Interactions among nickel, copper, and iron in rats

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Abstract
In two fully-crossed, three-way, two-by-three-by-three, factorially arranged experiments, female weanling rats were fed a basal diet supplemented with iron at 15 and 45 μg/g, nickel at 0, 5, and 50 μg/g, and copper at either 0, 0.5, and 5 μ/g (Expt. 1) or 0, 0.25, and 12 μg/g (Expt. 2) A gram of basal diet contained in Expt. 1 approximately 16 ng of nickel, 2.3 μg of iron, and 0.47 μg of copper; and in Expt. 2, 20 ng of nickel, 1.3 μg of iron, and 0.39 μg of copper. Expt. 1 was terminated at 11 weeks, and Expt. 2 at 8 weeks because, at those times, some rats fed no supplemental copper and the high level of nickel began to lose weight, or die from heart rupture. The findings demonstrated that relationships are complex among nickel, copper, and iron. Nickel interacted with copper and this interaction was influenced by dietary iron. Signs of copper deficiency were more severe when nickel was supplemented to the diet provided that copper deprivation was neither very severe nor mild. Iron deprivation apparently enhanced the antagonism by exacerbating copper deficiency. Signs of copper deficiency that were made more severe by nickel supplementation were depressed weight gain (Expt. 2), hematocrit (Expt. 1), hemoglobin, and plasma alkaline phosphatase activity; and elevated ratios of heart wt/body wt, kidney wt/body wt, and liver wt/body wt. Because nickel and copper have similar physical and chemical properties, the interactions between those two elements were probably the result, of isomorphous replacement of copper by nickel at various functional sites that interfered with some biological processes.