The Effect of Zinc Salts on Serum Bilirubin Levels in Hyperbilirubinemic Rats

Abstract

Intestinal metabolism of bilirubin is implicated in the pathogenesis of neonatal jaundice and Crigler-Najjar syndrome. In the present study the authors investigated the effect of oral administration of zinc salts on serum bilirubin levels in hyperbilirubinemic rats. Bilirubin-binding activities of zinc sulfate and water-insoluble zinc methacrylate were determined in vitro. Congenitally hyperbilirubinemic Gunn rats and artificially hyperbilirubinemic Wistar rats were used in in vivo studies. Animals were fed a normal diet for 1 week and then a treatment diet of either zinc sulfate or zinc methacrylate for additional 2 weeks. Serum and fecal bile pigments were determined at the end of each phase. Biliary bilirubin secretion rates were determined in hyperbilirubinemic Wistar rats fed zinc methacrylate. Substantial bilirubin-binding activities of zinc salts were demonstrated in in vitro experiments. Treatment with oral zinc salts significantly decreased serum bilirubin levels in Gunn rats (166 +/- 53 versus 123 +/- 38 and 206 +/- 34 versus 131 +/- 31 micromol/L, P < 0.05 for zinc methacrylate and zinc sulfate, respectively). A similar effect of zinc methacrylate was also observed in hyperbilirubinemic Wistar rats (102 +/- 10 versus 14 +/- 4 micromol/L, P < 0.0001). In accord, biliary bilirubin secretion decreased significantly in these animals (45 +/- 11 versus 28 +/- 4 nmol/h 100g body weight, P < 0.02). In contrast to zinc sulfate, treatment with zinc methacrylate did not lead to the elevation of serum zinc levels. Oral administration of zinc salts efficiently decreased serum bilirubin levels in hyperbilirubinemic rats, presumably as a result of inhibition of enterohepatic circulation of bilirubin. This approach might be useful in the treatment of severe unconjugated hyperbilirubinemias.