Objectives: 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.
Methods: 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.
Results: 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.
Conclusions: 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.