Tin-protoporphyrin suppression of hyperbilirubinemia in mutant mice with severe hemolytic anemia.
Tin-protoporphyrin is a potent competitive inhibitor of heme oxygenase both in vivo in animals and in vitro in isolated enzyme preparations, and when administered to neonatal rats, prevents the development of postnatal hyperbilirubinemia. In this study we examined the effect of the metalloporphyrin on the activity of heme oxygenase in liver, kidney, and spleen, and on the level of bilirubin in plasma in three types of anemic mutant mice with severe hemolytic diseases. We report that the administration of tin-protoporphyrin to anemic mutants homozygous for severe hemolytic disease results in substantial inhibition of heme oxidation in liver, spleen, and kidney and in significant reduction of plasma bilirubin levels. Tin-protoporphyrin thus has the capacity to significantly inhibit in vivo heme degradation and to concurrently diminish plasma bilirubin levels in severe chronic hemolytic disorders.
D000743:Anemia, Hemolytic / Q000150:complications*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D006932:Hyperbilirubinemia / Q000150:complications / Q000188:drug therapy*; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008665:Metalloporphyrins; D051379:Mice; D008817:Mice, Mutant Strains; D011166:Porphyrins / Q000627:therapeutic use*; D011524:Protoporphyrins / Q000008:administration & dosage / Q000627:therapeutic use*; D013154:Spleen / Q000201:enzymology
D008665:Metalloporphyrins; D011166:Porphyrins; D011524:Protoporphyrins; C032628:tin protoporphyrin IX; D006419:Heme Oxygenase (Decyclizing)