Relationship between leukopenia and bone marrow myeloperoxidase in the rat treated with propylthiouracil.

The relationship between the toxic effect of propylthiouracil (PTU) and myeloperoxidase activity of rat bone marrow was examined. The administration of PTU for 1 or 2 weeks caused a decrease in leukocyte count with the concomitant inhibition of the activity of myeloperoxidase in the bone marrow. The decreases in both leukocyte counts and myeloperoxidase activity were restored to control levels at 2 weeks after the discontinuation of the administration. PTU treatment did not affect the affinity of H2O2 for the enzyme; however, an increase in the Km value for guaiacol was seen. PTU, incubated with bone marrow peroxidase in vitro increased the Km value of the enzyme for guaiacol, but had no effect on the Km value for H2O2. The results suggest that the mechanism of inhibition of myeloperoxidase activity by PTU given in vivo or incubated with the enzyme in vitro may be the same. The activity of bone marrow glutathione peroxidase was not influenced by PTU treatment.