scholarly journals Relationship between Down-Regulation of Copper-Related Genes and Decreased Ferroportin Protein Level in the Duodenum of Iron-Deficient Piglets

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 104
Author(s):  
Aneta Jończy ◽  
Rafał Mazgaj ◽  
Rafał Radosław Starzyński ◽  
Piotr Poznański ◽  
Mateusz Szudzik ◽  
...  
Keyword(s):  
Iron Absorption ◽  
Underlying Mechanism ◽  
Metabolic Effects ◽  
Deficiency Anemia ◽  
Copper Transporter ◽  
Cellular Iron ◽  
Iron Deficient ◽  
Copper Distribution ◽  
Iron Deposits ◽  
Neonatal Iron Deficiency

In mammals, 2 × 1012 red blood cells (RBCs) are produced every day in the bone marrow to ensure a constant supply of iron to maintain effective erythropoiesis. Impaired iron absorption in the duodenum and inefficient iron reutilization from senescent RBCs by macrophages contribute to the development of anemia. Ferroportin (Fpn), the only known cellular iron exporter, as well as hephaestin (Heph) and ceruloplasmin, two copper-dependent ferroxidases involved in the above-mentioned processes, are key elements of the interaction between copper and iron metabolisms. Crosslinks between these metals have been known for many years, but metabolic effects of one on the other have not been elucidated to date. Neonatal iron deficiency anemia in piglets provides an interesting model for studying this interplay. In duodenal enterocytes of young anemic piglets, we identified iron deposits and demonstrated increased expression of ferritin with a concomitant decline in both Fpn and Heph expression. We postulated that the underlying mechanism involves changes in copper distribution within enterocytes as a result of decreased expression of the copper transporter—Atp7b. Obtained results strongly suggest that regulation of iron absorption within enterocytes is based on the interaction between proteins of copper and iron metabolisms and outcompetes systemic regulation.

Comparison of Apical and Basolateral Cu Treatment for Iron-related Gene Regulation During Deferoxamine Induced Iron Deficiency Anemia

2021 ◽  
Author(s):  
Ezgi Evcan ◽  
sukru gulec
Keyword(s):  
Tissue Culture ◽  
Gene Regulation ◽  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Iron Homeostasis ◽  
Deficiency Anemia ◽  
Copper Transporter ◽  
Culture Plate ◽  
Iron Deficient ◽  
Basolateral Side

Abstract Background: Intestinal copper transporter (Atp7a) mutant brindled mice with systemic Cu deficiency had elevated Cu levels in enterocyte cells without any perturbation of iron regulating genes, suggesting that blood Cu level might be important for intestinal iron homeostasis during iron deficiency anemia (IDA). We hypothesized that the blood Cu level and polarization (apical and basolateral) of enterocyte cells might be important regulators for the compensatory response on the regulation of genes in enterocyte cells during IDA. Methods: We grew Caco-2 cells on a bicameral cell culture plate to mimic the human intestine system and on a regular tissue culture plate. IDA was induced by Deferoxamine (DFO). The cells were treated with Cu and Cu with Fe following mRNA expressions of DMT1, FPN, TFR, and ANKRD37 were analyzed. Results: Our main finding was that basolateral treatment of Cu significantly reduced mRNA expressions of iron-regulated genes, including DMT1, FPN, TFR, and ANKRD37, compared to DFO treated and DFO with apical Cu treated groups in both bicameral and regular tissue culture plates. Conclusions: Cu level in the basolateral side of Caco-2 cells significantly influenced the intracellular gene regulation in DFO induced iron-deficient condition, and polarization of the cells might be important factor gene regulation in enterocyte cells.

Iron absorption in normal and iron-deficient beagle dogs: mucosal iron kinetics

1985 ◽  
Vol 249 (4) ◽  
pp. G439-G448 ◽  
Author(s):  
M. H. Nathanson ◽  
A. Muir ◽  
G. D. McLaren
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Iron Uptake ◽  
Iron Absorption ◽  
Whole Body ◽  
Deficiency Anemia ◽  
Beagle Dogs ◽  
Storage Pool ◽  
Fractional Rate ◽  
Iron Deficient

Absorption of dietary iron requires uptake of iron by the brush border of the intestinal epithelial cells, intracellular transport, and transfer to the systemic circulation. In iron-deficiency anemia, iron absorption is greatly increased, but the individual steps responsible for this increase have not been identified. We have developed a method to evaluate the rate constants for each of these steps, and we report here our results in beagle dogs a) under normal conditions and b) after phlebotomy to produce iron-deficiency anemia. Simultaneous administration of oral 59Fe3+-citrate and intravenous 55Fe-transferrin was used to investigate the kinetics of mucosal iron transport. Plasma levels of both isotopes and the whole-body excretion pattern of 59Fe were monitored sequentially, and the fractional mucosal transport rates were estimated by nonlinear least-squares fit of a physiologically based mathematical model to these data. Under normal conditions the fractional rate of mucosal iron uptake from the intestinal lumen was rate limiting, being less than 1% of the fractional rate of either iron incorporation into the mucosal storage pool or transfer of iron from the mucosa to the plasma. After induction of iron-deficiency anemia, the fractional mucosal iron uptake rate increased sixfold (P less than 0.005), while the rate of incorporation into the mucosal storage pool decreased ninefold (P less than 0.02); in contrast, the fractional rate of iron transfer to the plasma did not change. These results indicate that the enhanced iron absorption in iron-deficiency anemia is attributable to an increase in mucosal iron available for transfer to the plasma, leading in turn to a net increase in iron absorption, despite a normal fractional transfer rate.

Proton Pump Inhibitor Use and the Ability to Replete Iron Stores

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1039-1039
Author(s):  
Alina M Huang ◽  
Christine M Ho ◽  
John L. Reagan ◽  
Eric Winer
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Proton Pump ◽  
Iron Absorption ◽  
Oral Iron ◽  
Deficiency Anemia ◽  
Care Clinic ◽  
Iron Stores ◽  
Iron Deficient ◽  
Iron Replacement

Abstract Abstract 1039 Background: Oral iron absorption occurs in the duodenum and requires increased gastric acidity to allow iron to remain in the more soluble, ferrous form. Many patients with iron deficiency anemia who require oral iron repletion are on proton pump inhibitors (PPIs) for management of various conditions that require acid suppression for treatment. In vitro studies suggest that inhibition of gastric acid secretion decreases the bioavailability of iron. In patients with established iron deficiency anemia who are on PPIs, there is a paucity of data regarding the efficacy of iron replacement with concomitant PPI use. Sharma et al. published a case report on 2 patients who were iron deficient and on PPI therapy (Sharma et. al. Southern Medical Journal 2004). Their findings showed that discontinuation of the PPI resulted in improvement of iron deficiency anemia on the same dose of oral iron replacement. Additionally, Hutchinson et al. demonstrated that in individuals with hereditary hemachromatosis, those on PPIs had a significant reduction in phlebotomy requirements needed to keep serum ferritin ∼50μg (Hutchinson et. al. Gut 2007). We conducted a retrospective study to assess whether a difference exists in terms of iron repletion between patients on a PPI versus those not on a PPI. Methods: Patients were selected from the medical primary care clinic from charts dating January 2000 until January 2009. Included patients were adults older than 18 years of age, a diagnosis of iron deficiency based on ferritin < 30 with at least one follow up ferritin value, and recipients of oral iron replacement. Excluded patients were those with chronic active bleeding and anemia of chronic disease. Indices examined include iron (Fe), total iron binding capacity (TIBC), ferritin, transferrin saturation, hemoglobin (Hb), hematocrit (Hct), and mean corpuscular volume (MCV). The primary endpoint of interest is repletion of iron stores defined by ferritin > 30. Those who were able to replete their iron stores are termed “responders” and those who were not are termed “nonresponders”. Results: Forty-five patients have been identified who have met the above criteria. Of these patients, 14 were on a PPI and 31 were not on a PPI. Of the patients not on a PPI, 38.7% responded to oral iron. Of the patients on a PPI, 50.0% responded to oral iron. The average initial and final values of indices of interest were compared between the groups (Table 1). Discussion: Our data suggests that patients both on and off PPIs show the ability to replete their iron stores. Furthermore, it appears that a slightly greater percentage of patients on a PPI compared with those not on a PPI are able to replete their iron stores, though the numbers remain small. Most importantly, these findings challenge the commonly held belief that PPI use impairs oral iron absorption. A prospective study is warranted to further confirm these observational data. Disclosures: No relevant conflicts of interest to declare.

scholarly journals New findings on iron absorption conditioning factors

2004 ◽  
Vol 4 (3) ◽  
pp. 241-248 ◽  
Author(s):  
Rute Cândida Pereira ◽  
Alcides da Silva Diniz ◽  
Luiz Oscar Cardoso Ferreira
Keyword(s):  
Iron Absorption ◽  
The Body ◽  
Vulnerable Groups ◽  
Deficiency Anemia ◽  
Public Health Issue ◽  
Conditioning Factors ◽  
Risk Increase ◽  
New Findings ◽  
Intake Regulation ◽  
The Impact

The authors focus iron intake regulation in the body and the probable mechanisms related to iron absorption. They analyze the impact of iron absorption deficiency resulting in iron deficiency anemia, a public health issue of great impact in the world influencing child and maternal health risk increase. This paper aims at highlighting the problems affecting the uptake or inhibiting processes of iron absorption in an attempt to correlate information on conditioning factors and current findings. This study is a document based descriptive study comprising literature review. In food, iron has different forms, such as the heme and non-heme forms following different absorption pathways with different efficiency rates, depending on conditioning factors, such as diet profile, physiological aspects, iron chemical state, absorption regulation, transportation, storing, excretion and the presence of disease, They also discuss the current difficulties in dealing with iron nutritional deficiency in vulnerable groups, children and pregnant women, and focus data on iron consumption, adhesion to breast feeding and the frequency of prenatal care visits.

Maturation, iron deficiency, and ligands in enteric radioiron transport in vitro

1963 ◽  
Vol 204 (1) ◽  
pp. 171-175 ◽  
Author(s):  
W. S. Ruliffson ◽  
J. M. Hopping
Keyword(s):  
Ascorbic Acid ◽  
Iron Deficiency ◽  
Iron Absorption ◽  
Deficiency Anemia ◽  
Anaerobic Incubation ◽  
Reverse Effect ◽  
Factors Affecting ◽  
Everted Gut Sac

The effects in rats, of age, iron-deficiency anemia, and ascorbic acid, citrate, fluoride, and ethylenediaminetetraacetate (EDTA) on enteric radioiron transport were studied in vitro by an everted gut-sac technique. Sacs from young animals transported more than those from older ones. Proximal jejunal sacs from anemic animals transported more than similar sacs from nonanemic rats, but the reverse effect appeared in sacs formed from proximal duodenum. When added to media containing ascorbic acid or citrate, fluoride depressed transport as did anaerobic incubation in the presence of ascorbic acid. Anaerobic incubation in the presence of EDTA appeared to permit elevated transport. Ascorbic acid, citrate, and EDTA all enhanced the level of Fe59 appearing in serosal media. These results appear to agree with previously established in vivo phenomena and tend to validate the in vitro method as one of promise for further studies of factors affecting iron absorption and of the mechanism of iron absorption.

scholarly journals IRON ABSORPTION AND RESPONSE TO ORAL IRON THERAPY IN IRON DEFICIENCY ANEMIA ASSOCIATED TO ASYMPTOMATIC GIARDIASIS.

1993 ◽  
Vol 33 (6) ◽  
pp. 661-661
Author(s):  
Helena U Suzuki ◽  
Mauro B Morais ◽  
Jose N Corral ◽  
Ulisses Fagundes-Neto ◽  
Nelson L Machado
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Iron Absorption ◽  
Oral Iron ◽  
Iron Therapy ◽  
Deficiency Anemia ◽  
Oral Iron Therapy

scholarly journals Consumption of a Double-Fortified Salt Affects Perceptual, Attentional, and Mnemonic Functioning in Women in a Randomized Controlled Trial in India

2017 ◽  
Vol 147 (12) ◽  
pp. 2297-2308 ◽  
Author(s):  
Michael J Wenger ◽  
Laura E Murray-Kolb ◽  
Julie EH Nevins ◽  
Sudha Venkatramanan ◽  
Gregory A Reinhart ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Iron Status ◽  
Controlled Trial ◽  
Reproductive Age ◽  
Deficiency Anemia ◽  
Control Group ◽  
Attention And Memory ◽  
Double Blind ◽  
Iron Deficient ◽  
Mnemonic Function

Abstract Background: Iron deficiency and iron deficiency anemia have been shown to have negative effects on aspects of perception, attention, and memory. Objective: The purpose of this investigation was to assess the extent to which increases in dietary iron consumption are related to improvements in behavioral measures of perceptual, attentional, and mnemonic function. Methods: Women were selected from a randomized, double-blind, controlled food-fortification trial involving ad libitum consumption of either a double-fortified salt (DFS) containing 47 mg potassium iodate/kg and 3.3 mg microencapsulated ferrous fumarate/g (1.1 mg elemental Fe/g) or a control iodized salt. Participants' blood iron status (primary outcomes) and cognitive functioning (secondary outcomes) were assessed at baseline and after 10 mo at endline. The study was performed on a tea plantation in the Darjeeling district of India. Participants (n = 126; 66% iron deficient and 49% anemic at baseline) were otherwise healthy women of reproductive age, 18–55 y. Results: Significant improvements were documented for iron status and for perceptual, attentional, and mnemonic function in the DFS group (percentage of variance accounted for: 16.5%) compared with the control group. In addition, the amount of change in perceptual and cognitive performance was significantly (P < 0.05) related to the amount of change in blood iron markers (mean percentage of variance accounted for: 16.0%) and baseline concentrations of blood iron markers (mean percentage of variance accounted for: 25.0%). Overall, there was evidence that the strongest effects of change in iron status were obtained for perceptual and low-level attentional function. Conclusion: DFS produced measurable and significant improvements in the perceptual, attentional, and mnemonic performance of Indian female tea pickers of reproductive age. This trial was registered at clinicaltrials.gov as NCT01032005.

scholarly journals Unexpected Link between Iron and Drug Resistance of Candida spp.: Iron Depletion Enhances Membrane Fluidity and Drug Diffusion, Leading to Drug-Susceptible Cells

2006 ◽  
Vol 50 (11) ◽  
pp. 3597-3606 ◽  
Author(s):  
Tulika Prasad ◽  
Aparna Chandra ◽  
Chinmay K. Mukhopadhyay ◽  
Rajendra Prasad
Keyword(s):  
Multidrug Resistance ◽  
Membrane Fluidity ◽  
Iron Uptake ◽  
Efflux Pump ◽  
Disulfonic Acid ◽  
Candida Spp ◽  
Copper Transporter ◽  
Iron Depletion ◽  
Cellular Iron ◽  
Increased Sensitivity

ABSTRACT Inthis study, we show that iron depletion in Candida albicans with bathophenanthrolene disulfonic acid and ferrozine as chelators enhanced its sensitivity to several drugs, including the most common antifungal, fluconazole (FLC). Several other species of Candida also displayed increased sensitivity to FLC because of iron restriction. Iron uptake mutations, namely,Δ ftr1 and Δftr2, as well as the copper transporter mutation Δccc2, which affects high-affinity iron uptake in Candida, produced increased sensitivity to FLC compared to that of the wild type. The effect of iron depletion on drug sensitivity appeared to be independent of the efflux pump proteins Cdr1p and Cdr2p. We found that iron deprivation led to lowering of membrane ergosterol by 15 to 30%. Subsequently, fluorescence polarization measurements also revealed that iron-restricted Candida cells displayed a 29 to 40% increase in membrane fluidity, resulting in enhanced passive diffusion of the drugs. Northern blot assays revealed that the ERG11 gene was considerably down regulated in iron-deprived cells, which might account for the lowered ergosterol content. Our results show a close relationship between cellular iron and drug susceptibilities of C. albicans. Considering that multidrug resistance is a manifestation of multifactorial phenomena, the influence of cellular iron on the drug susceptibilities of Candida suggests iron as yet another novel determinant of multidrug resistance.

scholarly journals Reply: Intravenous Ferumoxytol in Pediatric Patients With Iron-Deficiency Anemia

2017 ◽  
Vol 51 (12) ◽  
pp. 1146-1146
Author(s):  
Nabil E. Hassan
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Pediatric Patients ◽  
Iron Absorption ◽  
Deficiency Anemia

Iron Deficiency in children is common problem. Its mechanism could be nutritional or due to lack of iron absorption. Several conditions are associated with IDA. Presence of inflammation further complicate attempts to make a definitive diagnoses or accurately quantify reponse to therapy.

Hepatic glucose production and insulin sensitivity and responsiveness in iron-deficient anemic rats

1993 ◽  
Vol 264 (3) ◽  
pp. E380-E390 ◽  
Author(s):  
M. J. Borel ◽  
J. L. Beard ◽  
P. A. Farrell
Keyword(s):  
Insulin Sensitivity ◽  
Hepatic Glucose Production ◽  
Insulin Dose ◽  
Glucose Production ◽  
Deficiency Anemia ◽  
Response Curves ◽  
Iron Deficient ◽  
Hepatic Glucose ◽  
Basal Plasma ◽  
Insulin Responsiveness

We performed euglycemic hyperinsulinemic glucose clamps at insulin infusion rates of 1.9, 4.0, 9.3, and 19.3 mU.kg-1 x min-1 in rats with varying severities of iron deficiency anemia (IDA; mean hemoglobin concentrations of 59, 79, 107, and 137 g/l) to assess the effect of IDA on insulin sensitivity and responsiveness. Glucose appearance and disappearance (Rd) rates were determined using a primed continuous infusion of [3-3H]glucose. Basal plasma glucose and insulin concentrations were similar between the IDA and control rats. Basal hepatic glucose production was significantly (P = 0.0001) elevated in the two most anemic groups (13.6 +/- 2.4 and 12.6 +/- 3.1 vs. 10.6 +/- 2.2 and 10.2 +/- 2.0 mg.kg-1 x min-1). A significant upward shift in the insulin dose-response curves for Rd indicated an increase in peripheral insulin responsiveness in the two most anemic groups while a slight leftward shift was suggestive of an increase in insulin sensitivity in all three anemic groups. Hepatic insulin sensitivity and responsiveness were unaffected by IDA. We conclude that increased glucose utilization rates in IDA rats are due primarily to an increase in peripheral insulin responsiveness.

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