The liver excretes large amounts of heme into bile when heme oxygenase is inhibited competitively by Sn-protoporphyrin

A. Kappas, C. S. Simionatto, G. S. Drummond, S. Sassa, K. E. Anderson

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


Tin(IV) protoporphyrin IX (Sn-protoporphyrin) potently inhibits heme degradation to bilirubin in vitro and in vivo, and it completely suppresses neonatal hyperbilirubinemia in experimental animals, including primates. It also reduces plasma bilirubin levels in certain naturally occurring or induced forms of jaundice in animals and man. We have examined in this study the fate of that fraction of heme whose degradation to bile pigment is inhibited in vivo by administration of this heme oxygenase (EC inhibitor. In bile-duct-cannulated rats, infused exogenous heme is rapidly converted to biliary bilirubin; a small amount of the infused heme is excreted into bile as well. Sn-protoporphyrin, administered with the exogenous heme, markedly increased (3- to 4-fold) the amount of heme excreted into bile and greatly diminished biliary output of bilirubin. The increase in biliary heme output exceeded the decrease in bilirubin excretion elicited by the inhibitor metalloporphyrin. In the same experimental model, Sn-protoporphyrin substantially decreased the conversion of heme, derived from heat-damaged erythrocytes, to biliary bilirubin. This decrease in biliary bilirubin output was accounted for entirely by a prompt and marked increase in biliary excretion of unmetabolized heme. The enhanced biliary excretion of unmetabolized heme following administration of Sn-protoporphyrin is a newly defined and biologically important response associated with use of this synthetic heme analogue. The features of the action of this compound in vivo - suppression of formation of the potentially neurotoxic metabolite, bilirubin; enhancement of disposal of the untransformed substrate (heme) of the enzyme that it inhibits; and its own elimination without metabolic alteration - define some of the characteristics of a therapeutically useful chemical.

Original languageEnglish (US)
Pages (from-to)896-900
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number3
StatePublished - 1985
Externally publishedYes

ASJC Scopus subject areas

  • General


Dive into the research topics of 'The liver excretes large amounts of heme into bile when heme oxygenase is inhibited competitively by Sn-protoporphyrin'. Together they form a unique fingerprint.

Cite this