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Article

Dietary Iron Intake in Excess of Requirements Impairs Intestinal Copper Absorption in Sprague Dawley Rat Dams, Causing Copper Deficiency in Suckling Pups

by 1,†, 2,3,† and 1,*
1
Food Science and Human Nutrition Department, University of Florida, Gainesville, FL 32611, USA
2
Research Center for Industrialization of Natural Neutralization, Dankook University, Cheonan 31116, Korea
3
Department of Food Science and Nutrition, Dankook University, Cheonan 31116, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Math P. Cuajungco, Maria C. Linder and Marcelo E. Tolmasky
Biomedicines 2021, 9(4), 338; https://doi.org/10.3390/biomedicines9040338
Received: 7 February 2021 / Revised: 13 March 2021 / Accepted: 23 March 2021 / Published: 27 March 2021
(This article belongs to the Special Issue Zinc and Copper in Human Health and Disease)
Physiologically relevant iron-copper interactions have been frequently documented. For example, excess enteral iron inhibits copper absorption in laboratory rodents and humans. Whether this also occurs during pregnancy and lactation, when iron supplementation is frequently recommended, is, however, unknown. Here, the hypothesis that high dietary iron will perturb copper homeostasis in pregnant and lactating dams and their pups was tested. We utilized a rat model of iron-deficiency/iron supplementation during pregnancy and lactation to assess this possibility. Rat dams were fed low-iron diets early in pregnancy, and then switched to one of 5 diets with normal (1×) to high iron (20×) until pups were 14 days old. Subsequently, copper and iron homeostasis, and intestinal copper absorption (by oral, intragastric gavage with 64Cu), were assessed. Copper depletion/deficiency occurred in the dams and pups as dietary iron increased, as evidenced by decrements in plasma ceruloplasmin (Cp) and superoxide dismutase 1 (SOD1) activity, depletion of hepatic copper, and liver iron loading. Intestinal copper transport and tissue 64Cu accumulation were lower in dams consuming excess iron, and tissue 64Cu was also low in suckling pups. In some cases, physiological disturbances were noted when dietary iron was only ~3-fold in excess, while for others, effects were observed when dietary iron was 10–20-fold in excess. Excess enteral iron thus antagonizes the absorption of dietary copper, causing copper depletion in dams and their suckling pups. Low milk copper is a likely explanation for copper depletion in the pups, but experimental proof of this awaits future experimentation. View Full-Text
Keywords: iron supplementation; ceruloplasmin; pregnancy; lactation; SOD1 iron supplementation; ceruloplasmin; pregnancy; lactation; SOD1
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MDPI and ACS Style

Lee, J.K.; Ha, J.-H.; Collins, J.F. Dietary Iron Intake in Excess of Requirements Impairs Intestinal Copper Absorption in Sprague Dawley Rat Dams, Causing Copper Deficiency in Suckling Pups. Biomedicines 2021, 9, 338. https://doi.org/10.3390/biomedicines9040338

AMA Style

Lee JK, Ha J-H, Collins JF. Dietary Iron Intake in Excess of Requirements Impairs Intestinal Copper Absorption in Sprague Dawley Rat Dams, Causing Copper Deficiency in Suckling Pups. Biomedicines. 2021; 9(4):338. https://doi.org/10.3390/biomedicines9040338

Chicago/Turabian Style

Lee, Jennifer K.; Ha, Jung-Heun; Collins, James F. 2021. "Dietary Iron Intake in Excess of Requirements Impairs Intestinal Copper Absorption in Sprague Dawley Rat Dams, Causing Copper Deficiency in Suckling Pups" Biomedicines 9, no. 4: 338. https://doi.org/10.3390/biomedicines9040338

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