scholarly journals Iron deficiency affects early stages of embryonic hematopoiesis but not the endothelial to hematopoietic transition

2018 ◽  
Author(s):  
Maya Shvartsman ◽  
Saygin Bilican ◽  
Christophe Lancrin
Keyword(s):  
Iron Deficiency ◽  
Iron Status ◽  
Embryonic Stem ◽  
Experimental System ◽  
Iron Chelator ◽  
Ammonium Citrate ◽  
Ferric Ammonium Citrate ◽  
Hematopoietic Progenitors ◽  
Early Embryonic Stage ◽  
Ferric Ammonium

AbstractIron is an essential micronutrient for hematopoiesis and previous research suggested that iron deficiency in the pregnant female could cause anemia in the offspring. Since the development of all embryonic and adult blood cells begins in the embryo, we aimed to resolve the role of iron in embryonic hematopoiesis. For this purpose, we used an experimental system of mouse embryonic stem cells differentiation into embryonic hematopoietic progenitors. We modulated the iron status in cultures by adding either an iron chelator DFO for iron deficiency, or ferric ammonium citrate for iron excess, and followed the emergence of developing hematopoietic progenitors by flow cytometry. We found interestingly that iron deficiency by DFO did not block the endothelial to hematopoietic transition, the first step of hematopoiesis. However, it had a differential effect on the proliferation, survival and clonogenic capacity of hematopoietic progenitors. Surprisingly, iron deficiency affected erythro-myeloid Kitpos CD41+ progenitors significantly more than the primitive erythroid Kitneg CD41+. The Kitpos progenitors paradoxically died more, proliferated less and had more reduction in colony formation than Kitneg after 24 hours of DFO treatment. Kitpos progenitors expressed less transferrin-receptor on the cell surface and had less labile iron compared to Kitneg, which could reduce their capacity to compete for scarce iron and survive iron deficiency. We suggest that iron deficiency could disturb hematopoiesis already at an early embryonic stage by compromising survival, proliferation and differentiation of definitive hematopoietic progenitors.

Chemicals That Stimulate Iron Uptake – A Novel Approach to Treatment of Iron Deficiency,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3180-3180
Author(s):  
Zhen Li
Keyword(s):  
Iron Deficiency ◽  
Small Molecules ◽  
Iron Uptake ◽  
Iron Absorption ◽  
K562 Cells ◽  
Divalent Metal ◽  
Ammonium Citrate ◽  
Ferric Ammonium Citrate ◽  
Caco2 Cells ◽  
Ferric Ammonium

Abstract 3180 Iron (Fe) is an essential nutrient required for all cells, especially for erythrocyte hemoglobin synthesis which requires absorption of 1–2 mg of iron from the gastrointestinal tract. Iron deficiency as a result of inadequate dietary uptake has multiple consequences including anemia and abnormal neurologic development in children and is a global public health concern. Enterocytes in the duodenum, the site of iron absorption, can extract about 10% of dietary Fe. Nonetheless for numerous reasons simple iron supplementation has not solved the worldwide epidemic of iron deficiency. We hypothesized that small molecules which could potentiate iron uptake into cells would allow enterocytes to absorb an increased amount of dietary iron and could be beneficial in limiting iron deficiency. To identify molecules that would accelerate Fe uptake we used a high through-put screening system in conjunction with a reporter system of K562 cells loaded with the divalent metal chelator calcein whose fluorescence is quenched with chelation of Fe2+. Small molecules that stimulated Fe uptake were defined as causing increased calcein fluorescence quenching compared to Fe alone. K562 cells were exposed to 0.1 μM calcein for 10 minutes, thoroughly washed, and 1 × 105 cells plated into each well of multiple 96-well plates. After equilibration of the plates at 37° C, aliquots of the individual components of an in-house chemical library of ∼12,000 compounds dissolved in DMSO were screened in duplicate or triplicate and fluorescence measurements made at 0 and 30 min after addition of 10 μM FeNH4SO4 in a Synergy IV plate reader. 30 chemicals were identified that stimulated iron-induced quenching of calcein fluorescence. The stimulation was verified by dose response curves and by assaying the effect on non-transferrin bound 55Fe uptake. None of the stimulators were cytotoxic for up to at least 3 days. The lead compound, LS081, had an IC50 = 1.22 ± 0.48 μM for 55Fe uptake in K562 cells compared to controls. LS081 was also used to examine the iron uptake in Caco2 cells grown in bicameral chambers, a model system to study intestinal iron absorption. LS081 significantly increased 55Fe uptake into Caco2 cells with a very rapid influx of 55Fe in the first 5 min after Fe was offered to the apical surface followed by a ∼ 4-fold increased uptake over the next 90 min. 55Fe transport across the basolateral surface into the basal chamber also increased ∼ 4 fold. The increased 55Fe transport in caco2 cells is more prominent at lower pH of 5.5 compare to pH 7.5 suggesting LS081 acted on a common divalent metal uptake pathway. Mice treated with LS081 + ferric ammonium citrate via oral gavage for two weeks significantly increased (p < 0.001 by unpaired t-test compared to ferric ammonium citrate alone) the level of ferritin, the iron storage protein, in the liver, demonstrating the absorption of LS081 from intestinal cells. In summary, using high through-put screening technique we identified small molecules that stimulate iron uptake and could be used as a drug for iron deficiency. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Comparative Study of Different Oral Iron Preparations in Females of Reproductive Age Group

2021 ◽  
pp. 93-100
Author(s):  
Megha Tiwari ◽  
Vishal Dubey ◽  
Nikita Srivastava
Keyword(s):  
Folic Acid ◽  
Iron Deficiency ◽  
Iron Hydroxide ◽  
Oral Iron ◽  
Reproductive Age ◽  
Ammonium Citrate ◽  
Deficiency Anemia ◽  
Ferric Ammonium Citrate ◽  
Significant Difference ◽  
Ferric Ammonium

Background: Anemia (anemia) is a decrease in the total amount of red blood cells (RBCs) or hemoglobin in the blood, or a lowered ability of the blood to carry oxygen. The commonness of iron inadequacy is high in all age bunch females. Around 32.4% of ladies have mellow iron deficiency, 14.19% ladies have direct sickliness, 2.2% have serious weakness. Objective: The aim of the study is to compare the efficacy and safety profile of oral iron formulations in iron deficiency anemia. Methods: A cross sectional study in patients with anemia receiving oral ferric ammonium citrate, folic acid, vitamin B12and iron hydroxide respectively was included. The patients were followed up once in 0 day, end of week, 1 month, for 3 months and observed for hematological improvement and adverse drug reactions (ADRs). Total 350 anemic patient were included in the study. Results: The data analyzed in 185 patients received ferric ammonium citrate, folic acid, 165 received, iron hydroxide,folic acid, vitamin B12 have significantly improved mean hemoglobin and anemia indices at the end of study, however, there was no significant differences between the groups when compared. “All four formulations showed similar ADR profile, there was no significant difference in adverse reactions.’’ Conclusion: Ferric ammonium citrate can be considered as best cost-effective choice for treatment of irons deficiency anemia.

scholarly journals Ferritin upregulates hepatic expression of bone morphogenetic protein 6 and hepcidin in mice

2012 ◽  
Vol 302 (12) ◽  
pp. G1397-G1404 ◽  
Author(s):  
Qi Feng ◽  
Mary C. Migas ◽  
Abdul Waheed ◽  
Robert S. Britton ◽  
Robert E. Fleming
Keyword(s):  
Bone Morphogenetic Protein ◽  
Iron Status ◽  
Ammonium Citrate ◽  
Ferric Ammonium Citrate ◽  
Hepatic Expression ◽  
Morphogenetic Protein ◽  
Ferric Ammonium ◽  
Liver Ferritin ◽  
Old Mice ◽  
Bone Morphogenetic Protein 6

Hepcidin is a hepatocellular hormone that inhibits the release of iron from certain cell populations, including enterocytes and reticuloendothelial cells. The regulation of hepcidin ( HAMP) gene expression by iron status is mediated in part by the signaling molecule bone morphogenetic protein 6 (BMP6). We took advantage of the low iron status of juvenile mice to characterize the regulation of Bmp6 and Hamp1 expression by iron administered in three forms: 1) ferri-transferrin (Fe-Tf), 2) ferric ammonium citrate (FAC), and 3) liver ferritin. Each of these forms of iron enters cells by distinct mechanisms and chemical forms. Iron was parenterally administered to 10-day-old mice, and hepatic expression of Bmp6 and Hamp1 mRNAs was measured 6 h later. We observed that hepatic Bmp6 expression increased in response to ferritin but was unchanged by Fe-Tf or FAC. Hepatic Hamp1 expression likewise increased in response to ferritin and Fe-Tf but was decreased by FAC. Exogenous ferritin increased Bmp6 and Hamp1 expression in older mice as well. Removing iron from ferritin markedly decreased its effect on Bmp6 expression. Exogenously administered ferritin and the derived iron localized in the liver primarily to sinusoidal lining cells. Moreover, expression of Bmp6 mRNA in isolated adult rodent liver cells was much higher in sinusoidal lining cells than hepatocytes (endothelial >> stellate > Kupffer). We conclude that exogenous iron-containing ferritin upregulates hepatic Bmp6 expression, and we speculate that liver ferritin contributes to regulation of Bmp6 and, thus, Hamp1 genes.

scholarly journals A study on the aspects of pharmacoepidemiology and pharmacohaemovigilance of ferrous ascorbate, ferrous fumarate, ferrous sulphate and ferric ammonium citrate, among the rural anaemic women, in the Indian spectrum

2019 ◽  
Vol 8 (12) ◽  
pp. 2751
Author(s):  
Moumita Hazra
Keyword(s):  
Ferrous Sulphate ◽  
Haemoglobin Concentration ◽  
Significant Rise ◽  
Demographic Characteristics ◽  
Health Concern ◽  
Ammonium Citrate ◽  
Ferric Ammonium Citrate ◽  
Ferrous Fumarate ◽  
Ferrous Ascorbate ◽  
Ferric Ammonium

Background: Anaemia is a global health concern, associated with increased maternal and perinatal mortality, preterm delivery, low birth weight, extreme fatigue and impaired immune system; and controlled by oral haematinics; with a rise in haemoglobin concentration. The objective was to examine the various aspects of pharmacoepidemiology and pharmacohaemovigilance of oral haematinics, among the anaemic women population, in rural India.Methods: This was a multi-centre, retrospective, observational and analytical study of the hospital medical records of 250 anaemic patients, who were allocated into group A of 125 patients within 15-21 years and group B of 125 patients within 22-35 years. The patients were prescribed oral haematinics, containing 60 mg of elemental iron, thrice daily, with meals. The various aspects of pharmacoepidemiology and pharmacohaemovigilance of ferrous ascorbate, ferrous sulphate, ferrous fumarate and ferric ammonium citrate, including patients’ demographic characteristics, anaemic symptoms assessment, prescription patterns, and safety assessment, on 1st, 2nd, 3rd months and follow-up visits, were recorded and thoroughly analysed..Results: In groups A and B, the demographic characteristics of the patients were comparable; ferrous ascorbate was the most commonly prescribed oral haematinic, followed by ferrous sulphate, ferrous fumarate and ferric ammonium citrate, which controlled mild to moderate iron deficiency anaemia, with a gradual significant rise in haemoglobin concentration, in the successive 3 months; and adverse effects were observed to be statistically non-significant in either group.Conclusions: The different aspects of pharmacoepidemiology and pharmacohaemovigilance in the study established that the oral haematinics were reasonably beneficial and safe among the anaemic women population, in rural India.

THE EFFECT OF CERTAIN ORAL AND INJECTABLE IRON PREPARATIONS ON THE BLOOD OF BABY PIGS

1959 ◽  
Vol 39 (2) ◽  
pp. 193-201 ◽  
Author(s):  
H. Doornenbal
Keyword(s):  
Oral Iron ◽  
Ammonium Citrate ◽  
Normal Blood ◽  
Ferric Ammonium Citrate ◽  
Iron Dextran ◽  
Ferric Ammonium ◽  
Iron Sulphate

Haemoglobin levels, haematocrit values and erythrocyte counts were determined at weekly intervals from 3 to 45 days of age for 60 pigs which received iron in the form of: injectable iron-dextran (A); injectable iron-dextran (B); injectable ferric ammonium citrate; oral iron in the form of paste, or sods sprinkled with iron sulphate. The iron-dextran and ferric ammonium citrate compounds were administered at 3 days of age as single injections supplying 100 mgm. of iron and 30 mgm. of ferric ammonium citrate respectively. The paste was administered at 3, 10, 17 and 24 days of age. Sods were fed twice a week during the period of 3 days to 28 days of age.The sod treatment maintained normal blood values while the iron-dextran compounds and the paste resulted in values somewhat below normal, although visible evidence of anaemia was not apparent. Blood values for the group receiving ferric ammonium citrate were extremely low and two pigs on this treatment died at 42 and 60 days of age. Both exhibited severe anaemia.Significant differences were obtained in weaning weights. The heaviest pigs were those receiving sods; the lightest pigs those receiving injectable ferric ammonium citrate. The effect of the different treatments on growth was not apparent until after 21 days of age.

Sign in / Sign up

Export Citation Format

Share Document