Nickel influences iron metabolism through physiologic, pharmacologic and toxicologic mechanisms in the rat.

A study involving three experiments was done to ascertain whether the beneficial effect of nickel on hematopoiesis in moderately iron-deficient rats was due to physiologic and/or pharmacologic mechanisms. Female Sprague-Dawley rats were fed nickel supplements ranging from 0 to 100 micrograms/g in iron-low (15 micrograms Fe3+/g), iron-adequate (65 micrograms Fe3+/g), or iron-luxuriant (100 micrograms Fe3+/g) diets. The basal diet contained from 2 ng (experiment 3) to 36 ng (experiment 1) of nickel/g. At 10 weeks, both nickel deficiency and toxicity (100 micrograms/g diet) tended to depress hematopoiesis and markedly altered femur and liver trace element content in marginally iron-deficient rats. The alterations included elevated copper, iron and nickel, and depressed calcium and manganese in femurs. The pharmacologic action of nickel was indicated by the finding that high dietary nickel (5, 10, 20 or 50 micrograms/g) apparently stimulated hematopoiesis in marginally iron-deprived rats to a greater extent than dietary levels of nickel (0.1, 0.5 or 1.0 microgram/g) considered adequate for nutritional needs. High dietary nickel also elevated the iron content in liver of marginally iron-adequate rats. The findings indicate that nickel influences iron metabolism at physiologic, pharmacologic and toxic levels of intake. They also indicate that many previously reported signs of nickel deprivation, including effects on hematopoiesis, may have been misinterpreted and might be manifestations of pharmacologic actions of nickel.