Studies on Growth, Copper Metabolism and Iron Metabolism of Rats Fed High Levels of Zinc

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Abstract
Young rats were fed purified diets containing high levels of zinc (0.75 and 1.0%) in the presence and absence of various combinations of copper, iron, vitamin and liver extract supplements. Under these conditions effects of zinc toxicity on growth, hemoglobin formation, liver copper and iron levels, and heart cytochrome oxidase activity were observed in several experiments. The factor(s) of liver extract that alleviates the subnormal growth of zinc-fed rats appears to reside primarily in the organic portion of the extract. There is an indication that certain vitamins, such as vitamin B12 and folic acid, may be involved. The data suggest that the active principle can be extracted from the liver with methanol. In addition to supporting the accepted hypothesis that zinc interferes with copper metabolism, results of this study indicate that zinc directly interferes with iron metabolism. Supplements of iron had no apparent effect on the heart cytochrome oxidase activities of rats on a high zinc diet indicating that copper is the important factor connected with restoration of the enzyme activity. Results of an isotope experiment suggest that zinc interferes with copper metabolism by decreasing the utilization and increasing the excretion of copper in the rat, but apparently has little effect on the absorption of copper. Results of another isotope experiment indicate that zinc does not interfere with the absorption of iron, but interferes, in some manner, with the utilization of iron. Throughout this entire study, the addition of zinc to the diet resulted in a marked increase in liver zinc. None of the dietary components tested counteracted this tremendous increase in the accumulation of zinc in the liver.