Prolonged clinical use of a heme oxygenase inhibitor: hematological evidence for an inducible but reversible iron-deficiency state.
The heme oxygenase inhibitor tin (Sn4+)-mesoporphyrin, administered to two 17-year-old Crigler-Najjar type I patients during a 400-day study to lower plasma bilirubin levels, also produced changes, beginning approximately 50 days after initiation of treatment, in hematological and iron metabolism indices consistent with the development of iron deficiency anemia. These indices were responsive to iron supplementation and reverted to normal after termination of inhibitor treatment. Tin-mesoporphyrin enhances biliary heme excretion and inhibits intestinal heme oxygenase when administered orally or parenterally; the changes in blood indices could thus reflect, in part, blockade of heme catabolism and therefore of uptake of heme-derived iron, by intestinal epithelium. This action of the inhibitor suggests that such agents may facilitate studies involving aberrant metabolism of heme-derived iron in humans and that they merit further investigation with respect to their potential value in enhancing iron disposal in certain disorders such as those related, for example, to transfusion-induced iron overload states.
Kappas
A
A
Rockefeller University Hospital, New York, NY 10021.
Drummond
G S
GS
Galbraith
R A
RA
D000293:Adolescent; D000747:Anemia, Hypochromic / Q000139:chemically induced* / Q000188:drug therapy; D003414:Crigler-Najjar Syndrome / Q000097:blood / Q000188:drug therapy*; D006403:Hematologic Tests; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors*; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007501:Iron / Q000097:blood / Q000627:therapeutic use; D008297:Male; D008665:Metalloporphyrins / Q000009:adverse effects* / Q000627:therapeutic use
D006454:Hemoglobins; D008665:Metalloporphyrins; C055421:tin mesoporphyrin; D007501:Iron; D006419:Heme Oxygenase (Decyclizing)