The effect of tin-protoporphyrin on bilirubin conjugation and production in cholestatic rats.

Tin-protoporphyrin (SnP) is actively being investigated for treatment of exaggerated neonatal hyperbilirubinemia. Because both bilirubin conjugation and excretion are immature in the human newborn, we investigated the effect of SnP on bilirubin-conjugating mechanisms and the efficacy of SnP in suppressing serum bilirubin levels in adult rats made cholestatic by surgical bile duct ligation. Male Sprague-Dawley rats received SnP (100 mumol/kg body weight) subcutaneously either 24 h before or 24 or 48 h after bile duct ligation. Serum and urine specimens were collected 72 h after bile duct ligation and analyzed for bilirubin and its conjugates. As compared to a control group that received bile duct ligation and a sodium phosphate buffer injection, all SnP-treated animals had a significant lowering of total serum bilirubin levels. No differences in the distribution of serum bilirubin mono- and diconjugates in serum or urine samples were observed. However, the concentrations of covalently linked bilirubinprotein conjugates were significantly higher in the control cholestatic rats when compared to the SnP-treated animals. SnP effectively lowers serum bilirubin levels in rats with an impaired biliary excretory pathway for SnP. There was no adverse effect on bilirubin conjugation and no observable toxicity.