Iron overload during the embryonic period develops hyperactive like behavior and dysregulation of biogenic amines in Drosophila melanogaster.

Iron (Fe) is used in various cellular functions, and a constant balance between its uptake, transport, storage, and use is necessary to maintain its homeostasis in the body. Changes in Fe metabolism with a consequent overload of this metal are related to neurological changes and cover a broad spectrum of diseases, mainly when these changes occur during the embryonic period. This work aimed to evaluate the effect of exposure to Fe overload during the embryonic period of Drosophila melanogaster. Progenitor flies (male and female) were exposed to ferrous sulfate (FeSO4) for ten days in concentrations of 0.5, 1, and 5 â€‹mM. After mating and oviposition, the progenitors were removed and the treatment bottles preserved, and the number of daily hatches and cumulative hatching of the first filial generation (F1) were counted. Subsequently, F1 flies (separated by sex) were subjected to behavioral tests such as negative geotaxis test, open field test, grooming, and aggression test. They have evaluated the levels of dopamine (DA), serotonin (5-HT), octopamine (OA), tryptophan and tyrosine hydroxylase (TH), acetylcholinesterase, reactive species, and the levels of Fe in the progenitor flies and F1. The Fe levels of F1 flies are directly proportional to what is incorporated during the period of embryonic development; we also observed a delay in hatching and a reduction in the number of the hatch of F1 flies exposed during the embryonic period to the 5mM Fe diet, a fact that may be related to the reduction of the cell viability of the ovarian tissue of progenitor flies. The flies exposed to Fe (1 and 5 â€‹mM) showed an increase in locomotor activity (hyperactivity) and a significantly higher number of repetitive movements. In addition to a high number of aggressive encounters when compared to control flies. We can also observe an increase in the levels of biogenic amines DA and 5-HT and an increase in TH activity in flies exposed to Fe (1 and 5 â€‹mM) compared to the control group. We conclude that the hyperactive-like behavior demonstrated in both sexes by F1 flies exposed to Fe may be associated with a dysregulation in the levels of DA and 5-HT since Fe is a cofactor of TH, which had its activity increased in this study. Therefore, more attention is needed during the embryonic development period for exposure to Fe overload.

Necesidades de investigación para el diagnóstico de anemia en poblaciones de altura / Diagnosis of anemia in populations at high altitudes

Tanto la deficiencia como la sobrecarga de hierro son situaciones que ponen en riesgo la salud y la vida de las personas, por lo que es importante mantener su homeostasis. Como la hemoglobina contiene 70% del hierro del organismo, la OMS recomienda su medición para determinar la prevalencia de anemia por deficiencia de hierro (ID), a pesar que ellos mismos reconocen que la anemia no es específica de ID. Como la hemoglobina aumenta con la altitud de residencia, la OMS recomienda corregir el punto de corte para definir anemia en la altura. Una objeción a esta corrección es que el aumento de la hemoglobina en la altura no es universal ni aumenta de manera lineal. Además, las poblaciones de mayor antigüedad generacional tienen menos hemoglobina que las más recientes. En infantes, niños, gestantes y adultos, la prevalencia de anemia usando hemoglobina corregida es 3-5 veces mayor que usando marcadores del estatus de hierro. Los programas estatales buscan combatir la anemia mediante la suplementación de hierro; no obstante, resultan ineficaces, especialmente en las poblaciones de altura. Entonces, ¿hay deficiencia de hierro en la altura? Los niveles de hepcidina sérica, hormona que regula la disponibilidad de hierro, son similares a los de nivel del mar indicando que en la altura no hay deficiencia de hierro. Un problema adicional al corregir la hemoglobina por la altura, es que las prevalencias de eritrocitosis disminuyen. En conclusión, la corrección del punto de corte de la hemoglobina en la altura para determinar deficiencia de hierro es inadecuada.

Iron deficiency and overload are risk factors for numerous poor health outcomes, and thus the maintenance of iron homeostasis is vital. Considering that hemoglobin contains 70% of the total iron in the body, the World Health Organization (WHO) recommends the measurement of iron levels to calculate the rate of iron deficiency anemia (IDA), although WHO recognizes that IDA is not the only cause of anemia. As hemoglobin increases with altitude, WHO recommends correcting the cut-off point to define anemia at high altitudes. An objection to this correction is that the increase in hemoglobin at high altitudes is not universal and is not linear. In addition, individuals in older age groups have lower hemoglobin levels than those in younger age groups. In infants, children, pregnant women, and adults, the prevalence of anemia using corrected hemoglobin is 3-5 times higher than that using markers of iron status. State programs seek to control anemia by means of iron supplementation. However, these programs are ineffective, particularly for high-altitude populations. Therefore, the occurrence of iron deficiency at high altitudes is controversial. The serum levels of the hormone hepcidin, which regulates iron availability, are similar in individuals at high altitudes to those of individuals at sea level, indicating that iron deficiency does not occur at high altitudes. An additional problem when correcting hemoglobin at high altitudes is that the frequency of erythrocytosis is decreased. In conclusion, the correction of the cut-off point of hemoglobin at high altitudes to determine iron deficiency is inadequate.

Indoleamine 2,3-dioxygenase and iron are required for Mycobacterium leprae survival.

Our previous study has demonstrated that IL-10 may modulate both indoleamine 2,3-dioxygenase (IDO) and CD163 expression in lepromatous leprosy (LL) cells, favoring Mycobacterium leprae persistence through induction of regulatory pathways and iron storage. Here, we observed that in LL lesion cells there is an increase in the expression of proteins involved in iron metabolism such as hemoglobin (Hb), haptoglobin, heme oxygenase 1 and transferrin receptor 1 (TfR1) when compared to tuberculoid leprosy (BT) cells. We also found increased iron deposits and diminished expression of the iron exporter ferroportin 1 in LL lesion cells. Hemin, but not FeSO4 stimulation, was able to enhance M. leprae viability by a mechanism that involves IDO. Analysis of cell phenotype in lesions demonstrated a predominance of M2 markers in LL when compared with BT lesion cells. A positive correlation between CD163 and PPARG with the bacillary index (BI) was observed. In contrast, TNF, STAT1 and CSF2 presented a negative correlation with the BI. In summary, this study demonstrates that iron may regulate IDO expression by a mechanism that involves IL-10, which may contribute for the predominance of M2-like phenotype in LL lesions that favors the phagocytosis and maintenance of M. leprae in host cells.

Copper(II) and iron(III) ions inhibit respiration and increase free radical-mediated phospholipid peroxidation in rat liver mitochondria: Effect of antioxidants.

Rat liver mitochondria (1.5-2.1mg protein·mL-1) supplemented with either 25 and 100µM Cu2+ or 100 and 500µM Fe3+ show inhibition of active respiration (O2 consumption in state 3) and increased phospholipid peroxidation . Liver mitochondria were supplemented with the antioxidants reduced glutathione, N-acetylcysteine or butylated hydroxitoluene, to evaluate their effects on the above-mentioned alterations. Although the mitochondrial dysfunction is clearly associated to phospholipid peroxidation, the different responses to antioxidant supplementation indicate that the metal ions have differences in their mechanisms of toxicity. Mitochondrial phospholipid peroxidation through the formation of hydroxyl radical by a Fenton/Haber-Weiss mechanism seems to precede the respiratory inhibition and to be the main fact in Fe-induced mitochondrial dysfunction. In the case of Cu2+, it seems that the ion oxidizes glutathione, and low molecular weight protein thiol groups in a direct reaction, as part of its intracellular redox cycling. The processes involving phospholipid peroxidation, protein oxidation and mitochondrial respiratory inhibition characterize a redox dyshomeostatic situation that ultimately leads to cell death. However, Cu2+ exposure involves an additional, yet unidentified, toxic event as previous reduction of the metal with N-acetylcysteine has only a minor effect in preventing the mitochondrial damage.

[Diagnosis of anemia in populations at high altitudes]. / Necesidades de investigación para el diagnóstico de anemia en poblaciones de altura.

Iron deficiency and overload are risk factors for numerous poor health outcomes, and thus the maintenance of iron homeostasis is vital. Considering that hemoglobin contains 70% of the total iron in the body, the World Health Organization (WHO) recommends the measurement of iron levels to calculate the rate of iron deficiency anemia (IDA), although WHO recognizes that IDA is not the only cause of anemia. As hemoglobin increases with altitude, WHO recommends correcting the cut-off point to define anemia at high altitudes. An objection to this correction is that the increase in hemoglobin at high altitudes is not universal and is not linear. In addition, individuals in older age groups have lower hemoglobin levels than those in younger age groups. In infants, children, pregnant women, and adults, the prevalence of anemia using corrected hemoglobin is 3-5 times higher than that using markers of iron status. State programs seek to control anemia by means of iron supplementation. However, these programs are ineffective, particularly for high-altitude populations. Therefore, the occurrence of iron deficiency at high altitudes is controversial. The serum levels of the hormone hepcidin, which regulates iron availability, are similar in individuals at high altitudes to those of individuals at sea level, indicating that iron deficiency does not occur at high altitudes. An additional problem when correcting hemoglobin at high altitudes is that the frequency of erythrocytosis is decreased. In conclusion, the correction of the cut-off point of hemoglobin at high altitudes to determine iron deficiency is inadequate.

Tanto la deficiencia como la sobrecarga de hierro son situaciones que ponen en riesgo la salud y la vida de las personas, por lo que es importante mantener su homeostasis. Como la hemoglobina contiene 70% del hierro del organismo, la OMS recomienda su medición para determinar la prevalencia de anemia por deficiencia de hierro (ID), a pesar que ellos mismos reconocen que la anemia no es específica de ID. Como la hemoglobina aumenta con la altitud de residencia, la OMS recomienda corregir el punto de corte para definir anemia en la altura. Una objeción a esta corrección es que el aumento de la hemoglobina en la altura no es universal ni aumenta de manera lineal. Además, las poblaciones de mayor antigüedad generacional tienen menos hemoglobina que las más recientes. En infantes, niños, gestantes y adultos, la prevalencia de anemia usando hemoglobina corregida es 3-5 veces mayor que usando marcadores del estatus de hierro. Los programas estatales buscan combatir la anemia mediante la suplementación de hierro; no obstante, resultan ineficaces, especialmente en las poblaciones de altura. Entonces, ¿hay deficiencia de hierro en la altura? Los niveles de hepcidina sérica, hormona que regula la disponibilidad de hierro, son similares a los de nivel del mar indicando que en la altura no hay deficiencia de hierro. Un problema adicional al corregir la hemoglobina por la altura, es que las prevalencias de eritrocitosis disminuyen. En conclusión, la corrección del punto de corte de la hemoglobina en la altura para determinar deficiencia de hierro es inadecuada.

Indoleamine 2. 3-dioxygenase and iron are required for Mycobacterium leprae survival

Our previous study has demonstrated that IL-10 may modulate both indoleamine 2,3-dioxygenase (IDO) and CD163 expression in lepromatous leprosy (LL) cells, favoring Mycobacterium leprae persistence through induction of regulatory pathways and iron storage. Here, we observed that in LL lesion cells there is an increase in the expression of proteins involved in iron metabolism such as hemoglobin (Hb), haptoglobin, heme oxygenase 1 and transferrin receptor 1 (TfR1) when compared to tuberculoid leprosy (BT) cells. We also found increased iron deposits and diminished expression of the iron exporter ferroportin 1 in LL lesion cells. Hemin, but not FeSO stimulation, was able to enhance M. leprae viability by a mechanism that involves IDO. Analysis of cell phenotype in lesions demonstrated a predominance of M2 markers in LL when compared with BT lesion cells. A positive correlation between CD163 and PPARG with the bacillary index (BI) was observed. In contrast, TNF, STAT1 and CSF2 presented a negative correlation with the BI. In summary, this study demonstrates that iron may regulate IDO expression by a mechanism that involves IL-10, which may contribute for the predominance of M2-like phenotype in LL lesions that favors the phagocytosis and maintenance of M. leprae in host cells.

Iron from haemoglobin and haemin modulates nucleotide hydrolysis in Trichomonas vaginalis.

Extracellular ATP may act as a danger signalling molecule, inducing inflammation and immune responses in infection sites. The ectonucleotidases NTPDase and ecto-5'-nucleotidase are enzymes that modulate extracellular nucleotide levels; these enzymes have been previously characterised in Trichomonas vaginalis. Iron plays an important role in the complex trichomonal pathogenesis. Herein, the effects of iron on growth, nucleotide hydrolysis and NTPDase gene expression in T. vaginalis isolates from female and male patients were evaluated. Iron from different sources sustained T. vaginalis growth. Importantly, iron from haemoglobin (HB) and haemin (HM) enhanced NTPDase activity in isolates from female patients and conversely reduced the enzyme activity in isolates from male patients. Iron treatments could not alter the NTPDase transcript levels in T. vaginalis. Furthermore, our results reveal a distinct ATP, ADP and AMP hydrolysis profile between isolates from female and male patients influenced by iron from HB and HM. Our data indicate the participation of NTPDase and ecto-5'-nucleotidase in the establishment of trichomonas infection through ATP degradation and adenosine production influenced by iron.

Influência da hipomagnesemia sobre a homeostase do ferro e estresse oxidativo no diabetes mellitus tipo 2 / Influence of hypomagnesemia on iron homeostasis and oxidative stress in type 2 diabetes mellitus

OBJECTIVE: This review aims to bring updated information about the influence of magnesium deficiency on iron homeostasis and oxidative stress in type 2 diabetics. Data source: A bibliographic search was conducted in the databases Bireme, SciELO, Science Direct, PubMed and Portal.periodicos.Capes using the following descriptors: "diabetes mellitus", "magnesium", "iron", "oxidative stress" and "malondialdehyde". Fifty articles related to this literature were selected. Data synthesis: Several studies have shown the influence of hypomagnesemia on oxidative stress in type 2 diabetics. Deficiency of this mineral seems to be related to the induction of hemolysis, which favors the release of iron with overload of this mineral in the body, allowing an increase of the hydroxyl radical through the Fenton reaction and, consequently, oxidative stress. The increase in free iron contributes significantly to the manifestation of lipid peroxidation, which triggers a sequence of lesions in the cell with loss of selectivity in ion exchange and release of the contents of organelles, such as the hydrolytic enzymes of lysosomes, and the formation of cytotoxic products, such as malondialdehyde. CONCLUSIONS: There is scientific evidence that magnesium deficiency alters iron compartmentalization in the body; however, new studies are needed to bring information that would enable the biochemical understanding of the importance of the balance of magnesium and iron concentrations in protecting against the oxidative stress present in type 2 diabetes

OBJETIVO: Esta revisão visa trazer informações atualizadas sobre a influência da deficiência de magnésio na homeostase do ferro e estresse oxidativo em diabéticos tipo 2. Fonte de dados: O levantamento bibliográfico foi realizado nas bases de dados Bireme, Scielo, Science Direct, periódicos Capes e Pubmed com os seguintes descritores: "diabetes mellitus", "magnésio", "ferro", "estresse oxidativo" e "malondialdeído". Foram selecionados 50 artigos entre os relacionados por essa pesquisa bibliográfica. Síntese dos dados: Diversos estudos têm mostrado a influência da hipomagnesemia sobre o estresse oxidativo em diabéticos tipo 2, sendo que a deficiência desse mineral parece estar relacionada à indução da hemólise dos eritrócitos, que favorece a liberação do ferro com sobrecarga desse mineral no organismo, o que possibilita aumento do radical hidroxila por meio da reação de Fenton e, consequentemente, o estresse oxidativo. O aumento de ferro livre contribui de forma relevante para a manifestação da peroxidação lipídica, que desencadeia sequência de lesões na célula, com perda da seletividade na troca iônica e liberação do conteúdo de organelas, como as enzimas hidrolíticas dos lisossomas e a formação de produtos citotóxicos, como o malondialdeído. CONCLUSÕES: Há evidências científicas de que a deficiência de magnésio altera a compartimentalização do ferro no organismo, entretanto a realização de novos estudos é necessária para trazer informações que permitam o entendimento bioquímico da importância do equilíbrio das concentrações de magnésio e ferro na proteção contra o estresse oxidativo presente no diabetes tipo 2

[Micronutrients and diabetes, the case of minerals]. / Micronutrientes y diabetes, el caso de los minerales.

Minerals are essential nutrients for the body, are of inorganic nature which gives them the characteristic of being resistant to heat, are involved in a lot of chemical reactions in metabolism, regulating electrolyte balance, in maintaining bone, in the process of blood clotting and the transmission of nerve impulses, particularly its role as enzyme cofactors confers a key role in various physiological processes. Glucose homeostasis involves a fine coordination of events where hormonal control by insulin plays a key role. However, the role of minerals like magnesium, zinc, chromium, iron and selenium in the diabetes is less obvious and in some cases may be controversial. This review shows the knowledge of these five elements and their correlation with diabetes.

Los minerales son nutrientes esenciales para el organismo, de naturaleza inorgánica que les confiere, entre otras características, ser resistentes al calor, participan en diversas reacciones químicas del metabolismo en donde regulan el equilibrio hidroelectrolítico, el mantenimiento óseo, en la trasmisión de los impulsos nerviosos, y durante el proceso de coagulación sanguínea, particularmente por su función como cofactores enzimáticos, tienen un papel clave en varios procesos fisiológicos. La homeostasis de la glucosa involucra una fina coordinación de eventos en donde el control hormonal por la insulina tiene un papel primordial. Sin embargo, la función de los minerales, como el magnesio, el zinc, el cromo, el hierro y el selenio en la diabetes es menos evidente y puede ser, en algún caso, controversial. Esta revisión muestra el conocimiento acerca de estos cinco elementos y su correlación con la diabetes.

Limbic system pathologies associated with deficiencies and excesses of the trace elements iron, zinc, copper, and selenium.

Deficiencies of nutrients such as amino acids, vitamins, lipids, and trace elements during gestation and early infanthood have strong deleterious effects on the development of the limbic system; these effects may be irreversible, even when adequate supplementation is provided at later developmental stages. Recent advances in the neurochemistry of biometals are increasingly establishing the roles of the trace elements iron, copper, zinc, and selenium in a variety of cell functions and are providing insight into the repercussions of deficiencies and excesses of these elements on the development of the central nervous system, especially the limbic system. The limbic system comprises diverse areas with high metabolic demands and differential storage of iron, copper, zinc, and selenium. This review summarizes available evidence suggesting the involvement of these trace elements in pathological disorders of the limbic system.

Hepcidina: su interacción con la hemojuvelina y su aporte en el diagnóstico de las enfermedades relacionadas con el metabolismo del hierro / Hepcidin: Interaction with Hemojuvelin and its Contribution in the Diagnosis of Diseases Related to Iron Metabolism

La hepcidina es una hormona peptídica, producida en el hígado y considerada unregulador del metabolismo del hierro. Su regulación está dirigida a la absorciónintestinal del hierro y a la función de la ferroportina dentro de la célula, a fin demantener un balance entre el consumo y las reservas de hierro. Esta hormona, a suvez, está regulada por procesos inflamatorios, estados de anemia ferropénica, actividadhematopoyética y algunas vías de señalización como SMAD, STAT y JAK. En estasvías interviene una proteína de membrana llamada hemojuvelina, la cual actúa comoun correceptor de la proteína morfogenética ósea, cuya función es inducir el gende transcripción de la hepcidina mediante la vía SMAD1/5/8-SMAD4. Debido a laasociación de la hemojuvelina con la expresión de la hepcidina y la relación de estaúltima con procesos inflamatorios y regulación del metabolismo del hierro, se hanpropuesto algunas técnicas para la determinación de ambas proteínas como Elisa,Dotblot, inmunoensayos y SELDI-TOF MS...

The hepcidin is a peptide hormone produced by theliver with anti-bacterial activity, is involved in regulationiron metabolism, making it possible to useit as another parameter to assess some entities relatedto disorders associated with iron metabolism.Hepcidin regulates intestinal absorption of ironlevel and the role of ferroportin in the cell, preventingeither iron overload or iron consumptionreserve, this is turn regulating for inflammatorystimuli, iron store, erythropoietic activity andsignaling patway SMAD,STAT and JAK; in thissignaling patway involved a membrane proteincalled hemojuvelin. The hemojuvelin acts as abone morphogenetic protein co-receptor, theyinduce hepcidin gene transcription through theSMAD1/5/8-SMAD4. Because of the associationsof hemojuveline with hepcidin expression andthe relationship of the latter with inflammatoryprocesses and regulations of iron metabolismhave been proposed some techniques for the determinationof both proteins as Elisa, Dotblot,Immunoassays and SELDI-TOF MS...

Iron and holotransferrin induce cAMP-dependent differentiation of Schwann cells.

The differentiation of myelin-forming Schwann cells (SC) is completed with the appearance of myelin proteins MBP and P(0) and a concomitant downregulation of markers GFAP and p75NTR, which are expressed by immature and adult non-myelin-forming SC. We have previously demonstrated that holotransferrin (hTf) can prevent SC dedifferentiation in culture (Salis et al., 2002), while apotransferrin (aTf) cannot. As a consequence, we used pure cultured SC and submitted them to serum deprivation in order to promote dedifferentiation and evaluate the prodifferentiating ability of ferric ammonium citrate (FAC) through the expression of MBP, P(0), p75NTR and c-myc. The levels of cAMP, CREB and p-CREB were also measured. Results show that Fe(3+), either in its free form or as hTf, can prevent the dedifferentiation promoted by serum withdrawal. Both FAC and hTf were proven to promote differentiation, probably through the increase in cAMP levels and CREB phosphorylation, as well as levels of reactive oxygen species. This effect was inhibited by deferroxamine (Dfx, an iron chelator), H9 (a cAMP-PKA antagonist) and N-acetylcysteine (NAC, a powerful antioxidant).

Proteomic profiling of the influence of iron availability on Cryptococcus gattii.

Iron is essential and ubiquitous in living organisms. The competition for this micronutrient between the host and its pathogens has been related to disease establishment. Cryptococcus gattii is an encapsulated yeast that causes cryptococcosis mainly in immunocompetent individuals. In this study, we analyzed the proteomic profile of the C. gattii R265 Vancouver Island isolate under iron-depleted and -repleted conditions by multidimensional protein identification technology (MudPIT) and by 2D-GE. Proteins and key mechanisms affected by alteration of iron levels such as capsule production, cAMP-signaling pathway, response to stress, and metabolic pathways related to mitochondrial function were identified. Our results also show both proteomic methodologies employed to be complementary.

The role of iron in tumour cell proliferation.

Iron has a pivotal role in homeostasis due to its participation in virtually all of the body's oxidation-reduction processes. However, iron can also be considered a double-edged weapon, as its excess may lead to an increased risk of developing cancer, presumably by the generation of reactive oxygen species, and its role as substrate to enzymes that participate in cell proliferation. Thus, iron might as well be considered a cofactor in tumour cell proliferation. In certain pathological conditions, such as haemochromatosis, hepatitis B and C virus infection, asbestosis and endometriosis, iron overload may increase the risk of cancer. By contrast, iron depletion could be considered a useful adjunct in antitumour therapy. This paper reviews the current scientific evidence behind iron's role as a protumoral agent, and the potential benefit of a state of iron depletion in patients with cancer.

Micronutrientes no crescimento e desenvolvimento infantil / Micronutrients in child growth and development

OBJETIVO: abordar a importância dos micronutrientes zinco, ferro e vitamina A no crescimento linear e desenvolvimento infantil. MÉTODO: foram consultadas as bases de dados Medline e LILACS utilizando duas estratégias de busca: i) growth AND zinc AND iron AND vitamin A AND child, preschool OR infant, para o tema micronutrientes e crescimento; e ii) child development AND zinc AND iron AND vitamin A, para o tema micronutrientes e desenvolvimento. Os artigos foram classificados quanto ao tipo de manuscrito e principais resultados. RESULTADOS: foram incluídos 19 artigos referentes ao crescimento e 5 artigos referentes ao desenvolvimento. DISCUSSÃO: considerando as prevalências, sugere-se que as deficiências de ferro e zinco devem contribuir, concurrentemente, com o déficit de estatura. O papel do zinco no sistema hormonal primário justifica ser o nutriente de maior importância no crescimento, afetando a estatura das crianças tanto em estados de deficiência leve como moderada. Evidências fisiológicas e experimentais colocam a importância dos micronutrientes ferro e zinco no desenvolvimento e déficit cognitivo nos primeiros anos da vida. Apesar disso, os resultados ainda não são conclusivos. Pensa-se que o zinco pode limitar processos neuropsicológicos específicos, já o ferro é essencial para o funcionamento do sistema neuro-transmissor. Estudar o efeito das deficiências de micronutrientes no desenvolvimento apresenta vários problemas metodológicos e analíticos. O crescimento e desenvolvimento representam um processo com determinação comum no qual a deficiência de zinco pode representar a forma mais comum em que o crescimento linear poderia ser utilizado como um bom preditor de desenvolvimento cognitivo

Fisiologia e metabolismo do ferro: [revisão] / Iron physiology and metabolism: [review]

O conhecimento sobre a fisiologia e metabolismo do ferro foi bastante incrementado nos últimos anos. A identificação de alguns genes e as repercussões quando de suas mutações, principalmente as relacionadas ao acúmulo de ferro, auxiliaram no entendimento dos mecanismos regulatórios responsáveis pela manutenção da homeostase desse nutriente essencial para numerosos processos bioquímicos. A função de diversas moléculas já está bem estabelecida, como da transferrina e seu receptor e, nas últimas décadas, novas moléculas têm sido identificadas, como a ferroportina, o transportador de metal divalente e hemojuvelina. Um elegante mecanismo de controle mantém o equilíbrio entre os processos de absorção do ferro, reciclagem, mobilização, utilização e estoque. Alterações no sincronismo desses processos podem causar tanto a deficiência como a sobrecarga de ferro, ambos com importantes repercussões clínicas para o paciente. Nessa minirrevisão serão abordados aspectos relacionados ao metabolismo do ferro e à participação de várias proteínas e mediadores envolvidos. Serão também apresentados os mecanismos regulatórios celular e sistêmico responsáveis pela disponibilidade do ferro em concentrações ideais para a manutenção de sua homeostase.

Knowledge of the iron physiology and metabolism has increased greatly over the last few years. The identification of genes and the consequences of mutations, especially those related to the accumulation of iron, have improved the understanding of the regulatory mechanisms responsible for maintaining homeostasis of this essential nutrient in many biochemical processes. The function of several molecules is well established, as in the case of transferrin and its receptor and, in recent decades, new molecules have been identified such as ferroportin, divalent metal transporter, hemojuvelin and hepcidin. An elegant control mechanism maintains the balance between the processes of iron absorption, recycling, mobilization, utilization and storage. Disturbances in the synchronism among those processes may lead either to iron deficiency or to iron overload, both of which have important clinical consequences. This mini-review attempts to describe aspects related to iron metabolism and the participation of several proteins and mediators involved in these mechanisms. Moreover, intracellular and systemic regulation mechanisms responsible for providing the most suitable iron concentration for iron homeostasis maintenance will be presented.

Suplementación con cobre entre comidas no tiene efecto sobre la nutrición de hierro en hombres / Copper supplementation between meals has no effect on iron status of men

Iron deficiency is prevalent in most of the developing world where it coexists with other micronutrient deficiencies such as copper. Combined supplementation with iron and copper is one of the strategies that can be used to improve the iron and copper status of a population. However, there is concern about potential negative interactions between these two micronutrients due to a competitive binding to the divalent metal transporter 1 (DMTl), a proton-coupled transporter of a variety of divalent metals including copper. The aim of this study was to measure the effect of daily supplementation with 8 mg of copper, as copper sulfate during 6 months on the iron status. Sixty healthy male adults were randomized to receive a copper supplement or a placebo. Fasting blood samples were obtained before and after copper supplementation to evaluate the iron and copper nutritional status. Copper supplementation did not change significantly iron and copper status parameters. In conclusion, daily supplementation with 8 mg of copper during 6 months does not deteriorate iron nutrition in adult men.

La deficiencia de hierro coexiste con otras carencias, entre ellas de cobre. La suplementación combinada con estos nutrientes es una de las estrategias utilizadas en su prevención. Sin embargo, existe la posibilidad de interacciones negativas, ya que el DMT1, principal transportador de hierro no hem a nivel intestinal, también transporta cobre. El propósito del estudio fue medir el efecto de la suplementación con 8 mg diarios de cobre, como sulfato de cobre, durante 6 meses, sobre la nutrición de hierro. Sesenta hombres adultos, aparentemente sanos, fueron seleccionados al azar para recibir el suplemento de cobre o un placebo. Se tomaron muestras de sangre en ayunas antes y después de finalizada la suplementacion para evaluar la nutrición de hierro y de cobre. La suplementacion con cobre no determinó cambios significativos en los indicadores de nutrición de cobre y de hierro. En conclusión, la suplementacion con 8 mg diarios de Cu administrado entre comidas durante 6 meses no deterioró la nutrición de hierro en hombres adultos.