Comparative pharmacology of zinc mesoporphyrin and tin mesoporphyrin: Toxic actions of zinc mesoporphyrin on hematopoiesis and progenitor cell mobilization

The effects of two synthetic heme analogues, zinc mesoporphyrin (ZnMP) and tin mesoporphyrin (SnMP), on in vivo hematopoietic progenitor cell mobiliza tion and in vitro hematopoiesis were examined in rabbit bone marrow. Rabbit s received granulocyte colony-stimulating factor (rhG-CSF) for 7 days in or der to mobilize increased numbers of erythroid (BFU-E) and myeloid (CFU-GM) progenitors in peripheral blood. Concurrent treatment of rhG-CSF-treated r abbits with ZnMP reduced mobilization of the numbers of BFU-E (76% inhibiti on, p < 0.0001) and CFU-GM (70% inhibition, p < 0.005) in peripheral blood. In contrast, SnMP administered at the same concentration had no significan t suppressive effect on BFU-E and CFU-GM recruitment, Both metalloporphyrin s inhibited bone marrow heme oxygenase activity equally in vivo, thus indic ating 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 vi vo system, our earlier in vitro studies and demonstrate that, at the concen trations studied, ZnMP, in contrast to SnMP, displays toxicity for hematopo ietic growth and progenitor cell production.