Effects of Cobalt Chloride, Nickel Chloride, and Nickel Subsulfide Upon Erythropoiesis in Rats

The erythropoietic effects of sustained intraperitoneal (i.p.) administration of CoCl2 and NiCl2 were compared with the effects of a single intrarenal (i.r.) injection of alpha Ni3S2 in female Fischer-344 rats. Infusion of NiCl2 by osmotic minipumps (0.85 mg Ni per day, i.p., for 24 days; total dose = 20 mg Ni per rat) did not alter the blood hematocrit or reticulocyte count during six weeks of observation. Under identical conditions, i.p. infusion of CoCl2 (0.85 mg Co per day, i.p., for 24 days; total dose = 20 mg Co per rat) caused significant erythrocytosis (hematocrit at six weeks = 62 +/- 4 percent, P less than 0.001 versus 50 +/- 3 percent in controls) and reticulocytosis (reticulocyte count at three weeks = 2.5 +/- 1.5 percent, P less than 0.005 versus 0.8 +/- 0.7 percent in controls). Administration of alpha Ni3S2 to rats as a single i.r. injection (7 mg Ni per rat) caused pronounced erythrocytosis (hematocrit at six weeks = 79 +/- 2 percent, P less than 0.001 versus controls) and reticulocytosis (reticulocyte count at three weeks = 2.8 +/- 1.2 percent, P less than 0.005 versus controls). This study demonstrates that i.p. infusion of Ni[II] is ineffective in stimulating erythropoiesis in rats, and that salient differences exist between the enhanced erythropoiesis that occurs in rats following i.p. infusion of Co[II] and that produced by i.r. injection of alpha Ni3S2.