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Anemia, Iron Storage and Ceruloplasmin in Copper Nutrition in the Growing Rat^1,2,3,

Departments of Animal Sciences and Nutrition, Rutgers University, New Brunswick, New Jersey 08903

Several studies have shown that copper-deficient animals accumulate iron as anemia persists, indicating the unavailability of absorbed iron for hemoglobin formation. Recently, it was suggested that ceruloplasmin by its ferroxidase activity is the regulating agent that mobilizes the iron from cells to plasma. This experiment was conducted to examine in vivo this suggestion by the periodic monitoring of the levels of liver iron and copper and hemoglobin in relation to ceruloplasmin oxidase activity during a state of copper depletion and subsequent repletion. A total of 230 weanling rats were divided into two groups and fed either a low copper (<1 ppm) or a control diet (35 ppm copper as CuCO₃). Both diets contained 135 ppm iron as Fe₂O₃. After 42 days half the rats on the low copper diet were fed the control diet and continued for another 42 days of repletion. Animals were killed at weekly intervals for 84 days and on days 44 and 47. Hemoglobin, hematocrit, plasma ceruloplasmin oxidase activity, liver iron and liver copper were different (P < 0.05) from the control values starting at day 7 of depletion. Ceruloplasmin activity was reduced to 5% of the control by day 14 of depletion, and an accumulation of iron in the liver amounted to 65% more than the control values by the end of the 42-day depletion period. Hemoglobin and hematocrit values were reduced to 50% of the control values during this period. With copper repletion the marked increase in ceruloplasmin oxidase activity (25-fold in 2 days) corresponded with the rapid removal of iron (30% decrease in 2 days) and the accumulation of copper in the liver. Further increases in the ceruloplasmin activity in the repleted animals were tied with the corresponding removal of iron from the liver during repletion. These changes were followed by a steady increase in hemoglobin and hematocrit values equalling the control values by days 70 and 63 of repletion, respectively. These results are compatible with the suggestion that copper exerts its influence in the metabolism of hemoglobin through ceruloplasmin by mobilizing the absorbed iron, bound to transferrin, from the cells to the plasma.

KEY WORDS: • copper depletion-repletion • ceruloplasmin-ferroxidase • anemia • liver iron

¹ Paper of the Journal Series, New Jersey Agricultural Experiment Station, Rutgers University, New Brunswick, N. J. 08903.

² Preliminary report of these results was presented at the Federation of American Societies for Experimental Biology, Chicago, Ill. 1971, Federation Proc. 30: 461 (abstr.).

³ Assistance with the statistical analyses was provided by Dr. J. R. Trout.

⁴ Present address is Department of Pathology, UCLA School of Medicine, Los Angeles, Calif.

Manuscript received 10 March 1972.

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