Copper supplementation reverses dietary iron overload-induced pathologies in mice
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Dosyalar
Tarih
2018
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Elsevier Science Inc
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Dietary iron overload in rodents impairs growth and causes cardiac hypertrophy, serum and tissue copper depletion, depression of serum ceruloplasmin (Cp) activity and anemia. Notably, increasing dietary copper content to similar to 25-fold above requirements prevents the development of these physiological perturbations. Whether copper supplementation can reverse these high-iron-related abnormalities has, however, not been established. The current investigation was thus undertaken to test the hypothesis that supplemental copper will mitigate negative outcomes associated with dietary iron loading. Weanling mice were thus fed AIN-93G-based diets with high (>100-fold in excess) or adequate (similar to 80 ppm) iron content. To establish the optimal experimental conditions, we first defined the time course of iron loading, and assessed the impact of supplemental copper (provided in drinking water) on the development of high-iron-related pathologies. Copper supplementation (20 mg/L) for the last 3 weeks of a 7-week high-iron feeding period reversed the anemia, normalized serum copper levels and Cp activity, and restored tissue copper concentrations. Growth rates, cardiac copper concentrations and heart size, however, were only partially normalized by copper supplementation. Furthermore, high dietary iron intake reduced intestinal Cu-64 absorption (similar to 60%) from a transport solution provided to mice by oral, intragastric gavage. Copper supplementation of iron-loaded mice enhanced intestinal Cu-64 transport, thus allowing sufficient assimilation of dietary copper to correct many of the noted high-iron-related physiological perturbations. We therefore conclude that high- iron intake increases the requirement for dietary copper (to overcome the inhibition of intestinal copper absorption). (C) 2018 Elsevier Inc. All rights reserved.
Açıklama
Anahtar Kelimeler
Anemia, Cardiac hypertrophy, Ceruloplasmin, Intestine, Copper absorption, Dietary iron loading, Peroxidation In-Vivo, Stable-Isotope Cu-65, Young Men, Deficiency, Rats, Metabolism, Absorption, Retention, Cells
Kaynak
Journal of Nutritional Biochemistry
WoS Q Değeri
Q1
Scopus Q Değeri
Q1
Cilt
59
