Mechanism Of Iron Absorption Research Articles

Nature of storage iron turnover.

Despite recent advance in the study of the nature of storage iron turnover, a comprehensive analysis remains lacking. This study aimed to clarify the nature of storage iron turnover. Ferritin-hemosiderin iron transformation rate and the standard normal storage iron turnover rate were utilized in this study to describe the mechanism of iron absorption in relation to ferritin and hemosiderin iron turnover. The synchronization of radioiron uptake peaks by bone marrow and liver indicates that the distribution of radioiron is proportional to the pre-existing iron levels in organs at 24 h after radioiron injection. Moreover, the synchronization indicates the independence of iron mass from red cell precursors in acquiring plasma iron. Thus, the erythron does not dominate the radioiron uptake process. The inverse correlation between transformation rate and the amount of pre-existing iron storage implies that the intra-storage iron turnover is active in iron deficiency, but inactive in iron overload. The decreased ferritin/hemosiderin iron ratio in chronic hepatitis C (CHC) with normal iron storage suggests a trend of iron transformation from ferritin into hemosiderin. The correlation between the pretreatment iron storage and the speed of rebound in CHC implies that the vacant iron-storing rooms in iron-removed cells have a potential to increase iron absorption. This study presents new insights into the turnover of stored iron to enhance our understanding of iron metabolism in various hematologic disorders.

New insights into the mechanisms of iron absorption: Iron dextran uptake in the intestines of weaned pigs through glucose transporter 5 (GLUT5) and divalent metal transporter 1 (DMT1) transporters

The purpose of this study was to gain insight into the mechanism of iron dextran (DexFe) absorption in the intestines. A total of 72 piglets (average BW=7.12±0.75kg, male to female ratio=1:1) weaned at 28d of age were randomly divided into two treatment groups with six replicates for each group. The experimental diets included the basal diet supplemented with 100mg/kg iron dextran (DexFe group) and the basal diet supplemented with 100mg/kg FeSO4·H2O (CON group). The experiment lasted for 28d. The piglets' intestinal iron transport was measured invitro using an Ussing chamber. Porcine intestinal epithelial cell line (IPEC-J2) cells were used to develop a monolayer cell model that explored the molecular mechanism of DexFe absorption. Results showed that compared to the CON group, the ADG of pigs in the DexFe group was improved (P=0.022), while the F/G was decreased (P=0.015). The serum iron concentration, apparent iron digestibility, and iron deposition in the duodenum, jejunum, and ileum were increased (P<0.05) by dietary DexFe supplementation. Piglets in the DexFe group had higher serum red blood count, hemoglobin, serum iron content, serum ferritin and transferrin levels and lower total iron binding capacity (P<0.05). In the Ussing chamber test, the iron absorption rate of the DexFe group was greater (P<0.001) than the CON group, and there was no significant difference between the DexFe group and the glucose group (P>0.05). Furthermore, when compared to the CON group, DexFe administration improved (P<0.05) SLC2A5 gene and glucose transporter 5 (GLUT5) protein expression but had no effect (P>0.05) on SLC11A2 gene or divalent metal transporter 1 (DMT1) protein expression. Once the GLUT5 protein was suppressed, the iron transport rate and apparent permeability coefficient were decreased (P<0.05) in IPEC-J2 monolayer cell models. The findings suggest the effectiveness of DexFe application in weaned piglets and revealed for the first time that DexFe absorption in the intestine is closely related to the glucose transporter GLUT5 protein channel.

The Iron Metabolism with a Specific Focus on the Functioning of the Nervous System.

Iron is the micronutrient with the best-studied biological functions. It is widely distributed in nature, and its involvement in the main metabolic pathways determines the great importance of this metal for all organisms. Iron is required for cellular respiration and various biochemical processes that ensure the proper functioning of cells and organs in the human body, including the brain. Iron also plays an important role in the production of free radicals, which can be beneficial or harmful to cells under various conditions. Reviews of iron metabolism and its regulation can be found in the literature, and further advances in understanding the molecular basis of iron metabolism are being made every year. The aim of this review is to systematise the available data on the role of iron in the function of the nervous system, especially in the brain. The review summarises recent views on iron metabolism and its regulatory mechanisms in humans, including the essential action of hepcidin. Special attention is given to the mechanisms of iron absorption in the small intestine and the purpose of this small but critically important pool of iron in the brain.

Iron Absorption and its Influencing Factors to Prevent Iron Deficiency

Iron is an important nutrient, required to support tissue oxygen delivery, cell growth and differentiation regulation, and energy metabolism. Body iron levels are mainly controlled by regulation of iron absorption in duodenum and proximal jejunum, allowing absorption to be accurately matched to unregulated losses. Since iron bioavailability often reduced, dietary iron absorption is controlled by cellular and systemic factors to ensure that overall body iron levels are maintained at adequate levels. A better understanding of the mechanism for iron absorption and factors influencing its absorption and bioavailability is important to avoid iron deficiency or iron overload. There are complex regulatory frameworks managing iron absorption, transportation, storage, and recycling. It is able to provide enough iron for critical body functions and react relatively quickly as iron demands increase, but mechanisms must also be in place to restrict iron absorption once the body is overwhelmed with iron. Several factors promote and impede iron absorption, such as phytate and ascorbic acid, respectively. The danger of iron deficiency for the world's population is of great significance, it is important to introduce effective strategies to tackle this issue through nutrition programs; food iron supplements; iron medication supplements; and probiotic, prebiotic, and symbiotic approaches.

Research progress on iron absorption, transport, and molecular regulation strategy in plants.

Iron is a trace element essential for normal plant life activities and is involved in various metabolic pathways such as chlorophyll synthesis, photosynthesis, and respiration. Although iron is highly abundant in the earth's crust, the amount that can be absorbed and utilized by plants is very low. Therefore, plants have developed a series of systems for absorption, transport, and utilization in the course of long-term evolution. This review focuses on the findings of current studies of the Fe2+ absorption mechanism I, Fe3+ chelate absorption mechanism II and plant-microbial interaction iron absorption mechanism, particularly effective measures for artificially regulating plant iron absorption and transportation to promote plant growth and development. According to the available literature, the beneficial effects of using microbial fertilizers as iron fertilizers are promising but further evidence of the interaction mechanism between microorganisms and plants is required.

MxFRO4 confers iron and salt tolerance through up-regulating antioxidant capacity associated with the ROS scavenging

Iron is involved in various metabolic pathways of plants. Stress from iron deficiency and toxicity in the soil adversely affects plant growth. Therefore, studying the mechanism of iron absorption and transport by plants is of important for resistance to iron stress and to increase crop yield. In this study, Malus xiaojinensis (a Fe-efficient Malus plant) was used as research material. A ferric reduction oxidase (FRO) family gene member was cloned and named MxFRO4. The MxFRO4 encoded a protein of 697 amino acid residues with a predicted molecular weight of 78.54kDa and a theoretical isoelectric point of 4.90. A subcellular localization assay showed that the MxFRO4 protein was localized on the cell membrane. The expression of MxFRO4 was enriched in immature leaves and roots of M. xiaojinensis, and was strongly affected by low-iron, high-iron, and salt treatments. After introduction of MxFRO4 into Arabidopsis thaliana, the iron and salt stress tolerance of transgenic A. thaliana was greatly improved. Under exposure to low-iron and high-iron stresses, the primary root length, seedling fresh weight, contents of proline, chlorophyll, and iron, and iron(III) chelation activity of the transgenic lines were significantly increased compared with the wild type. The contents of chlorophyll and proline, and the activities of the antioxidant enzymes superoxide dismutase, peroxidase, and catalase were significantly higher in transgenic A. thaliana overexpressing MxFRO4 under salt stress compared with the wild type, whereas the malondialdehyde content was decreased. These results suggest that MxFRO4 contributes to alleviating the effects of low-iron, high-iron, and salinity stresses in transgenic A. thaliana.

Hemochromatosis-like disease in Brazilian tapirs (Tapirus terrestris) in Pará state, Brazil

ABSTRACT We report two cases of hemochromatosis-like disease in captive Brazilian tapirs, Tapirus terrestris in Pará state, Brazil. Both animals presented symptoms of chronic hepatopathy associated with marked accumulation of hemosiderin. The coloration of Perls demonstrated pronounced iron accumulation in macrophages in the portal space, Kupffer cells, and, to a lesser extent, in the hepatocytes of the periportal region. Marked portal fibrosis was evidenced by Masson’s trichrome. The pathological mechanisms of this disease in tapirs are not yet well established. It has been suggested that the species may have different mechanisms of iron absorption and elimination, rendering them sensitive to elevation in dietary levels of this metal. Two previous reports of this disease in T. terrestris exist from zoos in Australia and Scotland. This is the first report of this disease in tapirs in Brazil based on histopathological and histochemical findings.

Regulation of plant iron homeostasis by abscisic acid: a review

Iron (Fe) is an important trace element involved in many important plant physiological and metabolic processes such as photosynthesis, respiration and nitrogen metabolism. Plants maintain iron homeostasis through absorption, transporting, storage and redistribution of iron. Iron metabolism is strictly regulated in plants. Iron regulatory transcription factors and iron transporters constitute the regulatory network of plant iron absorption and transport in plants. Ferritin and iron transporter jointly regulate the response to excess iron in plants. In recent years, important progress has been made in understanding how abscisic acid (ABA) regulates iron metabolism in plants. ABA may be used as a signal to regulate the absorption, transportation and reuse of Fe, or to relieve the symptoms of iron stress by regulating the oxidative stress responses in plants. In order to gain deeper insights into the crosstalk of ABA and iron metabolism in plants, this review summarized the mechanisms of iron absorption and transport and metabolic regulatory network in plants, as well as the mechanisms of ABA in regulating iron metabolism. The relationship between ABA and FER-like iron deficiency-induced transcription factor (FIT), iron-regulated transporter 1 (IRT1), and oxidative stress of iron deficiency were highlighted, and future research directions were prospected.

Revisiting Iron Metabolism, Iron Homeostasis and Iron Deficiency Anemia.

Iron deficiency anemia (IDA) is one of the commonest clinical scenarios especially in children, women of childbearing age, and elders. The crux of this review was revisiting iron homeostasis, mechanism of iron absorption, causes, laboratory diagnosis, and management of IDA. This narrative review is compiled after a relevant literature search from electronic databases including, but not limited to, Google, Google Scholar, PMC, PubMed, Science Direct, and Scopus. The key words used for searching relevant literature include iron, iron deficiency, iron deficiency anemia, iron metabolism, hepcidin, transferrin, causes of iron deficiency anemia, and laboratory diagnosis of iron deficiency anemia. Reference hema-tology books were also consulted. According to the published literature, about one mg of iron is required daily which equals its loss, although the iron requirement increases in pregnancy and lactating mothers. Dietary non heme iron (oxidized Fe3+) is reduced to the ferrous (Fe2+) form by ferrireductase present in the brush border of duodenal enterocytes. Ferrous iron is absorbed in the brush border of duodenal enterocytes through a carrier protein, divalent metal transporter 1 (DMT1). Heme iron is absorbed by the duodenal enterocytes through a mechanism that is not well understood or a receptor yet to be discovered. Transferrin receptor helps in the internalization of iron in the cells. Hepcidin acts as a gatekeeper and controls iron absorption by enterocytes and macrophages. IDA may be caused by decreased intake of iron, increased iron requirements or loss of iron from the body. Iron deficiency anemia is the most common nutritional anemia that affects large numbers of people in developed as well as in developing countries. It is estimated that approximately 2 billion people around the world have IDA. Microcytosis with marked reduction in serum iron, decreased % saturation of transferrin, low ferritin, and reduced or even undetectable hepcidin are the laboratory features of IDA. In addition, total iron binding capacity and soluble transferrin receptors increase significantly in IDA. Management of IDA is incomplete if the underlying cause is not ruled out and left untreated.

Iron kinetics following treatment with sucroferric oxyhydroxide or ferric citrate in healthy rats and models of anaemia, iron overload or inflammation.

BackgroundThe iron-based phosphate binders, sucroferric oxyhydroxide (SFOH) and ferric citrate (FC), effectively lower serum phosphorus in clinical studies, but gastrointestinal iron absorption from these agents appears to differ. We compared iron uptake and tissue accumulation during treatment with SFOH or FC using experimental rat models.MethodsIron uptake was evaluated during an 8-h period following oral administration of SFOH, FC, ferrous sulphate (oral iron supplement) or control (methylcellulose vehicle) in rat models of anaemia, iron overload and inflammation. A 13-week study evaluated the effects of SFOH and FC on iron accumulation in different organs.ResultsIn the pharmacokinetic experiments, there was a minimal increase in serum iron with SFOH versus control during the 8-h post-treatment period in the iron overload and inflammation rat models, whereas a moderate increase was observed in the anaemia model. Significantly greater increases (P < 0.05) in serum iron were observed with FC versus SFOH in the rat models of anaemia and inflammation. In the 13-week iron accumulation study, total liver iron content was significantly higher in rats receiving FC versus SFOH (P < 0.01), whereas liver iron content did not differ between rats in the SFOH and control groups.ConclusionsIron uptake was higher from FC versus SFOH following a single dose in anaemia, iron overload and inflammation rat models and 13 weeks of treatment in normal rats. These observations likely relate to different physicochemical properties of SFOH and FC and suggest distinct mechanisms of iron absorption from these two phosphate binders.

Determination of Iron Absorption Mechanism From Ferrous Fumarate With GOS

Determination of Iron Absorption Mechanism From Ferrous Fumarate With GOS

Mechanisms, mishaps and manipulation of iron uptake

Mechanisms, mishaps and manipulation of iron uptake

Iron Supplements Containing Lactobacillus plantarum 299v Increase Ferric Iron and Up-regulate the Ferric Reductase DCYTB in Human Caco-2/HT29 MTX Co-Cultures.

Several human interventions have indicated that Lactobacillus plantarum 299v (L. plantarum 299v) increases intestinal iron absorption. The aim of the present study was to investigate possible effects of L. plantarum 299v on the mechanisms of iron absorption on the cellular level. We have previously shown that lactic fermentation of vegetables increased iron absorption in humans. It was revealed that the level of ferric iron [Fe (H2O)5]2+ was increased after fermentation. Therefore, we used voltammetry to measure the oxidation state of iron in simulated gastrointestinal digested oat and mango drinks and capsule meals containing L. plantarum 299v. We also exposed human intestinal co-cultures of enterocytes and goblet cells (Caco-2/HT29 MTX) to the supplements in order to study the effect on proteins possibly involved (MUC5AC, DCYTB, DMT1, and ferritin). We detected an increase in ferric iron in the digested meals and drinks containing L. plantarum 299v. In the intestinal cell model, we observed that the ferric reductase DCYTB increased in the presence of L. plantarum 299v, while the production of mucin (MUC5AC) decreased independently of L. plantarum 299v. In conclusion, the data suggest that the effect of L. plantarum 299v on iron metabolism is mediated through driving the Fe3+/DCYTB axis.

Influence of Physical Activity on the Regulation of Iron Metabolism

Intense physical activity has a significant effect on iron metabolism in the human organism. This paper is a review of world literature data focused on the mechanisms of iron metabolism regulation in the human organism, as well as the influence of intense exercise on these regulatory mechanisms. We have discussed the mechanisms of iron absorption and transport and the regulation of these processes under normal conditions. It has been found that intense exercise is accompanied by increased production of interleukin-6, a positive regulator of hepcidin production. Hepcidin, in turn, has an inhibitory effect on the expression of divalent metal transporter 1 and ferroportin, finally leading to both decreased iron absorption and iron sequestration in cells. All of the mentioned stages of iron deficiency development may be promising targets for correction of iron balance and working ability in patients exposed to intense physical activity.

The management of anaemia and haematinic deficiencies in pregnancy and post-partum.

Anaemia is one of the most common disorders in the world (24·8% of the world population) (de Benoist 2008) and affects patients of all ages and ethnic origins. Underlying causes and prevalences vary by age group and socioeconomic background, but pregnant women everywhere are at high risk of anaemia, the vast majority of cases being due to iron deficiency. One in four pregnant women in Europe are thought to have iron deficiency anaemia (Daru et al., March 2016), whereas in parts of Africa, where hookworm infestation is common, this has been estimated to be as high as 38% (Stevens et al., 2013) to 50% (Bah et al., June 2017). Women of menstruating age are rarely iron replete (Low et al., 18 April 2016) and then enter pregnancy, which carries a major negative iron balance (Bentley, October 1985). Despite a good understanding of the causes of anaemia in pregnancy, there is still uncertainty about how best this should be investigated, prevented and managed. This reflects the limitations of laboratory tests, as well as the poor understanding of how best to replace iron, given the complex physiological mechanisms of iron absorption and distribution. A strategy for iron replacement in a population of anaemic pregnant women needs to be developed not only based on what is biologically and clinically most appropriate but also in the context of each organisation's delivery of care structure, taking into consideration aspects of cost effectiveness. For this reason, management algorithms must be adapted locally, ensuring they meet basic clinical imperatives.

The ferroportin-ceruloplasmin system and the mammalian iron homeostasis machine: regulatory pathways and the role of lactoferrin.

In the last 20years, several new genes and proteins involved in iron metabolism in eukaryotes, particularly related to pathological states both in animal models and in humans have been identified, and we are now starting to unveil at the molecular level the mechanisms of iron absorption, the regulation of iron transport and the homeostatic balancing processes. In this review, we will briefly outline the general scheme of iron metabolism in humans and then focus our attention on the cellular iron export system formed by the permease ferroportin and the ferroxidase ceruloplasmin. We will finally summarize data on the role of the iron binding protein lactoferrin on the regulation of the ferroportin/ceruloplasmin couple and of other proteins involved in iron homeostasis in inflamed human macrophages.

Molecular and cellular bases of iron metabolism in humans

Iron is a microelement with the most completely studied biological functions. Its wide dissemination in nature and involvement in key metabolic pathways determine the great importance of this metal for uni- and multicellular organisms. The biological role of iron is characterized by its indispensability in cell respiration and various biochemical processes providing normal functioning of cells and organs of the human body. Iron also plays an important role in the generation of free radicals, which under different conditions can be useful or damaging to biomolecules and cells. In the literature, there are many reviews devoted to iron metabolism and its regulation in pro- and eukaryotes. Significant progress has been achieved recently in understanding molecular bases of iron metabolism. The purpose of this review is to systematize available data on mechanisms of iron assimilation, distribution, and elimination from the human body, as well as on its biological importance and on the major iron-containing proteins. The review summarizes recent ideas about iron metabolism. Special attention is paid to mechanisms of iron absorption in the small intestine and to interrelationships of cellular and extracellular pools of this metal in the human body.

The importance of iron in pathophysiologic conditions.

Biological iron is necessary for vital functions and also potentially toxic to the organisms. This dual effect raised the interest of many investigators to study the mechanisms controlling its homeostasis that are altered in many pathologic conditions. Recently the understanding of iron metabolism significantly improved with the discovery of genes responsible for genetic disorders, such as hemochromatosis, the IRE/IRPs machinery and the hepcidinferroportin axis, which allowed to elucidate the basis of cellular and systemic iron homeostasis. In addition, these advances disclosed a causal link between deregulation of iron homeostasis, inflammation and oxidative stress, often induced by the iron accumulation that is commonly observed in many pathologic conditions. Hence, believing this was time to provide a current state-ofthe-art on the importance of iron in pathophysiologic conditions, we thought to promote a Research Topic with the contribution of top-leading scientists who studied the effects of iron homeostasis disruption on the outcome of genetic, inflammatory, infectious, cardiovascular, and neurodegenerative diseases. Encountering an interest even larger than our ambitions, we successfully collected 42 manuscripts, which cover the major aspects of iron metabolism, from the essential role of iron for cell survival to its contribution in the pathogenesis of various disorders. They have been organized in an e-book in 7 sections. The first section of the Research Topic includes 11 papers that cover the importance of iron in cellular proliferation, differentiation and functioning, and its crucial role in essential processes such as oxygen transport, DNA synthesis, metabolic energy and cellular respiration. They describe the expression and regulation of the main players involved in the mechanisms of iron absorption, recycling, and mobilization (Zhang et al., 2014), the cooperation among different cellular compartments that facilitates iron mobilization/storage and prevents the deleterious effects induced by its accumulation, the role of iron in the Fenton chemistry and its effects on oxidative stress and programmed cell death. Of interest is the study of the different types of circulating iron and the strategies more commonly used for its detection (Cabantchik, 2014). The papers also present updates on iron metabolism in zebrafish, in C. elegans, the role of iron in the skin and the regulatory mechanisms devoted to iron uptake, recycling and mobilization. Altogether they provide the information for a better understanding of the iron involvement in pathophysiologic conditions. The second section includes three papers dealing with the role of heme inside cells and its cytotoxicity when it is released from hemoproteins. In fact, most body iron is contained within the protoporphyrin ring that acts as prosthetic group in many hemoproteins essential to cellular functions. The different aspects related to heme synthesis, intracellular trafficking, scavenging and catabolism are reviewed together with the protective mechanisms that cooperate to prevent the deleterious effects induced by heme accumulation and the pathological conditions in which heme plays a dominant role (Chiabrando et al., 2014). The expressionand regulation ofthemainhemescavengers and transporters identified are also reviewed, together with the notion that maintenance of heme homeostasis is essential to prevent the deleterious effect induced by its overload (Korolnek and Hamza, 2014). The following sections are devoted to describe how disruption of iron homeostasis is associated with a series of syndromes and dictates the outcomes and severity of these disorders.

Transcriptomic analysis demonstrates the early responses of local ethylene and redox signaling to low iron stress in Malus xiaojinensis

Malus xiaojinensis is an iron-efficient apple species, while the mechanism of its iron tolerance was not fully understood. This study was designed to obtain transcript sequence data and to examine gene expression in roots and leaves under iron deficiency based on RNA-Seq and bioinformatic analysis to provide a foundation for understanding the molecular mechanism of iron absorption after iron starvation. There were 74,839 transcripts with a mean length of 864 bp obtained from 454 and Illumina sequencing. The 21,037 transcripts were expressed differentially in root and leaf samples after iron starvation, involved in iron uptake, iron remobilization, and signal transduction based on GO biological process classification. Iron uptake was enhanced 12 h after iron deficiency treatment, while iron remobilization was reinforced after 2 days iron deficiency. Ethylene and reactive oxygen scavenger (ROS)-mediated signaling pathways were activated after 12 h of iron starvation, while the auxin-signaling pathway was inhibited at 12 h and activated on the 2nd day of iron starvation. Abscisic acid (ABA) and jasmonic acid (JA) signal pathway responded after 2 days of iron starvation. Therefore, in M. xiaojinensis, iron uptake was enhanced in the earlier period and iron remobilization was promoted in the later period of iron deficiency. Ethylene and ROS signaling pathway responded in the earlier period.

Iron deficiency increases blood concentrations of neurotoxic metals in children.

Iron deficiency affects approximately one-third of the world's population, occurring most frequently in children aged 6 months to 3 years. Mechanisms of iron absorption are similar to those of other divalent metals, particularly manganese, lead, and cadmium, and a diet deficient in iron can lead to excess absorption of manganese, lead, and cadmium. Iron deficiency may lead to cognitive impairments resulting from the deficiency itself or from increased metal concentrations caused by the deficiency. Iron deficiency combined with increased manganese or lead concentrations may further affect neurodevelopment. We recently showed that blood manganese and lead concentrations are elevated among iron-deficient infants. Increased blood manganese and lead levels are likely associated with prolonged breast-feeding, which is also a risk factor for iron deficiency. Thus, babies who are breast-fed for prolonged periods should be given plain, iron-fortified cereals or other good sources of dietary iron.