Tin-mesoporphyrin inhibits heme oxygenase activity and heme-iron absorption in the intestine.

Abstract

Long-term treatment with the heme oxygenase inhibitor tin-mesoporphyrin produces an iron deficiency anemia in rats analogous to that we reported in patients with the Crigler-Najjar type I syndrome receiving prolonged treatment with the inhibitor to ameliorate severe jaundice [Pediatrics 1992; 89: 175-182]. A dose- and time-dependent inhibition of intestinal heme oxygenase is produced by tin-mesoporphyrin which is independent of iron status of the animal. Tin-mesoporphyrin inhibits the intestinal enzyme whether administered orally or parenterally. Enzyme inhibition by either route results in diminished uptake of 59Fe from radiolabelled heme in the gut. Since tin-mesoporphyrin stimulates excretion of unmetabolized heme into bile its ability to inhibit intestinal heme oxygenase and to decrease heme-iron absorption in the gut probably accounts in part for the iron deficiency produced by the agent. The availability of an orally active agent which inhibits heme oxygenase and heme-iron absorption in the intestine may prove useful for experimental and therapeutic studies in diseases of iron metabolism.

• Authors: R E Böni, R A Huch Böni, R A Galbraith, G S Drummond, A Kappas
• Journal: Pharmacology (Pharmacology) Vol. 47 Issue 5 Pg. 318-29 (Nov 1993) ISSN: 0031-7012 [Print] Switzerland
• PMID: 8265722 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Metalloporphyrins
• tin mesoporphyrin
• Heme
• Iron
• Heme Oxygenase (Decyclizing)

Topics

• Anemia, Hypochromic (chemically induced)
• Animals
• Dose-Response Relationship, Drug
• Heme (metabolism)
• Heme Oxygenase (Decyclizing) (antagonists & inhibitors)
• Intestinal Absorption (drug effects)
• Intestines (drug effects, enzymology)
• Iron (metabolism)
• Male
• Metalloporphyrins (toxicity)
• Rats
• Rats, Sprague-Dawley
• Time Factors