EFFECTS OF NICKEL ON EPO PRODUCTION
Almost 40 years ago the group of Hopfer discovered that the intra-renal injection of nickel compounds (αNi3S2, NiO, NiS2, βNiS, Ni dust) produces an increase in circulating EPO and erythrocytosis in rats (6). The intra-renal injection of Ni3S2 was also effective in guinea pigs but not in in hamsters or gerbils, indicating significant species-specificity (18). Importantly, NiCl2 proved to increase EPO mRNA expression and EPO production in the human hepatoma cell line, Hep3B (5). The intraperitoneal infusion of NiCl2 failed to stimulate EPO production in rats (17). Likewise, the subcutaneous injection of nickel failed to stimulate renal EPO mRNA expression in mice (10).
Note, here, that dietary nickel was found to increase the blood hemoglobin concentration and to cause pulmonary hypertension in broiler chickens (12). No such effect has been reported with respect to increased nickel supplementation in mammals. It can be stated that the effect of Ni2+ differs from that of Co2+, as the latter clearly stimulates EPO synthesis and erythropoiesis following oral administration (7).