Antisickling agents: effects of carbamyl phosphate or cyanate on survival, erythrocytes, and leucocytes in the mouse

Equal mole doses of the anions of disodium carbamyl phosphate (carbamyl P) or sodium cyanate, antisickling agents, have been compared in C57B1 mice. Using 15 mice per group, two groups were given the equivalent ip dose of carbamyl P or cyanate anion (7 mmoles/kg/day) in a divided dose, in the morning and six hours later, for 17--18 days. The control group received sodium chloride (13.8 mmoles of Na+ or Cl-/kg/day). Surviving mice per group were sodium chloride, 15/15; disodium carbamyl P, 14/15; and sodium cyanate, 0/15, all mice died by day 2. Surviving mice appeared normal throughout the study, and no abnormalities were seen at necropsy. The hematologic measurements were the same for sodium chloride or disodium carbamyl P, including hemoglobin, packed cell volume, erythrocyte counts, leucocyte counts, and differential counts. The mean hemoglobin carbamylation was 1.24 (+/- 0.06 SE) moles of valine hydantoin/mole of hemoglobin tetramer in mice receiving disodium carbamyl P for 18 days, sufficient for antisickling activity. The enzymatic degradation of carbamyl P to NH3, CO2, and Pi was measured in serial blood samples in additional C57B1 and DBA/2J mice following ip injections of carbamyl P or cyanate. Both NH3 and Pi increased immediately after giving carbamyl P, but no increase occurred after cyanate administration. Thus enzymatic degradation of carbamyl P occurs in vivo and appears to be an important detoxification mechanism. When equivalent mole doses of anion are administered, disodium carbamyl P is less toxic than sodium cyanate in mice.