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The effect of copper deficiency on the formation of hemosiderin in sprague-dawley rats

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Abstract

We demonstrated previously that loading iron into ferritin via its own ferroxidase activity resulted in damage to the ferritin while ferritin loaded by ceruloplasmin, a copper-containing ferroxidase, was not damaged and had similar characteristics to native ferritin (Welch et al. (2001) Free Radic Biol Med 31:999–1006). Interestingly, it has been suggested that the formation of hemosiderin, a proposed degradation product of ferritin, is increased in animals deficient in copper. In this study, groups of rats were fed normal diets, copper deficient diets, iron supplemented diets, or copper deficient-iron supplemented diets for 60 days. Rats fed copper-deficient diets had no detectable active serum ceruloplasmin, which indicates that they were functionally copper deficient. There was a significant increase in the amount of iron in isolated hemosiderin fractions from the livers of copper-deficient rats, even more than that found in rats fed only an iron-supplemented diet. Histological analysis showed that copper-deficient rats had iron deposits (which are indicative of hemosiderin) in their hepatocytes and Kupffer cells, whereas rats fed diets sufficient in copper only had iron deposits in their Kupffer cells. Histologic evidence of iron deposition was more pronounced in rats fed diets that were deficient in copper. Additionally, sucrose density-gradient sedimentation profiles of ferritin loaded with iron in vitro via its own ferroxidase activity was found to have similarities to that of the sedimentation profile of the hemosiderin fraction from rat livers. The implications of these data for the possible mechanism of hemosiderin formation are discussed.

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Acknowledgments

The authors thank Terri Maughan for her secretarial assistance in preparation of the manuscript and Kent Udy and Paul Swaner for their assistance with animal husbandry.

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  1. Kevin D. Welch & T. Zane Davis

    Present address: USDA-ARS Poisonous Plant Research Laboratory, Logan, UT, USA

Authors and Affiliations

  1. Biotechnology Center, Utah State University, Logan, UT, 84322–4705, USA

    Kevin D. Welch, Jeffery O. Hall, T. Zane Davis & Steven D. Aust

  2. Center for Integrated BioSystems, Utah State University, Logan, UT, USA

    Kevin D. Welch, T. Zane Davis & Steven D. Aust

  3. Veterinary Diagnostic Laboratory, Utah State University, Logan, UT, USA

    Jeffery O. Hall

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  1. Kevin D. Welch
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Correspondence to Steven D. Aust.

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Welch, K.D., Hall, J.O., Davis, T.Z. et al. The effect of copper deficiency on the formation of hemosiderin in sprague-dawley rats. Biometals 20, 829–839 (2007). https://doi.org/10.1007/s10534-006-9046-7

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  • DOI: https://doi.org/10.1007/s10534-006-9046-7

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