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.

scholarly journals Modulation of intestinal sulfur assimilation metabolism regulates iron homeostasis

2018 ◽  
Vol 115 (12) ◽  
pp. 3000-3005 ◽  
Author(s):  
Benjamin H. Hudson ◽  
Andrew T. Hale ◽  
Ryan P. Irving ◽  
Shenglan Li ◽  
John D. York
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Iron Reduction ◽  
Genetic Basis ◽  
Iron Homeostasis ◽  
Deficiency Anemia ◽  
Sulfur Assimilation ◽  
Nucleotide Hydrolysis ◽  
Evolutionarily Conserved ◽  
Organismal Development

Sulfur assimilation is an evolutionarily conserved pathway that plays an essential role in cellular and metabolic processes, including sulfation, amino acid biosynthesis, and organismal development. We report that loss of a key enzymatic component of the pathway, bisphosphate 3′-nucleotidase (Bpnt1), in mice, both whole animal and intestine-specific, leads to iron-deficiency anemia. Analysis of mutant enterocytes demonstrates that modulation of their substrate 3′-phosphoadenosine 5′-phosphate (PAP) influences levels of key iron homeostasis factors involved in dietary iron reduction, import and transport, that in part mimic those reported for the loss of hypoxic-induced transcription factor, HIF-2α. Our studies define a genetic basis for iron-deficiency anemia, a molecular approach for rescuing loss of nucleotidase function, and an unanticipated link between nucleotide hydrolysis in the sulfur assimilation pathway and iron homeostasis.

scholarly journals Iron supplementation in goitrous, iron-deficient children improves their response to oral iodized oil

2000 ◽  
pp. 217-223 ◽  
Author(s):  
M Zimmermann ◽  
P Adou ◽  
T Torresani ◽  
C Zeder ◽  
R Hurrell
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Iron Supplementation ◽  
Thyroid Volume ◽  
Oral Iron ◽  
Deficiency Anemia ◽  
Urinary Iodine Concentration ◽  
Iodized Oil ◽  
Iron Deficient ◽  
Group 2

OBJECTIVE: In developing countries, many children are at high risk for both goiter and iron-deficiency anemia. Because iron deficiency may impair thyroid metabolism, the aim of this study was to determine if iron supplementation improves the response to oral iodine in goitrous, iron-deficient anemic children. DESIGN: A trial of oral iodized oil followed by oral iron supplementation in an area of endemic goiter in the western Ivory Coast. METHODS: Goitrous, iodine-deficient children (aged 6-12 years; n=109) were divided into two groups: Group 1 consisted of goitrous children who were not anemic; Group 2 consisted of goitrous children who were iron-deficient anemic. Both groups were given 200mg oral iodine as iodized oil. Thyroid gland volume using ultrasound, urinary iodine concentration (UI), serum thyroxine (T(4)) and whole blood TSH were measured at baseline, and at 1, 5, 10, 15 and 30 weeks post intervention. Beginning at 30 weeks, the anemic group was given 60mg oral iron as ferrous sulfate four times/week for 12 weeks. At 50 and 65 weeks after oral iodine (8 and 23 weeks after completing iron supplementation), UI, TSH, T(4) and thyroid volume were remeasured. RESULTS: The prevalence of goiter at 30 weeks after oral iodine in Groups 1 and 2 was 12% and 64% respectively. Mean percent change in thyroid volume compared with baseline at 30 weeks in Groups 1 and 2 was -45.1% and -21.8% respectively (P<0.001 between groups). After iron supplementation in Group 2, there was a further decrease in mean thyroid volume from baseline in the anemic children (-34.8% and -38.4% at 50 and 65 weeks) and goiter prevalence fell to 31% and 20% at 50 and 65 weeks. CONCLUSION: Iron supplementation may improve the efficacy of oral iodized oil in goitrous children with iron-deficiency anemia.

scholarly journals Effects of Iron Deficiency Anemia and Its Rapid Correction on the Serum Metabolomic Profile of Rhesus Infants

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1070-1070
Author(s):  
Brian Sandri ◽  
Gabriele Lubach ◽  
Eric Lock ◽  
Michael Georgieff ◽  
Pamela Kling ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Acid Production ◽  
Iron Status ◽  
Deficiency Anemia ◽  
Iron Dextran ◽  
Metabolomic Profile ◽  
Intramuscular Injections ◽  
Iron Deficient ◽  
Rapid Correction

Abstract Objectives To determine whether rapid correction of iron deficiency using intramuscular iron dextran normalizes serum metabolomic changes in a nonhuman primate model of iron deficiency anemia (IDA). Methods Blood was collected from naturally iron-sufficient (IS; n = 10) and IDA (n = 12) male and female infant rhesus monkeys (Macaca mulatta) at 6 months of age. IDA infants were treated with intramuscular injections of iron dextran, 10 mg/weekly for 4–8 weeks. Iron status was reevaluated following treatment using hematological measurements and sera were metabolically profiled using HPLC/MS with isobaric standards for identification and quantification. Results Early-life iron deficiency anemia negatively affects many cellular metabolic processes, including energy production, electron transport, and oxidative degradation of toxins. Slow iron repletion with dietary supplementation restores iron deficient monkeys from a hematological perspective, but the serum metabolomic profile remains differed from monkeys that had been iron sufficient their entire life. Whether rapid iron restoration through intramuscular injections of iron dextran normalizes serum metabolomic profile is not known. A total of 654 metabolites were measured with differences in 53 metabolites identified between IS and IDA monkeys at 6 months (P 0.05). Pathway analyses provided evidence of altered liver function, hypometabolic state, differential essential fatty acid production, irregular inosine and guanosine metabolism, and atypical bile acid production in IDA infants. After treatment, iron-related hematological parameters had recovered, but the formerly IDA infants remained metabolically distinct from the IS infants, with 225 metabolites differentially expressed between the groups. Conclusions As with slow iron repletion, rapid iron repletion does not normalize the altered serum metabolomic profile in rhesus infants with IDA, suggesting the need for iron supplementation in the pre-anemic stage. Funding Sources National Institutes of Health.

scholarly journals Molecular Aspects and Treatment of Iron Deficiency in the Elderly

2020 ◽  
Vol 21 (11) ◽  
pp. 3821
Author(s):  
Antonino Davide Romano ◽  
Annalisa Paglia ◽  
Francesco Bellanti ◽  
Rosanna Villani ◽  
Moris Sangineto ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Iron Homeostasis ◽  
Diagnostic Algorithm ◽  
The Elderly ◽  
Deficiency Anemia ◽  
Clinical State ◽  
Ageing Population ◽  
Gastrointestinal Lesions ◽  
Aged Subjects

Iron deficiency (ID) is the most frequent nutritional deficiency in the whole population worldwide, and the second most common cause of anemia in the elderly. The prevalence of anemia is expecting to rise shortly, because of an ageing population. Even though WHO criteria define anemia as a hemoglobin serum concentration <12 g/dL in women and <13 g/dL in men, several authors propose different and specific cut-off values for the elderly. Anemia in aged subjects impacts health and quality of life, and it is associated with several negative outcomes, such as longer time of hospitalization and a higher risk of disability. Furthermore, it is an independent risk factor of increased morbidity and mortality. Even though iron deficiency anemia is a common disorder in older adults, it should be not considered as a normal ageing consequence, but a sign of underlying dysfunction. Relating to the molecular mechanism in Iron Deficiency Anemia (IDA), hepcidin has a key role in iron homeostasis. It downregulates the iron exporter ferroportin, inhibiting both iron absorption and release. IDA is frequently dependent on blood loss, especially caused by gastrointestinal lesions. Thus, a diagnostic algorithm for IDA should include invasive investigation such as endoscopic procedures. The treatment choice is influenced by the severity of anemia, underlying conditions, comorbidities, and the clinical state of the patient. Correction of anemia and iron supplementation should be associated with the treatment of the causal disease.

scholarly journals Eye-Blinking Rates Are Slower in Infants with Iron-Deficiency Anemia than in Nonanemic Iron-Deficient or Iron-Sufficient Infants

2010 ◽  
Vol 140 (5) ◽  
pp. 1057-1061 ◽  
Author(s):  
Betsy Lozoff ◽  
Rinat Armony-Sivan ◽  
Niko Kaciroti ◽  
Yuezhou Jing ◽  
Mari Golub ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Deficiency Anemia ◽  
Iron Deficient

scholarly journals Effect of Maternal Iron Deficiency Anemia on the Iron Store of Newborns in Ethiopia

Anemia ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Betelihem Terefe ◽  
Asaye Birhanu ◽  
Paulos Nigussie ◽  
Aster Tsegaye
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Serum Ferritin ◽  
Complete Blood Count ◽  
Iron Status ◽  
Hemoglobin Concentration ◽  
Deficiency Anemia ◽  
Iron Store ◽  
Cross Sectional ◽  
Iron Deficient

Iron deficiency anemia among pregnant women is a widespread problem in developing countries including Ethiopia, though its influence on neonatal iron status was inconsistently reported in literature. This cross-sectional study was conducted to compare hematologic profiles and iron status of newborns from mothers with different anemia status and determine correlation between maternal and neonatal hematologic profiles and iron status in Ethiopian context. We included 89 mothers and their respective newborns and performed complete blood count and assessed serum ferritin and C-reactive protein levels from blood samples collected from study participants. Maternal median hemoglobin and serum ferritin levels were 12.2 g/dL and 47.0 ng/mL, respectively. The median hemoglobin and serum ferritin levels for the newborns were 16.2 g/dL and 187.6 ng/mL, respectively. The mothers were classified into two groups based on hemoglobin and serum ferritin levels as iron deficient anemic (IDA) and nonanemic (NA) and newborns of IDA mothers had significantly lower levels of serum ferritin (P=0.017) and hemoglobin concentration (P=0.024). Besides, newborns’ ferritin and hemoglobin levels showed significant correlation with maternal hemoglobin (P=0.018;P=0.039) and ferritin (P=0.000;P=0.008) levels. We concluded that maternal IDA may have an effect on the iron stores of newborns.

scholarly journals Iron-deficiency anemia from matriptase-2 inactivation is dependent on the presence of functional Bmp6

Blood ◽  
2011 ◽  
Vol 117 (2) ◽  
pp. 647-650 ◽  
Author(s):  
Anne Lenoir ◽  
Jean-Christophe Deschemin ◽  
Léon Kautz ◽  
Andrew J. Ramsay ◽  
Marie-Paule Roth ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Iron Overload ◽  
Serine Protease ◽  
Iron Deficiency Anemia ◽  
Iron Homeostasis ◽  
Deficiency Anemia ◽  
Hepatic Iron ◽  
Master Regulator ◽  
Liver Iron ◽  
The Relationship

Abstract Hepcidin is the master regulator of iron homeostasis. In the liver, iron-dependent hepcidin activation is regulated through Bmp6 and its membrane receptor hemojuvelin (Hjv), whereas, in response to iron deficiency, hepcidin repression seems to be controlled by a pathway involving the serine protease matriptase-2 (encoded by Tmprss6). To determine the relationship between Bmp6 and matriptase-2 pathways, Tmprss6−/− mice (characterized by increased hepcidin levels and anemia) and Bmp6−/− mice (exhibiting severe iron overload because of hepcidin deficiency) were intercrossed. We showed that loss of Bmp6 decreased hepcidin levels; increased hepatic iron; and, importantly, corrected hematologic abnormalities in Tmprss6−/− mice. This finding suggests that elevated hepcidin levels in patients with familial iron-refractory, iron-deficiency anemia are the result of excess signaling through the Bmp6/Hjv pathway.

scholarly journals Role of red cell distribution width (RDW) in the detection of iron deficiency anaemia in pregnancy within the first 20 weeks of gestation

1970 ◽  
Vol 37 (3) ◽  
pp. 102-105 ◽  
Author(s):  
GS Sultana ◽  
SA Haque ◽  
T Sultana ◽  
Q Rahman ◽  
ANN Ahmed
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Red Cell Distribution Width ◽  
Deficiency Anemia ◽  
Mean Corpuscular Hemoglobin ◽  
Red Cell ◽  
Cell Distribution ◽  
Corpuscular Hemoglobin ◽  
Distribution Width ◽  
Iron Deficient

Iron deficiency anemia is common problem during pregnancy. Red cell size variation (anisocytosis) is the earliest morphologic changes in iron deficiency anemia. Red cell distribution width is a quantitative measure of red cell size variation and it can give the idea of early iron deficiency before other test to become positive.190 pregnant women were included in this study. Red cell distribution width was compared between iron deficient & non-iron deficient pregnant women. Red cell distribution width also compared with Hb level, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration and peripheral blood film in prelatent iron deficiency, latent iron deficiency, mild and moderate iron deficiency anemia. Red cell distribution width had sensitivity 82.3% and specificity 97.4%. Whereas Hb level, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration and peripheral blood film all had 56.6%, 29.2%, 68.1%, 15% and 38.9% sensitivity but specificity was 90.9%, 98.7%, 83.1%, 96.1% and 98.7% in the detection of iron deficiency. Red cell distribution width appears to be a reliable and useful parameter for detection of iron deficiency during pregnancy. DOI: http://dx.doi.org/10.3329/bmrcb.v37i3.9122 BMRCB 2011; 37(3): 102-105

scholarly journals Hematologic Effects of Levothyroxine in Iron-Deficient Subclinical Hypothyroid Patients: A Randomized, Double-Blind, Controlled Study

2009 ◽  
Vol 94 (1) ◽  
pp. 151-156 ◽  
Author(s):  
Hakan Cinemre ◽  
Cemil Bilir ◽  
Feyzi Gokosmanoglu ◽  
Talat Bahcebasi
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Subclinical Hypothyroidism ◽  
Serum Iron ◽  
Oral Iron ◽  
Iron Therapy ◽  
Deficiency Anemia ◽  
Controlled Study ◽  
Iron Group ◽  
Iron Deficient

Abstract Context: In patients with coexisting iron-deficiency anemia and subclinical hypothyroidism, anemia does not adequately respond to oral iron therapy. Objective: We studied whether iron-deficiency anemia might indicate treatment of subclinical hypothyroidism. Design: Patients were assigned to a control or experimental group: 240 mg/d oral iron alone (iron group) or 240 mg/d oral iron plus 75 μg/d levothyroxine (iron/levothyroxine group). Levels of hemoglobin, hematocrit, red blood cell count, serum iron levels, ferritin, total iron-binding capacity, TSH, and free T4 were measured before and after treatment. Setting: The study was conducted at a university hospital outpatient clinic. Patients: Fifty-one patients with coexisting iron-deficiency anemia and subclinical hypothyroidism participated in the study. Intervention: Patients were treated as described above in either the iron group or the iron/levothyroxine group. Main Outcome Measure: A clinically satisfactory increase in hemoglobin was regarded as successful. Results: Mean hemoglobin levels increased by 0.4 g/dl in the iron group [95% confidence interval (CI) 0.2–0.7, P = 0.001], whereas it increased by a mean of 1.9 g/dl in the iron/levothyroxine group (95% CI 1.5–2.3, P &lt; 0.0001). The increase in serum iron was greater in the iron/levothyroxine group by a mean of 47.6 μg/dl (95% CI 34.5–60.6, P &lt; 0.0001). Increases in hemoglobin, red blood cells, hematocrit, and serum ferritin levels after treatment were statistically significantly greater in the iron/levothyroxine group (P &lt; 0.0001). Starting hemoglobin and increase in hemoglobin were negatively correlated in the iron/levothyroxine group (r = −0.531, P = 0.006). Conclusions: Subclinical hypothyroidism should be treated in iron-deficiency anemia patients when both conditions coexist. This would provide a desired therapeutic response to oral iron replacement and prevent ineffective iron therapy.

scholarly journals THE EFFECT OF IRON DEFICIENCY ANEMIA ON GLYCATED HEMOGLOBIN (HBA1C) IN NON DIABETIC ADULTS

2019 ◽  
Vol 3 (8) ◽  
Author(s):  
Dr. Suman Choudhary ◽  
Dr. Sukh Dev Choudhary ◽  
Dr. Himanshi Choudhary ◽  
Dr. Ronak Gandhi
Keyword(s):  
Iron Deficiency ◽  
Iron Deficiency Anemia ◽  
Deficiency Anemia ◽  
Diabetic Patients ◽  
Glucose Levels ◽  
Uncontrolled Diabetes ◽  
Iron Deficient ◽  
Healthy Control ◽  
Sugar Levels ◽  
Hba1c Levels

Background: Iron deficiency anemia is the most common form of anemia in India. Hemoglobin A1c (HbA1c) is used in diabetic patients as an index of glycemic control reflecting glucose levels of the previous 3 months. Like blood sugar levels, HbA1c levels are also affected by the presence of variant hemoglobins, hemolytic anemias, nutritional anemias, uremia, pregnancy, and acute blood loss. Previous studies suggest that iron deficiency anemia (IDA) affects the levels of HbA1c. Methods: A prospective observational study on 50 iron deficiency patient cases and 50 healthy control. Exclusion and inclusion criteria were used to recruit cases from the wards and OPDs of the hospital. Appropriate descriptive statistics was used to analyse the data. Results: The HbA1C was significantly higher in the iron deficiency patients as compare to the control (5.88 ± 0.41 vs 5.03 ± 0.17, respectively, P < .05). Conclusion: Our results showed that iron deficiency was associated with higher proportions of HbA1c, which could cause problems in the diagnosis of uncontrolled diabetes mellitus in iron-deficient patients. Keywords: Non-Diabetic Patient, Glycosylated Haemoglobin, Iron Deficiency Anaemia.

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