Comparative Pharmacology of Zinc Mesoporphyrin and Tin Mesoporphyrin: Toxic Actions of Zinc Mesoporphyrin on Hematopoiesis and Progenitor Cell Mobilization

Abstract

The effects of two synthetic heme analogues, zinc mesoporphyrin (ZnMP) and tin mesoporphyrin (SnMP), on in vivo hematopoietic progenitor cell mobilization and in vitro hematopoiesis were examined in rabbit bone marrow. Rabbits received granulocyte colony-stimulating factor (rhG-CSF) for 7 days in order to mobilize increased numbers of erythroid (BFU-E) and myeloid (CFU-GM) progenitors in peripheral blood. Concurrent treatment of rhG-CSF-treated rabbits with ZnMP reduced mobilization of the numbers of BFU-E (76% inhibition, p < 0.0001) and CFU-GM (70% inhibition, p < 0.005) in peripheral blood. In contrast, SnMP administered at the same concentration had no significant suppressive effect on BFU-E and CFU-GM recruitment. Both metalloporphyrins inhibited bone marrow heme oxygenase activity equally in vivo, thus indicating that both compounds enter bone marrow cells. Direct in vitro addition of ZnMP to normal rabbit bone marrow cultures suppressed BFU-E and CFU-GM growth, whereas SnMP had no such effect. These results confirm, in an in vivo system, our earlier in vitro studies and demonstrate that, at the concentrations studied, ZnMP, in contrast to SnMP, displays toxicity for hematopoietic growth and progenitor cell production.