Bakker
C
C
Van Der Meer
R
R
Jansen
P L
PL
Elferink
R P
RP
D000818:Animals; D001646:Bile / Q000378:metabolism; D001663:Bilirubin / Q000097:blood / Q000378:metabolism*; D002130:Calcium Phosphates / Q000008:administration & dosage* / Q000494:pharmacology; D004032:Diet; D005243:Feces / Q000737:chemistry; D005260:Female; D006932:Hyperbilirubinemia / Q000378:metabolism*; D008297:Male; D051381:Rats; D011911:Rats, Gunn; D017208:Rats, Wistar; D013997:Time Factors
D002130:Calcium Phosphates; C485828:alpha-tricalcium phosphate; C519480:amorphous calcium phosphate; C485830:tetracalcium phosphate; C485838:calcium phosphate, monobasic, anhydrous; C020243:calcium phosphate; C485829:calcium phosphate, dibasic, anhydrous; D001663:Bilirubin