title: 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.affiliation: Rockefeller University Hospital, New York, NY 10021.
authors.forename: R E
authors.initials: RE
authors.lastname: Böni
authors.forename: R A
authors.initials: RA
authors.lastname: Huch Böni
authors.forename: R A
authors.initials: RA
authors.lastname: Galbraith
authors.forename: G S
authors.initials: GS
authors.lastname: Drummond
authors.forename: A
authors.initials: A
authors.lastname: Kappas
mesh_terms: D000747:Anemia, Hypochromic / Q000139:chemically induced; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006418:Heme / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors*; D007408:Intestinal Absorption / Q000187:drug effects*; D007422:Intestines / Q000187:drug effects / Q000201:enzymology; D007501:Iron / Q000378:metabolism*; D008297:Male; D008665:Metalloporphyrins / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D008665:Metalloporphyrins; C055421:tin mesoporphyrin; D006418:Heme; D007501:Iron; D006419:Heme Oxygenase (Decyclizing)