INCREASED SERUM ERYTHROPOIETIN ACTIVITY IN RATS FOLLOWING INTRA-RENAL INJECTION OF NICKEL SUBSULFIDE

Abstract

To investigate the pathophysiologic mechanisms of Ni-induced erythrocytosis, serum erythropoietin activities were measured in pooled serum from rats at 2 wk after intrarenal injection of .alpha.Ni3S2 [5 mg/rat] and pooled serum from control rats at 2 wk after intrarenal injection of sterile NaCl vehicle [0.4 ml/rat]. A sensitive erythropoietin bioassay was employed, which entailed repetitive administration of test sera to post-hypoxic polycythemic mice in divided doses [12 s.c. injections of 0.5 ml of serum at 6 h intervals for 3 days; total dose = 6 ml of serum/mouse]. The erythropoietin detection limit was .simeq. 20 IU/l of serum. In mice which received pooled serum from .alpha.Ni3S2-treated rats, erythrocyte 59Fe-uptake averaged 28% [SD .+-. 5] [vs. 3.7 .+-. 1.1% in control rats; P < 0.001]. Based on a 7 point calibration plot, the erythropoietin activity in pooled serum from .alpha.Ni3S2-treated rats averaged 130 IU/l [SD .+-. 18] [vs. 27 .+-. 6 IU/l in control rats; P < 0.001]. In vitro addition of Ni[II] to rat serum [100 .mu.g/l] had no effect on serum erythropoietin activity. Induction of erythrocytosis in rats by intrarenal injection of .alpha.Ni3S2 is mediated by increased serum erythropoietin activity.