scholarly journals Supplemental Microalgal Iron Helps Replete Blood Hemoglobin in Moderately Anemic Mice Fed a Rice-Based Diet

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2239
Author(s):  
Rohil S. Bhatnagar ◽  
Dennis D. Miller ◽  
Olga I. Padilla-Zakour ◽  
Xin Gen Lei
Keyword(s):  
Heme Iron ◽  
Deficiency Anemia ◽  
Free Access ◽  
Mrna Levels ◽  
Divalent Metal Transporter 1 ◽  
Minute Amount ◽  
Divalent Metal Transporter ◽  
Non Heme Iron ◽  
Blood Hemoglobin ◽  
Iron Deficient

Iron deficiency anemia affects 1.2 billion people globally. Our objectives were to determine if (1) supplemental iron extracted from defatted microalgae (Nannochloropsis oceanica, DGM) and (2) a combination of minute amount of plant phytase and inulin could help replete hemoglobin in anemic mice. Mice (7 weeks old) were fed a control diet (6 mg Fe/kg). After 10 weeks, the mice were assigned to three treatments: control, control + DGM iron (Fe-DGM, 39 mg Fe/kg), or control + 1% inulin + 250 units of phytase/kg (INU−PHY, 6 mg Fe/kg). The mice had free access to diets and water for 6 weeks. The Fe-DGM group had elevated blood hemoglobin (p < 0.01) and a two-fold greater (p < 0.0001) liver non-heme iron over the control. Strikingly, the INU-PHY group had 34% greater non-heme iron than the control, despite the same concentrations of iron in their diets. Fe-DGM group had altered (p < 0.05) mRNA levels of hepcidin, divalent metal transporter 1, transferrin and transferrin receptor 1. Iron extracted from defatted microalgae seemed to be effective in alleviating moderate anemia, and INU-PHY enhanced utilization of intrinsic iron present in the rice diet. Our findings may lead to a novel formulation of these ingredients to develop safer and bioavailable iron supplements for iron-deficient populations.

Pharmacokinetics of pulmonary manganese absorption: evidence for increased susceptibility to manganese loading in iron-deficient rats

2005 ◽  
Vol 288 (5) ◽  
pp. L887-L893 ◽  
Author(s):  
Elizabeth Heilig ◽  
Ramon Molina ◽  
Thomas Donaghey ◽  
Joseph D. Brain ◽  
Marianne Wessling-Resnick
Keyword(s):  
Iron Deficiency ◽  
Iron Absorption ◽  
Iron Status ◽  
Mrna Levels ◽  
Blood Clearance ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Pulmonary Uptake ◽  
Iron Deficient ◽  
Metal Absorption

High levels of airborne manganese can be neurotoxic, yet little is known about absorption of this metal via the lungs. Intestinal manganese uptake is upregulated by iron deficiency and is thought to be mediated by divalent metal transporter 1 (DMT1), an iron-regulated factor known to play a role in dietary iron absorption. To better characterize metal absorption from the lungs to the blood and test whether iron deficiency may modify this process, the pharmacokinetics of pulmonary manganese and iron absorption by control and iron-deficient rats were compared. Levels of DMT1 expression in the lungs were determined to explore potential changes induced by iron deficiency that might alter metal absorption. The pharmacokinetic curves for intratracheally instilled54Mn and59Fe were significantly different, suggesting that pulmonary uptake of the two metals involves different mechanisms. Intratracheally instilled iron-deficient rats had significantly higher blood54Mn levels, whereas blood59Fe levels were significantly reduced compared with controls. The same trend was observed when radioisotopes were delivered by intravenous injection, indicating that iron-deficient rats have altered blood clearance of manganese. In situ analysis revealed the presence of DMT1 transcripts in airway epithelium; however, mRNA levels did not change in iron deficiency. Although lung DMT1 levels and metal absorption did not appear to be influenced by iron deficiency, the differences in blood clearance of instilled manganese identified by this study support the idea that iron status can influence the potential toxicity of this metal.

Adaptive changes of duodenal iron transport proteins in celiac disease

2004 ◽  
Vol 17 (3) ◽  
pp. 316-325 ◽  
Author(s):  
Donatella Barisani ◽  
Antonina Parafioriti ◽  
Maria Teresa Bardella ◽  
Heinz Zoller ◽  
Dario Conte ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Iron Deficiency ◽  
Protein Expression ◽  
Iron Transport ◽  
Basolateral Membrane ◽  
Deficiency Anemia ◽  
Mrna Levels ◽  
Divalent Metal Transporter 1 ◽  
Iron Stores ◽  
Iron Deficient

Iron deficiency is a manifestation of celiac disease (CD) usually attributed to a decreased absorptive surface, although no data on the regulation of iron transport under these conditions are currently available. Our aim was to evaluate divalent metal transporter 1 (DMT1), duodenal cytochrome b (Dcytb), ferroportin 1 (FP1), hephaestin, and transferrin receptor 1 (TfR1) expression, as well as iron regulatory protein (IRP) activity in duodenal biopsies from control, anemic, and CD patients. We studied 10 subjects with dyspepsia, 6 with iron-deficiency anemia, and 25 with CD. mRNA levels were determined by real-time PCR, protein expression by Western blotting or immunohistochemistry, and IRP activity by gel shift assay. Our results showed that DMT1, FP1, hephaestin, and TfR1 mRNA levels were significantly increased in CD patients with reduced body iron stores compared with controls, similar to what was observed in anemic patients. Protein expression paralleled the mRNAs changes. DMT1 protein expression was localized in differentiated enterocytes at the villi tips in controls, whereas with iron deficiency it was observed throughout the villi. FP1 expression was localized on the basolateral membrane of enterocytes and increased with low iron stores. TfR1 was localized in the crypts in controls but also in the villi with iron deficiency. These changes were paralleled by IRP activity, which increased in all iron-deficient subjects. We conclude that duodenal DMT1, FP1, hephaestin, and TfR1 expression and IRP activity, thus the iron absorption capacity, are upregulated in CD patients as a consequence of iron deficiency, whereas the increased enterocyte proliferation observed in CD has no effect on iron uptake regulation.

scholarly journals Increased DMT1 and FPN1 expression with enhanced iron absorption in ulcerative colitis human colon

2020 ◽  
Vol 318 (2) ◽  
pp. C263-C271 ◽  
Author(s):  
Emily A. Minor ◽  
Justin T. Kupec ◽  
Andrew J. Nickerson ◽  
Karthikeyan Narayanan ◽  
Vazhaikkurichi M. Rajendran
Keyword(s):  
Ulcerative Colitis ◽  
Iron Deficiency ◽  
Iron Absorption ◽  
Basolateral Membrane ◽  
Specific Inhibitor ◽  
Distal Colon ◽  
Human Colon ◽  
Deficiency Anemia ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter

Iron deficiency anemia is a common complication of ulcerative colitis (UC) that can profoundly impact quality of life. Most iron absorption occurs in the duodenum via divalent metal transporter 1 (DMT1)-mediated uptake and ferroportin-1 (FPN1)-mediated export across the apical and basolateral membranes, respectively. However, the colon also contains iron transporters and can participate in iron absorption. Studies have shown increased duodenal DMT1 and FPN1 in patients with UC, but there is conflicting evidence about whether expression is altered in UC colon. We hypothesized that expression of colonic DMT1 and FPN1 will also increase to compensate for iron deficiency. Quantitative RT-PCR and Western blot analyses were performed on duodenal and colonic segmental (right colon, transverse colon, left colon, and rectum) biopsies obtained during colonoscopy. DMT1 mRNA and protein abundances in colonic segments were approximately equal to those in the duodenum, whereas colonic FPN1 mRNA and protein abundances of colonic segments were about one-quarter of those of the duodenum. DMT1 specific mRNA and protein abundances were increased twofold, whereas FPN1 mRNA and protein expressions were increased fivefold in UC distal colon. Immunofluorescence studies revealed enhanced expression of apical membrane- and basolateral membrane-localized DMT1 and FPN1 in UC human colon, respectively. Increased DMT1 expression was associated with enhanced 2-(3-carbamimidoylsulfanylmethyl-benzyl)-isothiourea (CISMBI, DMT1 specific inhibitor)-sensitive 59Fe uptake in UC human colon. We conclude from these results that patients with active UC have increased expression of colonic iron transporters and increased iron absorption, which may be targeted in the treatment of UC-related anemia.

Relationship between intestinal iron-transporter expression, hepatic hepcidin levels and the control of iron absorption

2002 ◽  
Vol 30 (4) ◽  
pp. 724-726 ◽  
Author(s):  
G.J. Anderson ◽  
D. M. Frazer ◽  
S.J. Wilkins ◽  
E. M. Becker ◽  
K. N. Millard ◽  
...  
Keyword(s):  
Iron Transport ◽  
Iron Absorption ◽  
Negative Regulator ◽  
Deficient Diet ◽  
Divalent Metal Transporter 1 ◽  
Intestinal Iron Absorption ◽  
Divalent Metal Transporter ◽  
Hepcidin Expression ◽  
Iron Deficient ◽  
Transport Molecules

Hepcidin is an anti-microbial peptide predicted to be involved in the regulation of intestinal iron absorption. We have examined the relationship between the expression of hepcidin in the liver and the expression of the iron-transport molecules divalent-metal transporter 1, duodenal cytochrome b, hephaestin and Ireg1 in the duodenum of rats switched from an iron-replete to an iron-deficient diet or treated to induce an acute phase response. In each case, elevated hepcidin expression correlated with reduced iron absorption and depressed levels of iron-transport molecules. These data are consistent with hepcidin playing a role as a negative regulator of intestinal iron absorption.

scholarly journals Manganese source affects manganese transport and gene expression of divalent metal transporter 1 in the small intestine of broilers

2011 ◽  
Vol 108 (2) ◽  
pp. 267-276 ◽  
Author(s):  
Shi-Ping Bai ◽  
Lin Lu ◽  
Rui-Lian Wang ◽  
Lin Xi ◽  
Li-Yang Zhang ◽  
...  
Keyword(s):  
Small Intestine ◽  
Control Diet ◽  
Divalent Metal ◽  
Mrna Levels ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Metal Transporter ◽  
Proximal Small Intestine ◽  
Hepatic Portal Vein ◽  
Hepatic Portal

In the present study, two experiments were conducted to investigate the effect of Mn source on Mn transport and the expression of a Mn transporter, divalent metal transporter 1 (DMT1), in the small intestine of broilers. In Expt 1, in situ ligated duodenal loops from Mn-deficient chicks (29-d-old) were perfused with solutions containing 0–8·74 mmol Mn/l from either MnSO4, or one of two organic chelates of Mn and amino acids with moderate (OM) or strong (OS) chelation strength (Qf) up to 30 min. In Expt 2, Mn-deficient intact broilers (14-d-old) were fed a control diet (12·45 mg Mn/kg) or the control diet supplemented with 100 mg Mn/kg as one of all Mn sources for 14 d. The uptake kinetics of Mn from different Mn sources in the ligated duodenal loops followed a saturable process as determined by regression analysis of concentration-dependent uptake rates. The maximum transport rate (Jmax) and Km values, and DMT1 mRNA levels in the ligated duodenal loops were higher (P < 0·01) for OM and OS than for MnSO4. DMT1 mRNA levels were much higher (P < 0·01) in the duodenum than in the jejunum and ileum. Both DMT1 mRNA levels in the duodenum and plasma Mn contents from the hepatic portal vein of intact chicks on day 14 post-feeding increased (P < 0·05) in the following order: control < MnSO4 < OM < OS. These results indicated that organic Mn sources with stronger Qf showed higher Mn transport and absorption, and DMT1 might be involved in the regulation of organic Mn transport in the proximal small intestine of broilers.

scholarly journals Expression of Duodenal Iron Transporter Proteins in Diabetic Patients with and without Iron Deficiency Anemia

2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
Efrat Broide ◽  
Ram Reifen ◽  
Shay Matalon ◽  
Zipi Berkovich ◽  
Haim Shirin
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Iron Transport ◽  
Deficiency Anemia ◽  
Diabetic Patients ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Transporter Proteins ◽  
Group A ◽  
Group B

The role of iron transport proteins in the pathogenesis of anemia in patients with diabetes mellitus (T2DM) is still unclear. We investigated the expression of duodenal transporter proteins in diabetic patients with and without iron deficiency anemia (IDA). Methods. Overall, 39 patients were included: 16 with T2DM and IDA (group A), 11 with T2DM without IDA (group B), and 12 controls (group C). Duodenal mucosal expression of divalent metal transporter 1 (DMT1), ferroportin 1 (FPN), hephaestin (HEPH), and transferrin receptor 1 (TfR) was evaluated by Western blotting. Chronic disease activity markers were measured as well. Results. FPN expression was increased in group A compared to group B and controls: 1.17 (0.72–1.46), 0.76 (0.53–1.04), and 0.71 (0.64–0.86), respectively (p=0.011). TfR levels were over expressed in groups A and B compared to controls: 0.39 (0.26–0.61), 0.36 (0.24–0.43), and 0.18 (0.16–0.24), respectively, (p=0.004). The three groups did not differ significantly with regard to cellular HEPH and DMT1 expression. The normal CRP and serum ferritin levels, accompanied with normal FPN among diabetic patients without IDA, do not support the association of IDA with chronic inflammatory state. Conclusion. In patients with T2DM and IDA, duodenal iron transport protein expression might be dependent on body iron stores rather than by chronic inflammation or diabetes per se.

scholarly journals Iron Deficiency Anemia Caused By Malabsorption from Proton Pump Inhibition

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 962-962
Author(s):  
Michael Boxer
Keyword(s):  
Iron Deficiency ◽  
Ferric Iron ◽  
Intravenous Iron ◽  
Heme Iron ◽  
Deficiency Anemia ◽  
Non Heme Iron ◽  
Clear Explanation ◽  
Iv Iron ◽  
Gastric Parietal Cells ◽  
Iron Replacement

Introduction: Iron deficiency anemia (IDA) not responding to oral iron replacement usually requires a hematologic evaluation. 48 patients taking a proton pump inhibitor (PPI) and not responding to oral iron replacement were found to have an elevated serum gastrin (SG). No patient had gastrointestinal bleeding, gastric resection, bariatric surgery, or menorrhagia. Other causes for iron malabsorption such as celiac disease or helicobacter infection were not present. 94 percent responded to intravenous iron (IV iron). Methods: All patients previously had undergone diagnostic gastrointestinal evaluations. Testing for celiac disease and helicobacter infection was negative. Gastric biopsies did not demonstrate atrophy. Most referrals were from gastroenterologists. Results: 94% responded to IV iron with a rise in their hemoglobin of &gt;/= 2 grams per cent. 83 percent (40/48) were women. Iron dextran (ID) at a fixed dose of 825 mgm was given to 85% of the patients. Twelve of these 41 patients were given a second infusion of ID as the first dose did not produce a satisfactory response. Ferric carboxymaltose and ferumoxytol were each given once at the fixed recommended dose, and second infusions was not necessary. Four patients received iron sucrose at a weight based dose, and a second series of infusions were not necessary. One patient responded to ferumoxytol after a suboptimal response to iron dextran. An elevated SG was defined as &gt;100 pg/mL. The average SG was 370.25 pg/mL (114 to 2101 pg/mL). Hemoglobin rose an average of 3.35 gram% (9.56 to 12.91 gm%). The change in hemoglobin was minus 0.4 to plus 7.0 gm% with a baseline hemoglobin ranging between 6.6 to 14.3 gm% and rising between 9.3 to 16.2 gram%. Ferritin rose an average of 14.8 to 158 ng/mL with baseline ferritin ranging between 3 to 73 ng/mL and rising between 22 to 659 ng/mL The average MCV rose from 75.89 to 84.93 fL with baseline MCV ranging between 61 to 93 fL rising between 69 to 96 fL The average iron saturation rose from 7.49 to 22.89% with baseline saturation ranging between 2 to 34% and rising between 10 to 39%. Discussion: Dietary iron consists of both heme and non heme iron. Heme iron is derived from the hemoglobin and myoglobin in animal food sources such as meat, seafood, and poultry. Heme iron is in the ferrous (II) oxidation state, is easily absorbable, and contributes 10% or somewhat more of total absorbed iron. Non heme iron is in the ferric (III) form and is derived from plants and iron fortified food. Normally 1-2 mgm of iron is absorbed daily. Heme iron is well absorbed after its release by pancreatic enzymes. Non heme iron is less well absorbed and requires acid secretion from gastric parietal cells for the denaturing of ingested proteins and subsequent proteolysis. PPI causes decreased hydrogen ion (H+) production by inhibiting the hydrogen/potassium pump within gastric parietal cells. The elevated SG derives from G cell hyperplasia as a response to the lowered H+ activity caused by PPI. The decreased H+ activity inhibits the release of ferric iron from non animal sources. Iron absorption occurs in the proximal duodenum through the action of a brush border ferrireductase such as duodenal cytochrome B which reduces ferric iron to ferrous iron. With less ferric iron available for reduction less ferrous iron is absorbed, and iron deficiency results. Intravenous iron fully corrected the IDA in 94% of treated patients. Two of the 3 non responders were obese and only received one infusion of ID. Perhaps a second infusion might have been beneficial. However no relation between weight, response, and ID dosing could be detected. Both patients had normal hemoglobins before the iron infusion but were very symptomatic from their iron deficiency. Both patients experienced a rise in their hemoglobin (1.9 gram% and 1.4 gm%). The third non responder actually had a fall in the hemoglobin from 10.5 to 10.1 gm%. No clear explanation was apparent. No clear explanation for the female predominance was apparent. Conclusion: In 2009 119 million prescriptions for PPI were written in the USA. The gastrointestinal literature suggests that anemia from PPI is uncommon. Very likely IDA due to IM from PPI is much more common than recognized and should be considered for any iron deficient patients without evidence for other causes for IDA. Intravenous iron is highly effective. Disclosures No relevant conflicts of interest to declare.

DMT1 Expression Is Regulated by DMT1 Associated Protein (DAP) in K562 Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2661-2661
Author(s):  
Yasumasa Okazaki ◽  
Hong Yin ◽  
Yuxiang Ma ◽  
Emiko Okazaki ◽  
Mary Yeh ◽  
...  
Keyword(s):  
Mitochondrial Protein ◽  
Protoporphyrin Ix ◽  
K562 Cells ◽  
Benzodiazepine Receptor ◽  
Mrna Levels ◽  
Intracellular Iron ◽  
Divalent Metal Transporter 1 ◽  
Divalent Metal Transporter ◽  
Excess Iron ◽  
C Terminus

Abstract While iron is essential for cell growth and survival excess iron through oxidative stress may produce hepatitic cirrhosis and hepatocellular carcinoma, diabetes mellitus, and cardiomyopathy. Iron is absorbed across the duodenum with transport across the brush border mediated by DMT1 and across the basolateral surface by ferroportin with mechanisms that are inversely regulated by body iron concentrations. We have identified in rat intestine DAP, a novel protein that binds to the C-terminus of DMT1 (IRE) but not to the C-terminus of the non-IRE isoform (Blood, Nov 2004; 104: 53). DAP is a 526 amino acid protein that has been previously described as binding to the peripheral benzodiazepine receptor, an intrinsic mitochondrial protein involved in steriodogenesis and possibly in protoporphyrin IX transport into the mitochrondria. To investigate if DAP may have a role in regulation of intracellular iron transport DAP expression was down regulated using a vector containing a siRNA for DAP transfected into K562 cells by electroporation. Expression levels of DAP, transferrin receptor 1 (TfR1), divalent metal transporter 1 (DMT1) and ferritin were examined by western blot and quantitative quantitivative PCR assays from days 1 to 6 after transfection. Following transfection with the DAP siRNA DAP mRNA levels were decreased 50% by day 1 with DAP protein levels decreasing by 50% at day 3. The DAP siRNA also decreased DMT1 protein expression by about 50% for the DMT1 (IRE) protein but had no effect on the protein derived from the non-IRE isoform. The leels of DMT1 mRNA were not affected by DAP siRNA. The decrease of DAP expression was not associated with any change in TfR1 or ferritin expression, suggesting that altered levels of DAP did not affect intracellular iron pools. Transfection with the DAP siRNA resulted also in more protean effects decreasing cell proliferation, the transition from S-phase to G2 in cell cycle, and protein synthesis. These data are consistent with DAP regulating DMT1 expression in K562 cells by modulating turnover of DMT1 (IRE) protein and also having more global effects on cellular metabolism.

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