TIN-MESOPORPHYRIN INHIBITS HEME OXYGENASE ACTIVITY AND HEME-IRON ABSORPTION IN THE INTESTINE

Long-term treatment with the heme oxygenase inhibitor tin-mesoporphyri n produces an iron deficiency anemia in rats analogous to that we repo rted in patients with the Crigler-Najjar type I syndrome receiving pro longed treatment with the inhibitor to ameliorate severe jaundice [Ped iatrics 1992;89: 175-182]. A dose- and time-dependent inhibition of in testinal heme oxygenase is produced by tin-mesoporphyrin which is inde pendent of iron status of the animal. Tin-mesoporphyrin inhibits the i ntestinal enzyme whether administered orally or parenterally. Enzyme i nhibition by either route results in diminished uptake of Fe-59 from r adiolabelled heme in the gut. Since tin-mesoporphyrin stimulates excre tion of unmetabolized heme into bile its ability to inhibit intestinal heme oxygenase and to decrease heme-iron absorption in the gut probab ly 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 experim ental and therapeutic studies in diseases of iron metabolism.