Iron supplementation by intraperitoneal injection eliminates the accumulation of hepatic copper induced by excess calcium in rats

Abstract

Excess calcium is well known to induce iron deficiency. Furthermore, excess calcium increases hepatic copper concentration and decreases renal copper concentration. We investigated the effect of iron supplementation on the tissue distribution of copper in rats given a high-calcium diet. Male rats (5 weeks old) were divided into four groups; a control group, and three groups given a diet containing 5-fold higher calcium than its requirement and an intraperitoneal iron supplementation of 0, 1 or 2 mg/week as iron dextran. The animals were fed their respective experimental diets with or without iron supplementation for 4 weeks. Although the high-calcium diet had no effect on calcium concentrations in the liver, kidney, testis, spleen and plasma, it reduced haematocrit and iron concentrations in the liver, kidney and testis and the rats had a moderate iron deficiency. The iron supplementation restored to normal these signs of iron deficiency. The high-calcium diet increased hepatic copper concentration but decreased plasma copper concentration and ceruloplasmin activity, which was restored by the iron supplementation. The copper concentration in bile was neither affected by the high-calcium diet nor the iron supplementation. The high-calcium diet decreased the copper concentration in the kidney, which was not restored by the iron supplementation. These results suggest that secondary iron deficiency stimulates hepatic accumulation of copper in rats given excess calcium by suppressing copper efflux into the circulation. The reduced renal copper concentration by excess calcium is independent of the iron deficiency.