Tissue distribution and disposition of tin-protoporphyrin, a potent competitive inhibitor of heme oxygenase

Karl Anderson, C. S. Simionatto, G. S. Drummond, A. Kappas

Research output: Contribution to journalArticle

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Abstract

Tin(Sn)-protoporphyrin is a potent competitive inhibitor of heme oxygenase and can also suppress naturally occurring or experimentally induced hyperbilirubinemia in animals. In this study we examined the plasma clearance of Sn-protoporphyrin, its persistence in tissues and the time course of heme oxygenase inhibition up to 7 days after administration of doses up to 50 μmol/kg b.w. to adult male rats. After s.c. doses the metalloporphyrin was rapidly and almost completely absorbed. Initial plasma clearance was log-linear with a T 1/2 of approximately 3 h after either i.v. or s.c. administration. Levels of Sn-protoporphyrin in most tissues rose during the first 2 h and persisted for up to 7 days. Concentrations were highest in kidney and liver, were considerably lower in spleen, lung, intestine, adrenal and testes, and as Sn-protoporphyrin concentrations in plasma declined, concentrations in these tissues eventually exceeded simultaneous plasma concentrations. This suggests a varying degree of uptake and binding of the metalloporphyrin in these tissues. There was little or no uptake of Sn-protoporphyrin in heart, brain and red cells. Markedly decreased heme oxygenase activity in liver, kidney and spleen peristed as did Sn-protoporphyrin up to 7 days. The total mount of Sn-protoporphyrin present in tissues and excreta was a fairly constant fraction of the dose (~50%) at time intervals up to 7 days after injection. These results indicate that single doses of Sn-protoporpyrin are rapidly cleared from plasma and persist in tissues and potently inhibit heme oxygenase activity for prolonged periods.

Original languageEnglish (US)
Pages (from-to)327-333
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume228
Issue number2
StatePublished - 1984
Externally publishedYes

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Heme Oxygenase (Decyclizing)
Tissue Distribution
Metalloporphyrins
Spleen
Kidney
Hyperbilirubinemia
tin protoporphyrin IX
Liver
Intestines
Testis
Lung
Injections
Brain

ASJC Scopus subject areas

  • Pharmacology

Cite this

Tissue distribution and disposition of tin-protoporphyrin, a potent competitive inhibitor of heme oxygenase. / Anderson, Karl; Simionatto, C. S.; Drummond, G. S.; Kappas, A.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 228, No. 2, 1984, p. 327-333.

Research output: Contribution to journalArticle

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