Progressive Increases in Dietary Iron Are Associated with the Emergence of Pathologic Disturbances of Copper Homeostasis in Growing Rats

Ha, Jung‐Heun; Doguer, Caglar; Flores, Shireen; Wang, Tao; Collins, James F.

doi:10.1093/jn/nxx070

Cited by 15 publications

(13 citation statements)

References 33 publications

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“…Therefore, we only reported the results of multiple regression analyses showing significant results. Further, it is known both Cu and iron have similar binding proteins in cerebral tissue and they affect each other during uptake (Fox 2003;Ha et al 2018); therefore, the iron level might affect the present results. To exclude such possibilities, we additionally performed non-whole brain multiple regression analyses including hair iron level as an additional covariate.…”

Section: Statistical Analyses Of Non-whole Brain Analysesmentioning

confidence: 90%

Association of copper levels in the hair with gray matter volume, mean diffusivity, and cognitive functions

et al. 2019

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Although copper plays a critical role in normal brain functions and development, it is known that excess copper causes toxicity. Here we investigated the associations of copper levels in the hair with regional gray matter volume (rGMV), mean diffusivity (MD), and cognitive differences in a study cohort of 924 healthy young adults. Our findings showed that high copper levels were associated mostly with low cognitive abilities (low scores on the intelligence test consisting of complex speed tasks, involving reasoning task, a complex arithmetic task, and a reading comprehension task) as well as lower reverse Stroop interference, high rGMV over widespread areas of the brain [mainly including the bilateral lateral and medial parietal cortices, medial temporal structures (amygdala, hippocampus, and parahippocampal gyrus), middle cingulate cortex, orbitofrontal cortex, insula, perisylvian areas, inferior temporal lobe, temporal pole, occipital lobes, and supplementary motor area], as well as high MD of the right substantia nigra and bilateral hippocampus, which are indicative of low density in brain tissues. These results suggest that copper levels are associated with mostly aberrant cognitive functions, greater rGMV in extensive areas, greater MD (which are indicative of low density in brain tissues) in subcortical structures in the healthy young adults, possibly reflecting copper's complex roles in neural mechanisms.

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Section: Statistical Analyses Of Non-whole Brain Analysesmentioning

confidence: 90%

Association of copper levels in the hair with gray matter volume, mean diffusivity, and cognitive functions

et al. 2019

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“…Hb and Hct in whole blood were measured by standard methods. 53 , 54 Serum ferritin concentration was quantified with the Mouse Ferritin ELISA Kit (ab157713; Abcam). Plasma EPO concentration was measured by Mouse Erythropoietin Quantikine ELISA Kit (MEP00B; R&D Systems).…”

Section: Methodsmentioning

confidence: 99%

“… 54 , 55 TIBC was assessed as previously described. 53 , 54 TSAT was calculated as serum iron/TIBC × 100. Non-heme iron content in tissues was determined using a standard acid digestion, chromogen-based colorimetric assay.…”

Section: Methodsmentioning

confidence: 99%

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Oral Gavage of Ginger Nanoparticle-Derived Lipid Vectors Carrying Dmt1 siRNA Blunts Iron Loading in Murine Hereditary Hemochromatosis

et al. 2019

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Nanoparticles (NPs) have been utilized to deliver drugs to the intestinal epithelium in vivo . Moreover, NPs derived from edible plants are less toxic than synthetic NPs. Here, we utilized ginger NP-derived lipid vectors (GDLVs) in a proof-of-concept investigation to test the hypothesis that inhibiting expression of divalent metal-ion transporter 1 (Dmt1) would attenuate iron loading in a mouse model of hereditary hemochromatosis (HH). Initial experiments using duodenal epithelial organ cultures from intestine-specific Dmt1 knockout (KO) (Dmt1 int/int ) mice in the Ussing chamber established that Dmt1 is the only active iron importer during iron-deficiency anemia. Further, when Dmt1 int/int mice were crossed with mice lacking the iron-regulatory hormone, hepcidin (Hepc −/− ), iron loading was abolished. Hence, intestinal Dmt1 is required for the excessive iron absorption that typifies HH. Additional experiments established a protocol to produce GDLVs carrying functional Dmt1 small interfering RNAs (siRNAs) and to target these gene delivery vehicles to the duodenal epithelium in vivo (by incorporating folic acid [FA]). When FA-GDLVs carrying Dmt1 siRNA were administered to weanling Hepc −/− mice for 16 days, intestinal Dmt1 mRNA expression was attenuated and tissue iron accumulation was blunted. Oral delivery of functional siRNAs by FA-GDLVs is a suitable therapeutic approach to mitigate iron loading in murine HH.

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“…These results confirm a significant influence of Cu on the release of tissue Fe. Ha et al [322] showed that Cu metabolism is impaired when dietary Fe intake is >10 times higher than the normal Fe supply established by WHO. Significantly elevated levels of Fe may result in anemia, likely due to a lack of Cu in the diet [323].…”

Section: Fe Vs Cumentioning

confidence: 99%

The Role of Fe, Zn, and Cu in Pregnancy

2020

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Iron (Fe), copper (Cu), and zinc (Zn) are microelements essential for the proper functioning of living organisms. These elements participatein many processes, including cellular metabolism and antioxidant and anti-inflammatory defenses, and also influence enzyme activity, regulate gene expression, and take part in protein synthesis. Fe, Cu, and Zn have a significant impact on the health of pregnant women and in the development of the fetus, as well as on the health of the newborn. A proper concentration of these elements in the body of women during pregnancy reduces the risk of complications such as anemia, induced hypertension, low birth weight, preeclampsia, and postnatal complications. The interactions between Fe, Cu, and Zn influence their availability due to their similar physicochemical properties. This most often occurs during intestinal absorption, where metal ions compete for binding sites with transport compounds. Additionally, the relationships between these ions have a great influence on the course of reactions in the tissues, as well as on their excretion, which can be stimulated or delayed. This review aims to summarize reports on the influence of Fe, Cu, and Zn on the course of single and multiple pregnancies, and to discuss the interdependencies and mechanisms occurring between Fe, Cu, and Zn.

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Progressive Increases in Dietary Iron Are Associated with the Emergence of Pathologic Disturbances of Copper Homeostasis in Growing Rats

Cited by 15 publications

References 33 publications

Association of copper levels in the hair with gray matter volume, mean diffusivity, and cognitive functions

Association of copper levels in the hair with gray matter volume, mean diffusivity, and cognitive functions

Oral Gavage of Ginger Nanoparticle-Derived Lipid Vectors Carrying Dmt1 siRNA Blunts Iron Loading in Murine Hereditary Hemochromatosis

The Role of Fe, Zn, and Cu in Pregnancy

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