Pharmacological and Biological Effects of Tin-Protoporphyrin on Neonatal Hyperbilirubinemic Gunn Rats

Publisher Website
Google Scholar
Abstract
Our study was undertaken to examine the pharmacological and biological effects of tin-protopor-phyrin, a competitive inhibitor of heme oxygenase, on 5-or 6-day-old homozygous (j/j) Gunn rats with hereditary unconjugated hyperbilirubinemia. When j/j neonates were injected subcutaneously with 20 μmol of tin-protopor-phyrin/kg of body weight, hepatic heme oxygenase activity decreased to 30% of the initial level 2 h after administration and remained low during the next 46 h. However, the reduction of serum bilirubin was more rapid and transient, reaching the minimum value (40% of the initial level) at 1 h and increasing thereafter at a rate almost comparable to that in nontreated j/j rats. The mortality rate of j/j rats was strikingly reduced by the administration of 1 to 100 μmol of tin-protoporphyrin/kg; the most effective dose was 5 μmol/kg (8% compared with 80% in non-treated j/j rats). However, the protective effect of tin-protoporphyrin on bilirubin cerebellopathy (cerebellar hypoplasia) was less marked than expected. Possible implications of our results are discussed.