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Copper supplementation in drinking water reverses dietary iron overload‐induced anemia and cardiac hypertrophy in mice
Author(s) -
Wang Tao,
Xiang Ping,
Ha JungHeun,
Doguer Caglar,
Wang Xiaoyu,
Flores Shireen,
Kang Y. James,
Collins James F.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.750.16
Subject(s) - weanling , anemia , medicine , copper deficiency , hemoglobin , endocrinology , hematocrit , copper , muscle hypertrophy , iron deficiency anemia , chemistry , organic chemistry
Our previous studies showed that high‐iron (0.88% carbonyl iron) diet feeding of mice and rats lead to impaired growth, severe anemia, tissue copper depletion and cardiac hypertrophy. 1,2 Interestingly, these pathophysiological perturbations were prevented by addition of extra copper to the high Fe diet, indicating the role of copper deficiency in the pathogenesis. The current study was undertaken to test the hypothesis that dietary copper supplementation to Fe overload mice could restore systemic copper status, and reverse the anemia and cardiac hypertrophy. Weanling, male C57BL/6 mice were fed AIN‐93G‐based diets containing adequate (~8 ppm) Cu in combination with adequate (~80 ppm) or high (~8000 ppm) Fe for 4 weeks. Then, the mice were given 20 mg/L Cu (as Cu sulfate) in drinking water for another 3 weeks. Subsequently, the iron and copper‐related phenotype of the mice was assessed. High‐Fe diet fed mice showed a significant growth impairment and systemic Cu deficiency, accompanied by severe anemia, decreased serum ceruloplamine (Cp) activity and cardiac hypertrophy. Cu replenishment via drinking water corrected the deficits in hemoglobin (Hb), hematocrit (HCT) and serum Cp levels, restored tissue Cu status, and reversed cardiac hypertrophy. It was further found that high‐Fe feeding significantly impaired intestinal Cu absorption, and disturbed Cu tissue distribution. This study demonstrates that high Fe consumption blocks intestinal Cu absorption, leading to a systemic Cu deficiency which resulted in a severe anemia and cardiac hypertrophy in mice. Cu supplementation corrects these physiologic perturbations. These observations provided further evidence of physiologically‐relevant iron‐copper interactions in mammals. Support or Funding Information Supported by NIH grant 1R01 DK074867 (to J.F.C.). This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .