Author
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Reeves, Phillip |
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Demars, Lana |
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Submitted to: Experimental Biology and Medicine
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 2/1/2005 Publication Date: 4/28/2005 Citation: Reeves, P.G., DeMars, L.C.S. 2005. Repletion of copper-deficient rats with dietary copper restores duodenal hephaestin protein and iron absorption. Experimental Biology and Medicine. 230:320-325. Interpretive Summary: It is important to know the concentration of a mineral nutrient in the diet so we can keep track of how much we consume, and whether it meets the recommended intake. However, we also need to know whether a nutrient is available for absorption. Many factors affect absorption of minerals, and one of the most important ones is the interaction of one mineral with another to the extent that absorption and utilization are reduced or enhanced. We have shown in previous studies that dietary copper deficiency reduces the absorption of iron possibly through a defect in a copper-dependent intestinal enzyme, Hephaestin, which aides Fe transport into the blood. Copper deficiency also hinders the utilization of iron, which leads to anemia. In the current study, we wanted to know whether defects in the iron absorption mechanisms involving Hephaestin could be reversed. The concentration of copper in the diet was less than 0.5 mg/kg diet (deficient copper) in one group and five mg/kg (adequate copper) in another; the amount of iron was 35 mg/kg (adequate) in both groups. The diets were fed to male rats for four weeks, and then copper was refed to some of the copper-deficient rats for another two weeks. Results showed that copper-deficient rats absorbed less iron than copper adequate rats. In addition, the relative amount of intestinal Hephaestin was less in copper-deficient rats, and the copper-deficient rats developed anemia. After the copper-deficient rats had been replenished with copper for one to two weeks, intestinal Hephaestin concentration and Fe absorption rose to values even higher than those in copper-adequate rats, and most signs of anemia were restored to normal values. These findings suggest a strong association between intestinal Hephaestin levels and Fe absorption in the rat, and that reduced iron absorption in these rats is the primary cause of anemia. Technical Abstract: Copper (Cu) deficiency in rats reduces the relative concentrations of duodenal Hephaestin (Hp), reduces the absorption of iron (Fe), and causes anemia. The following experiment was conducted to determine whether dietary Cu repletion would reverse these effects. Three groups of eight rats each were fed a Cu-deficient diet (0.25 mg Cu/kg; CuD) for four weeks. Then the diet of one of these groups was replenished with Cu for another two weeks. Two other groups were fed a Cu-adequate diet (5.0 mg Cu/kg; CuA). At four weeks, one group of CuA and one of CuD rats was fed a single meal labeled with 59Fe, and the amount of label retained was measured one week later by whole-body-counting (WBC). At five weeks, one group each of CuA, CuD, and the Cu replete rats were fed a single meal labeled with 59Fe, and the amount of label retained was measured by WBC one week later. Results showed that CuD rats absorbed less (P<0.05) Fe than CuA rats, the relative amount of duodenal Hp was less (P<0.05) in CuD rats, and the CuD rats developed anemia. After the CuD rats had been replenished with Cu for one week, Fe retention rose to values even higher (P<0.05) than those in CuA rats. After two weeks, the relative amount of Hp in the duodenum was higher than normal, and most signs of anemia were restored to normal values. These findings suggest a strong association between duodenal Hp abundance and Fe absorption in the CuD rat, and that reduced Fe absorption in these rats is the primary cause of anemia. |
