Effects of Varying Dietary Iron on the Expression of Copper Deficiency in the Growing Rat: Anemia, Ferroxidase I and II, Tissue Trace Elements, Ascorbic Acid, and Xanthine Dehydrogenase

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Abstract
The effect of dietary iron on the development of copper-deficiency anemia in the growing rat was investigated. For up to 80 d, female rats (75 g) were fed purified diets containing adequate, marginal or low levels of iron, and either 0.7 or 10 ppm copper. Hemoglobin levels and factors postulated to affect liver iron mobilization, including ferroxidase (Fox) I and II, ascorbate and liver xanthine dehydrogenase (XDH) were assayed. By d 7, Fox I activity in the copper-deficient groups was 10% that of the copper-sufficient groups; thereafter, Fox I activity remained low, and was not affected by dietary iron. Fox II activity in the copper-deficient groups after d 28 was 50–75% of values from rats adequate in copper. On d 49, hemoglobin levels in the copper-deficient groups were lower than in the copper-sufficient groups fed low and marginal levels of iron, but were similar to those fed adequate iron. Liver iron was similar in both groups fed adequate iron, but was higher in the copper-deficient than in the copper-sufficient rats fed low or marginal levels of iron. Copper deficiency tended to result in slightly lower ascorbate levels on d 80 at all levels of iron. Liver XDH activity tended to be lower in the copper-deficient groups than in the copper-sufficient groups on d 28 and 49. These results show that copper deficiency may impair liver iron mobilization in the growing rat if dietary iron is low. Possible mechanisms include decreased Fox activity and/or decreased iron reduction by ascorbate or XDH.