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.

Dietary hemoglobin rescues young piglets from severe iron deficiency anemia: Duodenal expression profile of genes involved in heme iron absorption

“…In most mammalian species, with the exception of mice [51], HO1-mediated heme catabolism in absorptive enterocytes seems to be the limiting step in dietary heme iron assimilation. Consequently, HO1 inhibitors have been shown to inhibit the absorption of heme iron [52]. We observed a profound induction of the Hmox1 gene in the enterocytes of piglets fed a hemoglobin-enriched diet.…”

Metalloporphyrins – An Update

“…Iron deficiency anemia has been reported following long-term treatment with SnMP in rats (Boni et al, 1993) and patients with Crigler–Najjar Syndrome Type I (110 doses of SnMP 0.5 or 1.0 μmol/kg BW during a 400-day study; Boni et al, 1993; Kappas et al, 1993). Because SnMP inhibits intestinal HO (Vreman et al, 1989) and decreases intestinal heme–iron absorption (Boni et al, 1993), this may account for the iron deficiency-like anemia that results after long-term SnMP exposure.…”

“…Because SnMP inhibits intestinal HO (Vreman et al, 1989) and decreases intestinal heme–iron absorption (Boni et al, 1993), this may account for the iron deficiency-like anemia that results after long-term SnMP exposure. Kappas et al (1993) reported that the deficiency was easily reversed by supplementation with iron.…”

Cardiac Protection by Preconditioning Is Generated via an Iron-Signal Created by Proteasomal Degradation of Iron Proteins

“…We used Sn-Mesoporphyrin (SnMP), a potent competitive inhibitor of HO [35], to examine this possibility. After stabilization, a non-toxic dose of 20 µmol/L SnMP was added to the perfusion medium (KH-buffer), before the I/R procedure, with or without prior IPC (Figure1, groups 1–3, and Table 1).…”