Zinc salts precipitate unconjugated bilirubin in vitro and inhibit enterohepatic cycling of bilirubin in hamsters.
BACKGROUND
We have evidence for enterohepatic cycling of bilirubin experimentally and in vivo in humans. This study was designed to investigate whether Zn salts might inhibit such cycling of bilirubin.


METHODS
Micellar bile salt solutions with unconjugated bilirubin were prepared, appropriate concentrations of Zn salts were added, and unconjugated bilirubin precipitation was measured. Hamsters and Wistar rats were fed a chow diet or a chow diet enriched with 1% ZnSO4, and bilirubin secretion rates were monitored.


RESULTS
Unconjugated bilirubin was precipitated maximally (90%) after a 10-min incubation with 5 mM Zn salts in the pH range of 6.8-9.0. In control hamsters, total bilirubin secretion rates into bile were 36.0 +/- 2.8 nmol h(-1) 100g(-1) body weight, whereas they were 25.0 +/- 3.3 nmol h-1 100(-1) g in the ZnSO4 group (P < 0.05).


CONCLUSIONS
Zn salts that flocculate at physiological pH adsorb unconjugated bilirubin almost completely from unsaturated micellar BS solutions. In addition, Zn salts administered orally suppress biliary bilirubin secretion rates in hamsters. These findings suggest that the administration of Zn salts may inhibit the enterohepatic cycling of unconjugated bilirubin in humans who are predisposed to pigment gallstone formation due to diet, disease or drugs.
Méndez-Sánchez
N
N
Medica Sur Clinic Foundation and National Autonomous University of Mexico (UNAM), Mexico City, Mexico. nmendez@medicasur.org.mx
Roldán-Valadez
E
E
Flores
M A
MA
Cárdenas-Vázquez
R
R
Uribe
M
M
D000818:Animals; D001647:Bile Acids and Salts / Q000737:chemistry / Q000494:pharmacology; D001658:Biliary Fistula / Q000378:metabolism; D001663:Bilirubin / Q000737:chemistry / Q000378:metabolism*; D002254:Carbonates / Q000737:chemistry / Q000494:pharmacology; D011232:Chemical Precipitation; D002769:Cholelithiasis / Q000378:metabolism; D006224:Cricetinae; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D051381:Rats; D017208:Rats, Wistar; D019345:Zinc Acetate / Q000737:chemistry / Q000494:pharmacology; D017967:Zinc Compounds / Q000737:chemistry / Q000494:pharmacology; D019287:Zinc Sulfate / Q000737:chemistry / Q000493:pharmacokinetics*
D001647:Bile Acids and Salts; D002254:Carbonates; D017967:Zinc Compounds; D019287:Zinc Sulfate; C036650:zinc carbonate; D019345:Zinc Acetate; D001663:Bilirubin