Search

In pigs, iron deficiency anemia (IDA) is a common disorder that occurs during the early postnatal period, leading to the stunted growth and increased mortality of piglets. The main cause of IDA is low iron stores in the liver of newborn piglets; these stores constitute the main source of iron needed to satisfy the erythropoietic requirements of the piglets in their first weeks of life. Insufficient iron stores in piglets are usually due to the inadequate placental iron transfer from the sow to the fetuses. Therefore, iron supplementation in pregnant sows has been implemented to enhance placental iron transfer and increase iron accumulation in the liver of the fetuses. Over the years, several oral and parenteral approaches have been attempted to supplement sows with various iron preparations, and consequently, to improve piglets' red blood cell indices. However, there is debate with regard to the effectiveness of iron supplementation in pregnant sows for preventing IDA in newborn piglets. Importantly, this procedure should be carried out with caution to avoid iron over-supplementation, which can lead to iron toxicity. This article aims to critically review and evaluate the use of iron supplementation in pregnant sows as a procedure for preventing IDA in piglets. [ABSTRACT FROM AUTHOR]

Kidneys play an especial role in copper redistribution in the organism. The epithelial cells of proximal tubules perform the functions of both copper uptake from the primary urine and release to the blood. These cells are equipped on their apical and basal membrane with copper transporters CTR1 and ATP7A. Mosaic mutant mice displaying a functional dysfunction of ATP7A are an established model of Menkes disease. These mice exhibit systemic copper deficiency despite renal copper overload, enhanced by copper therapy, which is indispensable for their life span extension. The aim of this study was to analyze the expression of Slc31a1 and Slc31a2 genes (encoding CTR1/CTR2 proteins) and the cellular localization of the CTR1 protein in suckling, young and adult mosaic mutants. Our results indicate that in the kidney of both intact and copper-injected 14-day-old mutants showing high renal copper content, CTR1 mRNA level is not up-regulated compared to wild-type mice given a copper injection. The expression of the Slc31a1 gene in 45-day-old mice is even reduced compared with intact wild-type animals. In suckling and young copper-injected mutants, the CTR1 protein is relocalized from the apical membrane to the cytoplasm of epithelial cells of proximal tubules, the process which prevents copper transport from the primary urine and, thus, protects cells against copper toxicity. [ABSTRACT FROM AUTHOR]

Iron is an essential micronutrient for almost all living organisms. It plays an important role in DNA, RNA, and protein synthesis and takes part in electron transport, cellular respiration, cell proliferation and differentiation, and gene expression regulation. However, there is a fine line between excessive and insufficient body iron content. Iron overload is biochemically dangerous. It causes serious toxicities and generates reactive oxygen species via the Fenton reaction, leading to damage to cellular membranes, proteins, and DNA. Omega-3 fatty acids play an essential role in many physiological processes, including energy metabolism and signal transduction, as well as acting as structural components of cell membranes. Omega-3 fatty acids also help to maintain homeostasis and combat diseases. Recent studies using model organisms as well as clinical studies have revealed a link between omega-3 fatty acids and iron metabolism. Moreover, various iron-related disorders are significantly affected by omega-3 fatty acids. There is a clear relationship between iron and omega-3 fatty acid metabolisms; however, the underlying mechanisms are unknown. Therefore, in-depth research is needed to determine the exact nature of the metabolic interactions of these nutrients. Here, we focus on iron and omega-3 fatty acid metabolisms at their crossroads in the liver and brain. [ABSTRACT FROM AUTHOR]

Heme is an efficient source of iron in the diet, and heme preparations are used to prevent and cure iron deficiency anemia in humans and animals. However, the molecular mechanisms responsible for heme absorption remain only partially characterized. Here, we employed young iron-deficient piglets as a convenient animal model to determine the efficacy of oral heme iron supplementation and investigate the pathways of heme iron absorption. The use of bovine hemoglobin as a dietary source of heme iron was found to efficiently counteract the development of iron deficiency anemia in piglets, although it did not fully rebalance their iron status. Our results revealed a concerted increase in the expression of genes responsible for apical and basolateral heme transport in the duodenum of piglets fed a heme-enriched diet. In these animals the catalytic activity of heme oxygenase 1 contributed to the release of elemental iron from the protoporphyrin ring of heme within enterocytes, which may then be transported by the strongly expressed ferroportin across the basolateral membrane to the circulation. We hypothesize that the well-recognized high bioavailability of heme iron may depend on a split pathway mediating the transport of heme-derived elemental iron and intact heme from the interior of duodenal enterocytes to the bloodstream. [ABSTRACT FROM AUTHOR]

Highlights: [•] The [EMPIP][EtSO4], [EMMOR][EtSO4], [EMPYR][EtSO4] and its aqueous mixtures have been studied. [•] The density, dynamic viscosity and SLE have been determined. [•] The excess molar volumes and viscosity deviations have been calculated. [•] The NRTL, Wilson, UNIQUAC, Redlich–Kister and VFT equations have been used to correlate the experimental data. [ABSTRACT FROM AUTHOR]

Heme, a ferrous iron protoporphyrin IX complex, is employed as a prosthetic group in a number of diverse heme proteins that participate in important cellular and systemic physiological processes. Provision of an adequate amount of iron for heme biosynthesis is one of the elemental hallmarks of intracellular iron homeostasis. In the cell the bioavailability of iron for the two main iron biological pathways - heme synthesis and the biogenesis of iron-sulfur clusters ([Fe-S]) - is mainly regulated by the IRP/IRE posttranscriptional system. The biogenesis of [Fe-S] centers is crucial for heme synthesis because these co-factors determine the activity of IRP1 and that of ferrochelatase, an enzyme responsible for the insertion of an iron into protoporphyrin IX to produce heme. On the other hand, delivery of iron for heme and hemoglobin synthesis in erythroblasts, precursors of erythrocytes in bone marrow, is an indispensable element of body iron homeostasis. This process relies on the recovery of iron from senescent red blood cells through the enzymatic degradation of heme molecules and recycling of iron to the circulation. Molecular coordination of these processes involves the activity of heme oxygenase 1, IRP1 and IRP2 as well as the functioning of the hepcidin-ferroportin regulatory axis. Recent studies show in mammals the existence of an expanded system of proteins involved in the transport of intact heme molecules at the cellular and systemic levels. The biological role of this system is of particular importance when the concentration of free heme reaches a toxic level in the body (intravascular hemolysis) as well as locally in cells having intensive heme metabolism such as erythroblasts and macrophages. [ABSTRACT FROM AUTHOR]

Molecular iron metabolism and its regulation are least well understood in the fetal and early postnatal periods of mammalian ontogenic development. The scope of this review is to summarize recent progress in uncovering the molecular mechanisms of fetal iron homeostasis, introduce the molecules involved in iron transfer across the placenta, and briefly explain the role of iron transporters in the absorption of this microelement during early postnatal life. These issues are discussed and parallels are drawn with the relatively well-established system for elemental and heme iron regulation in adult mammals. We conclude that detailed investigations into the regulatory mechanisms of iron metabolism at early stages of development are required in order to optimize strategies to prevent neonatal iron deficiency. We propose that newborn piglets represent a suitable animal model for studies on iron deficiency anemia in neonates. [ABSTRACT FROM AUTHOR]

Preterm infants are most at risk of iron deficiency. However, our knowledge of the regulation of iron homeostasis in preterm infants is poor. The main goal of our research was to develop and validate an animal model of human prematurity to assess iron status in preterm infants. We performed a cesarean section on sows on the 109th day of pregnancy, which corresponds to the last trimester of human pregnancy. Preterm piglets showed decreased body weight, red blood cell indices, plasma iron level and transferrin saturation. Interestingly, higher hepatic and splenic non-heme iron content and plasma and hepatic ferritin levels were found in premature piglets compared with term ones. In addition, premature piglets showed higher mRNA levels of iron-regulatory hormone hepcidin in the liver than term animals, which have not been reflected in higher plasma hepcidin-25 levels. We also showed changes in hepcidin regulators, including hepatic bone morphogenetic protein 6, plasma erythroferrone and growth differentiation factor 15 in preterm piglets. Consequently, no difference was observed in iron-exporter ferroportin levels in the spleen and liver. Overall, it seems that premature piglets show a pattern of iron metabolism characteristic of functional iron deficiency and iron accumulation in the tissue. [ABSTRACT FROM AUTHOR]

Iron deficiency is the most common mammalian nutritional disorder. However, among mammalian species iron deficiency anemia (IDA), occurs regularly only in pigs. To cure IDA, piglets are routinely injected with high amounts of iron dextran (FeDex), which can lead to perturbations in iron homeostasis. Here, we evaluate the therapeutic efficacy of non-invasive supplementation with Sucrosomial iron (SI), a highly bioavailable iron supplement preventing IDA in humans and mice and various iron oxide nanoparticles (IONPs). Analysis of red blood cell indices and plasma iron parameters shows that not all iron preparations used in the study efficiently counteracted IDA comparable to FeDex-based supplementation. We found no signs of iron toxicity of any tested iron compounds, as evaluated based on the measurement of several toxicological markers that could indicate the occurrence of oxidative stress or inflammation. Neither SI nor IONPs increased hepcidin expression with alterations in ferroportin (FPN) protein level. Finally, the analysis of the piglet gut microbiota indicates the individual pattern of bacterial diversity across taxonomic levels, independent of the type of supplementation. In light of our results, SI but not IONPs used in the experiment emerges as a promising nutritional iron supplement, with a high potential to correct IDA in piglets. [ABSTRACT FROM AUTHOR]

A single dose of bovine lactoferrin (BLF) was given intravenously (i.v.) to CFW mice 24 hours (h) prior to the i.v. injection of the E. coli lethal dose (LD100). BLF strongly accelerated the clearance rate of E. coli from the blood as well as its killing rate in the liver, lungs, spleen and kidney. The highest clearing and killing rate was found 5 h after E. coli LD100 injection. The most intensive killing in the organs examined was found in the lungs and kidney. Analysis of organs of i.v. BLF-stimulated mice which survived up to day 30 after the infection by E. coli showed that not all animals were definitely pathogen-free. It was concluded that the defense system generated by BLF in mice in vivo is primarily a bacteria-killing one. The participation and cooperation of reticulo-endothelial (RE)-macrophages and granulocytes in the phagocytosis and killing of E. coli may thus be related to the protective activity of LF. [ABSTRACT FROM AUTHOR]

Owing to its redox properties, copper is a cofactor of enzymes that catalyze reactions in fundamental metabolic processes. However, copper–oxygen interaction, which is a source of toxic oxygen radicals generated by the Fenton reaction, makes copper a doubled-edged-sword in an oxygen environment. Among the microelements influencing male fertility, copper plays a special role because both copper deficiency and overload in the gonads worsen spermatozoa quality and disturb reproductive function in mammals. Male gametes are produced during spermatogenesis, a multi-step process that consumes large amounts of oxygen. Germ cells containing a high amount of unsaturated fatty acids in their membranes are particularly vulnerable to excess copper-mediated oxidative stress. In addition, an appropriate copper level is necessary to initiate meiosis in premeiotic germ cells. The balance between essential and toxic copper concentrations in germ cells at different stages of spermatogenesis and in Sertoli cells that support their development is handled by a network of copper importers, chaperones, recipient proteins, and exporters. Here, we describe coordinated regulation/functioning of copper-binding proteins expressed in germ and Sertoli cells with special emphasis on copper transporters, copper transporting ATPases, and SOD1, a copper-dependent antioxidant enzyme. These and other proteins assure copper bioavailability in germ cells and protection against copper toxicity. [ABSTRACT FROM AUTHOR]

In most mammals, neonatal intravascular hemolysis is a benign and moderate disorder that usually does not lead to anemia. During the neonatal period, kidneys play a key role in detoxification and recirculation of iron species released from red blood cells (RBC) and filtered out by glomeruli to the primary urine. Activity of heme oxygenase 1 (HO1), a heme-degrading enzyme localized in epithelial cells of proximal tubules, seems to be of critical importance for both processes. We show that, in HO1 knockout mouse newborns, hemolysis was prolonged despite a transient state and exacerbated, which led to temporal deterioration of RBC status. In neonates lacking HO1, functioning of renal molecular machinery responsible for iron reabsorption from the primary urine (megalin/cubilin complex) and its transfer to the blood (ferroportin) was either shifted in time or impaired, respectively. Those abnormalities resulted in iron loss from the body (excreted in urine) and in iron retention in the renal epithelium. We postulate that, as a consequence of these abnormalities, a tight systemic iron balance of HO1 knockout neonates may be temporarily affected. [ABSTRACT FROM AUTHOR]

Neonatal iron deficiency anemia is prevalent among domestic pigs but does not occur in the offspring of wild boar. The main causes of this disorder in piglets of modern pig breeds are paucity of hepatic iron stores, high birth weight, and rapid growth. Replenishment of fetal iron stores is a direct result of iron transfer efficiency across the placenta. In this study, we attempted to investigate the molecular potential of iron transfer across the placenta as a possible cause of differences between wild boar and Polish Large White (PLW) offspring. Furthermore, by analyzing placentas from PLW gilts that had litters of different sizes, we aimed to elucidate the impact of the number of fetuses on placental ability to transport iron. Using RNA sequencing, we examined the expression of iron-related genes in the placentas from wild boar and PLW gilts. We did not reveal significant differences in the expression of major iron transporters among all analyzed placentas. However, in wild boar placentas, we found higher expression of copper-dependent ferroxidases such as ceruloplasmin, zyklopen, and hephaestin, which facilitate iron export to the fetal circulation. We also determined a close co-localization of ceruloplasmin and zyklopen with ferroportin, the only iron exporter. [ABSTRACT FROM AUTHOR]

Moderate intravascular hemolysis is a common condition in newborns. It is followed by the accumulation of bilirubin, which is a secondary product of the activity of heme oxygenase-1, an enzyme that catalyzes the breakdown of heme released from disrupted erythrocytes and taken up by hepatic macrophages. Although these cells are a major site of enzymatic heme breakdown in adults, we show here that epithelial cells of proximal tubules in the kidneys perform the functions of both heme uptake and catabolism in mouse neonates. A time-course study examining mouse pups during the neonatal period showed a gradual recovery from hemolysis, and concomitant decreases in the expression of heme-related genes and non-heme iron transporters in the proximal tubules. By adjusting the expression of iron-handling proteins in response to the disappearance of hemolysis in mouse neonates, the kidneys may play a role in the detoxification of iron and contribute to its recirculation from the primary urine to the blood. [ABSTRACT FROM AUTHOR]

Iron deficiency is the most common mammalian nutritional deficiency during the neonatal period. However, among mammalian species neonatal iron deficiency anemia (IDA), the most severe consequence of iron scarcity, occurs regularly in pigs. Although intramuscular supplementation of piglets with high amounts of iron dextran (FeDex) is largely considered an appropriate preventive therapy for IDA prophylaxis, an increasing evidence shows that it negatively affects pig physiology. The aim of our study was to evaluate the efficacy of non-invasive supplementation of piglets with sucrosomial ferric pyrophosphate (SFP), a highly bioavailable dietary iron supplement in preventing IDA, in humans and mice. Results of our study show that SFP given to piglets per os in the amount of 6 mg Fe daily efficiently counteracts IDA at a rate comparable with the traditional FeDex-based supplementation (100 mgFe/kG b.w.; i.m. injection). This was indicated by physiological values of red blood cell indices and plasma iron parameters measured in 28-day old piglets. Moreover, SFP-supplemented piglets showed significantly lower (P ≤0.05) plasma level of 8-isoprostane, a biomarker for oxidative stress compared to FeDex-treated animals, implying lesser toxicity of this order of iron replenishment. Finally, supplementation with SFP does not increase considerably the blood plasma hepcidin, a peptide that acts to inhibit iron absorption from the diet. SFP emerges as a promising nutritional iron supplement, with a high potential to be adopted in the postnatal period. [ABSTRACT FROM AUTHOR]

Background: The critically low hepatic iron stores of newborn piglets are considered to be a major cause of neonatal iron deficiency in modern breeds of domestic pig (Sus domestica). The main factor believed to contribute to this phenomenon is large litter size, which has been an objective of selective breeding of pigs for decades. As consequence, iron transferred from the pregnant sow has to be distributed among a greater number of fetuses. Results: Here, we investigated whether litter size influences red blood cell (RBC) indices and iron parameters in Polish Large White (PLW) piglets and gilts. Small and large litters were produced by the transfer of different numbers of embryos, derived from the same superovulated donor females, to recipient gilts. Piglets from large litters obtained following routine artificial insemination were also examined. Our results clearly demonstrated that varying the number of piglets in a litter did not affect the RBC and iron status of 1-day-old piglets, with all showing iron deficiency anemia. In contrast, gilts with small litters displayed higher RBC and iron parameters compared to mothers with large litters. A comparative analysis of the RBC status of wild boars (having less than half as many piglets per litter as domestic pigs) and PLW pigs, demonstrated higher RBC count, hemoglobin level and hematocrit value of both wild boar sows and piglets, even compared to small-litter PLW animals. Conclusions: These findings provide evidence that RBC and iron status in newborn PLW piglets are not primarily determined by litter size, and indicate the need to study the efficiency of iron transport across the placenta in domestic pig and wild boar females. [ABSTRACT FROM AUTHOR]

Iron-deficiency anaemia in piglets causes significant losses in animal production. Although this pathology has already been extensively investigated for several decades, we are still looking for best prevention methods. Currently, molecular techniques are being used to study iron absorption in the body. Biochemical and haematological tests, however, continue to be the basis for diagnosis. The latest generation of haematology analysers make it possible to predict the function of the red cell system on the basis of reticulocyte parameters. Mean reticulocyte haemoglobin content deserves special attention. This parameter is commonly used in human medicine, and may also be applicable in veterinary studies, especially in diagnosing iron deficiency anaemia in piglets. [ABSTRACT FROM AUTHOR]

Among livestock, domestic pig (Sus scrofa) is a species, in which iron metabolism has been most intensively examined during last decade. The obvious reason for studying the regulation of iron homeostasis especially in young pigs is neonatal iron deficiency anemia commonly occurring in these animals. Moreover, supplementation of essentially all commercially reared piglets with iron entails a need for monitoring the efficacy of this routine practice followed in the swine industry for several decades. Since the discovery of hepcidin many studies confirmed its role as key regulator of iron metabolism and pointed out the assessment of its concentrations in biological fluids as diagnostic tool for iron-related disorder. Here we demonstrate that urine hepcidin-25 levels measured by a combination of weak cation exchange chromatography and time-of-flight mass spectrometry (WCX-TOF MS) are highly correlated with mRNA hepcidin expression in the liver and plasma hepcidin-25 concentrations in anemic and iron-supplemented 28-day old piglets. We also found a high correlation between urine hepcidin level and hepatic non-heme iron content. Our results show that similarly to previously described transgenic mouse models of iron disorders, young pigs constitute a convenient animal model to explore accuracy and relationship between indicators for assessing systemic iron status. [ABSTRACT FROM AUTHOR]

Fatigue is a common, non-specific symptom that often impairs patients' quality of life. Even though fatigue may be the first symptom of many serious diseases, it is often underestimated due to its non-specific nature. Iron metabolism disorders are a prominent example of conditions where fatigue is a leading symptom. Whether it is an iron deficiency or overload, tiredness is one of the most common features. Despite significant progress in diagnosing and treating iron pathologies, the approach to chronic fatigue syndrome in such patients is not precisely determined. Our study aims to present the current state of knowledge on fatigue in patients with deteriorated iron metabolism. [ABSTRACT FROM AUTHOR]

• Granite and basalt meals are used as fertilizers due to their mineral composition. • Unfortunately, they are rich in radionuclides which may pose radioactive hazard. • Granite meals have higher content of 40K, 226Ra and 232Th than basalt meals. • Radioactive hazard indices exceed the permissible values in case of granite meals. • The results indicate that the use of basalt meal does not pose a radiological risk. Granite and basalt meals (rock meals) are regarded as micronutrient fertilizers due to their rich content of macro- and microelements essential for proper development of planta. However, they also are rich in radionuclides which may pose a radioactive hazard to environment, food and people. The aim of this study was to assess the environmental and human exposure to ionizing radiation emitted by natural radioactive isotopes containing in granite and basalt meals increasingly used for soil fertilization. Gamma ray spectrometry was applied in order to determine concertation of radioactive isotopes: 40K, 226Ra and 232Th. Afterwards, radiological hazard parameters were calculated in order to assess health and environmental risks. The obtained results indicated that the average radioactivity concentration of 226Ra, 232Th and 40K of all granite meal samples were higher than their average content in the Earth's crust. Whereas, basalt meals contained much lower natural radioactive isotopes. Similarly, the radiological hazard indices were higher and exceeded limit values in case of granite meals, thus excluding them from use in fertilization. Basalt meals were characterized by lower values of these indices, suggesting the possibility of their safe use in agriculture as soil fertilizers. [ABSTRACT FROM AUTHOR]

Simple Summary: In most mammals, including humans, the need for iron increases rapidly in the last period of pregnancy. Therefore, in compliance with World Health Organization (WHO) recommendations, iron supplementation has become a standard procedure even in healthy pregnant women although it carries the risk of iron toxicity and dysregulation of systemic iron homeostasis. Due to physiological and genomic similarities between swine and humans, pigs constitute an useful animal model in nutritional studies during pregnancy. Here, healthy pregnant sows were supplemented with sucrosomial ferric pyrophosphate (SFP), a new non-heme iron formulation, to study its effect on their iron metabolism and that of their progeny. In particular, we aimed at verifying whether supplementation of pregnant sows with SFP will increase the level of low hepatic iron stores in newborn piglets. Results of our study show that SFP does not significantly alter neither systemic iron homeostasis in pregnant sows, nor hepatic iron stores in newborn piglets, which can be used during neonatal period for the maintenance of hematological status. We hypothesize that supplemental iron given orally to pregnant sows is poorly transferred across the placenta. Background: The similarities between swine and humans in physiological and genomic patterns, as well as significant correlation in size and anatomy, make pigs an useful animal model in nutritional studies during pregnancy. In humans and pigs iron needs exponentially increase during the last trimester of pregnancy, mainly due to increased red blood cell mass. Insufficient iron supply during gestation may be responsible for the occurrence of maternal iron deficiency anemia and decreased iron status in neonates. On the other hand, preventive iron supplementation of non-anemic mothers may be of potential risk due to iron toxicity. Several different regimens of iron supplementation have been applied during pregnancy. The majority of oral iron supplementations routinely applied to pregnant sows provide inorganic, non-heme iron compounds, which exhibit low bioavailability and intestinal side effects. The aim of this study was to check, using pig as an animal model, the effect of sucrosomial ferric pyrophosphate (SFP), a new non-heme iron formulation on maternal and neonate iron and hematological status, placental transport and pregnancy outcome; Methods: Fifteen non-anemic pregnant sows were recruited to the experiment at day 80 of pregnancy and randomized into the non-supplemented group (control; n = 5) and two groups receiving oral iron supplementation—sows given sucrosomial ferric pyrophosphate, 60 mg Fe/day (SFP; n = 5) (SiderAL®, Pisa, Italy) and sows given ferrous sulfate 60 mg Fe/day (Gambit, Kutno, Poland) (FeSO4; n = 5) up to delivery (around day 117). Biological samples were collected from maternal and piglet blood, placenta and piglet tissues. In addition, data on pregnancy outcome were recorded.; Results: Results of our study show that both iron supplements do not alter neither systemic iron homeostasis in pregnant sows nor their hematological status at the end of pregnancy. Moreover, we did not detect any changes of iron content in the milk and colostrum of iron supplemented sows in comparison to controls. Neonatal iron status of piglets from iron supplemented sows was not improved compared with the progeny of control females. No statistically significant differences were found in average piglets weight and number of piglets per litter between animals from experimental groups. The placental expression of iron transporters varied depending on the iron supplement. [ABSTRACT FROM AUTHOR]

Mosaic mutant mice displaying functional dysfunction of Atp7a copper transporter (the Menkes ATPase) are an established animal model of Menkes disease and constitute a convenient tool for investigating connections between copper and iron metabolisms. This model allows to explore changes in iron metabolism in suckling mutant mice suffering from systemic copper deficiency as well as in young and adult ones undergone copper therapy, which reduces lethal effect of the Atp7a gene mutation. Our recent study demonstrated that 14-day-old mosaic mutant males display blood cell abnormalities associated with intravascular hemolysis, and show disturbances in the functioning of the hepcidin-ferroportin regulatory axis, which controls systemic iron homeostasis. We thus aimed to check whether copper supplementation recovers mutants from hemolytic insult and rebalance systemic iron regulation. Copper supplementation of 14-day-old mosaic mutants resulted in the reestablishment of hematological status, attenuation of hepicidin and concomitant induction of the iron exporter ferroportin/Slc40a1 expression in the liver, down-regulated in untreated mutants. Interestingly, treatment of wild-type males with copper, induced hepcidin-independent up-regulation of ferroportin protein level in hepatic macrophages in both young and adult (6-month-old) animals. Stimulatory effect of copper on ferroportin mRNA and protein levels was confirmed in bone marrow-derived macrophages isolated from both wild-type and mosaic mutant males. Our study indicates that copper is an important player in the regulation of the Slc40a1 gene expression. [ABSTRACT FROM AUTHOR]

Iron regulatory protein 1 (IRP1) is a cytosolic bifunctional [4Fe-4S] protein which exhibits aconitase activity or binds iron responsive elements (IREs) in untranslated regions of specific mRNA encoding proteins involved in cellular iron metabolism. Superoxide radical (O2.-) converts IRP1 from a [4Fe-4S] aconitase to a [3Fe-4S] „null” form possessing neither aconitase nor trans-regulatory activity. Genetic ablation of superoxide dismutase 1 (SOD1), an antioxidant enzyme that acts to reduce O2. - concentration, revealed a new O2. --dependent regulation of IRP1 leading to the reduction of IRP1 protein level and in consequence to the diminution of IRP1 enzymatic and IRE-binding activities. Here, we attempted to establish whether developmental changes in SOD1 activity occurring in the mouse liver, impact IRP1 expression. We show no correlation between hepatic SOD1 activity and IRP1 protein level neither in pre- nor postnatal period probably because the magnitude of developmental fluctuations in SOD1 activity is relatively small. The comparison of SOD1 activity in regards to IRP1 protein level in the liver of threeSOD1 genotypes (Sod1+/+, Sod1+/- and Sod1-/-) demonstrates that only drastic SOD1 deficiency leads to the reduction of IRP1 protein level. Importantly, we found that in the liver of fetuses lacking SOD1, IRP1 is not down-regulated. To investigate O2. --dependent regulation of IRP1 in a cellular model, we exposed murine RAW 264.7 and bone marrow-derived macrophages to paraquat, widely used as a redox cycler to stimulate O2. -production in cells. We showed that IRP1 protein level as well as aconitase and IRE-binding activities are strongly reduced in macrophages treated with paraquat. The analysis of the expression of IRP1-target genes revealed the increase in L-ferritin protein level resulting from the enhanced transcriptional regulation of the LFt gene and diminished translational repression of L-ferritin mRNA by IRP1. We propose that O2. --dependent up-regulation of this cellular protectant in paraquat-treated macrophages may counterbalance iron-related toxic effects of O2. -. [ABSTRACT FROM AUTHOR]

Iron deficiency anemia is associated with maternal morbidity and poor pregnancy outcomes. Heme and non-heme iron transport proteins expressed in the placenta help in adequate iron supply from anemic mother to fetus. Here we examined the expression of placental iron trafficking molecules and their association with maternal and neonatal iron status in pregnant women with iron deficiency anemia (IDA). Pregnant women who received prenatal care at Christian Medical College, Vellore, India for childbirth were recruited. Pregnant women who were 18–35 years old with gestational age (GA) of ≥36 weeks were eligible to participate in the study. In a prospective cohort of pregnant women, 22 % were iron deficiency anemia and 42 % were iron replete. Samples were collected (Maternal blood, placental tissue, and cord blood) from pregnant women with a gestational age of ≥38 weeks at the time of delivery. The mean gestational age at the first visit and delivery was 12.8 ± 2.72 weeks and 39 ± 1.65 weeks, respectively. Hemoglobin (9.3 ± 0.9 g/dl) and ferritin (15.4(0.8–28.3) ng/ml) levels at delivery were significantly decreased in IDA as compared to controls. The fetal hemoglobin and ferritin levels were in the normal range in both groups. There was no correlation between maternal and cord blood hepcidin with fetal iron status in IDA. We further analyzed the expression of iron transport genes in the placenta of controls and the IDA group. Under maternal iron insufficiency, the expression of placental iron transporters DMT1, FPN1, and GDF15 was upregulated at the protein level. In IDA, placental GDF15 and ferroportin protein had an association with fetal iron status. These findings confirm that placental iron traffickers respond to maternal iron deficiency by increasing their expression and allowing sufficient iron to pass to the fetus. [ABSTRACT FROM AUTHOR]

In this study, the density, ρ , dynamic viscosity, η , (solid + liquid), SLE and (vapor + liquid), VLE phase equilibria of four binary systems (ionic liquid, IL + water) are determined. Heat capacities, C p of (organic salt + water) mixtures were studied as well. In this work, a series of organic salts namely: 1-mehyl-1-propylmorpholinium bromide, [C 1 C 3 MOR]Br, 1-mehyl-1-butylmorpholinium bromide, [C 1 C 4 MOR]Br, 1-mehyl-1-pentylmorpholinium bromide, [C 1 C 5 MOR]Br and 1-methyl-1-pentylpiperidinium bromide, [C 1 C 5 PIP]Br have been synthesized. The structure of the synthesized compounds were confirmed by 1 H NMR, 13 C NMR and elemental analysis. The thermophysical characterization of pure organic salts, including: temperature of phase transition ( T tr ), enthalpy of phase transition (Δ tr H ), melting temperature ( T m ) and enthalpy of melting (Δ m H ) have been determined using differential scanning microcalorimetry technique ( DSC ) at atmospheric pressure. Additionally, the thermogravimetry technique ( TG / DTA ) was used to determine the decomposition temperature. The influence of the alkyl chain length in the morpholinium cation as well as the cation structure on the physicochemical and thermodynamic properties presented in this work are discussed. [ABSTRACT FROM AUTHOR]

Iron is essential for all mammalian cells, but it is toxic in excess. Our understanding of molecular mechanisms ensuring iron homeostasis at both cellular and systemic levels has dramatically increased over the past 15 years. However, despite major advances in this field, homeostatic regulation of iron in the central nervous system (CNS) requires elucidation. It is unclear how iron moves in the CNS and how its transfer to the CNS across the blood-brain and the blood-cerebrospinal fluid barriers, which separate the CNS from the systemic circulation, is regulated. Increasing evidence indicates the role of iron dysregulation in neuronal cell death observed in neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). ALS is a progressive neurodegenerative disorder characterized by selective cortical czynand spinal motor neuron dysfunction that results from a complex interplay among various pathogenic factors including oxidative stress. The latter is known to strongly affect cellular iron balance, creating a vicious circle to exacerbate oxidative injury. The role of iron in the pathogenesis of ALS is confirmed by therapeutic effects of iron chelation in ALS mouse models. These models are of great importance for deciphering molecular mechanisms of iron accumulation in neurons. Most of them consist of transgenic rodents overexpressing the mutated human superoxide dismutase 1 (SOD1) gene. Mutations in the SOD1 gene constitute one of the most common genetic causes of the inherited form of ALS. However, it should be considered that overexpression of the SOD1 gene usually leads to increased SOD1 enzymatic activity, a condition which does not occur in human pathology and which may itself change the expression of iron metabolism genes. [ABSTRACT FROM AUTHOR]

Thiswork reports the measurements of the vapor pressure, excessenthalpy of mixing, and molar heat capacity for selected {ionic liquid+ water} binary systems. The studied ionic liquids are 1-ethyl-1-methylpiperidiniumethylsulfate, 1-ethyl-1-methylpyrrolidinium ethylsulfate, and 1-ethyl-1-methylmorpholiniumethylsulfate. The isothermal vapor–liquid phase equilibriahave been measured by an ebulliometric method within temperature rangefrom 338.15 to 368.15 K and pressure up to the vapor pressure of purewater. Excess enthalpy was measured with an isothermal titration calorimeterat temperature 298.15 K. Heat capacities have been determined withinthe temperature range from 288.15 to 383.15 K. The influence of temperatureand composition as well as the structure of cation of the studiedionic liquids on the measured properties was assessed. The Redlich–Kistercorrelation was used in order to reduce the huge number of data pointscollected. Finally, thermodynamic modeling with molecular-based PC-SAFTequation of state was performed in order to check predictive capabilitiesof this model as well as to provide some physical insight into mutualionic liquid–water interactions. [ABSTRACT FROM AUTHOR]

The biological interaction between copper and iron is best exemplified by the decreased activity of multicopper ferroxidases under conditions of copper deficiency that limits the availability of iron for erythropoiesis. However, little is known about how copper deficiency affects iron homeostasis through alteration of the activity of other copper-containing proteins, not directly connected with iron metabolism, such as superoxide dismutase 1 (SOD1). This antioxidant enzyme scavenges the superoxide anion, a reactive oxygen species contributing to the toxicity of iron via the Fenton reaction. Here, we analyzed changes in the systemic iron metabolism using an animal model of Menkes disease: copper-deficient mosaic mutant mice with dysfunction of the ATP7A copper transporter. We found that the erythrocytes of these mutants are copper-deficient, display decreased SOD1 activity/expression and have cell membrane abnormalities. In consequence, the mosaic mice show evidence of haemolysis accompanied by haptoglobin-dependent elimination of haemoglobin (Hb) from the circulation, as well as the induction of haem oxygenase 1 (HO1) in the liver and kidney. Moreover, the hepcidin-ferroportin regulatory axis is strongly affected in mosaic mice. These findings indicate that haemolysis is an additional pathogenic factor in a mouse model of Menkes diseases and provides evidence of a new indirect connection between copper deficiency and iron metabolism. [ABSTRACT FROM AUTHOR]

The aim of the study was to establish an optimized protocol of iron dextran administration to pig neonates, which better meets the iron demand for erythropoiesis. Here, we monitored development of red blood cell indices, plasma iron parameters during a 28-day period after birth (till the weaning), following intramuscular administration of different concentrations of iron dextran to suckling piglets. To better assess the iron status we developed a novel mass spectrometry assay to quantify pig plasma levels of the iron-regulatory peptide hormone hepcidin-25. This hormone is predominantly secreted by the liver and acts as a negative regulator of iron absorption and reutilization. The routinely used protocol with high amount of iron resulted in the recovery of piglets from iron deficiency but also in strongly elevated plasma hepcidin-25 levels. A similar protocol with reduced amounts of iron improved hematological status of piglets to the same level while plasma hepcidin-25 levels remained low. These data show that plasma hepcidin-25 levels can guide optimal dosing of iron treatment and pave the way for mixed supplementation of piglets starting with intramuscular injection of iron dextran followed by dietary supplementation, which could be efficient under condition of very low plasma hepcidin-25 level. [ABSTRACT FROM AUTHOR]

HO1 (haem oxygenase 1) and Fpn (ferroportin) are key proteins for iron recycling from senescent red blood cells and therefore play a major role in controlling the bioavailability of iron for erythropoiesis. Although important aspects of iron metabolism in HO1-deficient (Hmox1-/-)mice have already been revealed, little is known about the regulation of Fpn expression and its role in HO1 deficiency. In the present study, we characterize the cellular and systemic factors influencing Fpn expression in Hmox1-/- bone marrow-derived macrophages and in the liver and kidney of Hmox1-/- mice. In Hmox1-/- macrophages, Fpn protein was relatively highly expressed under high levels of hepcidin in culture medium. Similarly, despite high hepatic hepcidin expression, Fpn is still detected in Kupffer cells and is also markedly enhanced at the basolateral membrane of the renal tubules of Hmox1-/- mice. Through the activity of highly expressed Fpn, epithelial cells of the renal tubules probably take over the function of impaired system of tissuemacrophages in recycling iron accumulated in the kidney. Moreover, although we have found increased expression of FLVCR (feline leukaemia virus subgroup C receptor), a haem exporter, in the kidneys of Hmox1-/- mice, haem level was increased in these organs. Furthermore, we show that iron/haemmediated toxicity are responsible for renal injury documented in the kidneys of Hmox1-/- mice. [ABSTRACT FROM AUTHOR]

Abstract: Copper is a trace element that is essential for the normal growth and development of all living organisms. In mammals, the ATP7A Cu-transporting ATPase is a key protein that is required for the maintenance of copper homeostasis. In both humans and mice, the ATP7A protein is coded by the X-linked ATP7A/Atp7a gene. Disturbances in copper metabolism caused by mutations in the ATP7A/Atp7a gene lead to severe metabolic syndromes Menkes disease in humans and the lethal mottled phenotype in mice. Mosaic is one of numerous mottled mutations and may serve as a model for a severe Menkes disease variant. In Menkes patients, mutations in the ATP7A gene often result in a decreased level of the normal ATP7A protein. The aim of this study was to analyse the expression of the Atp7a gene in mosaic mutants in early postnatal development, a critical period for starting copper supplementation therapy in both Menkes patients and mutant mice. Using real-time quantitative RT-PCR, we analysed the expression of the Atp7a gene in the brain, kidney and liver of newborn (P0.5) and suckling (P14) mice. Our results indicate that in mosaic P0.5 mutants, the Atp7a mRNA level is decreased in all analysed organs in comparison with wild-type animals. In two week-old mutants, a significant decrease was observed only in the kidney. In contrast, their hepatic level of Atp7a tended to be higher than in wild-type mice. We speculate that disturbance in the expression of the Atp7a gene and, consequently, change in the copper concentration of the organs, may contribute to the early fatal outcome of mosaic males. [Copyright &y& Elsevier]

Abstract: The pig is born with limited iron supplies. If not supplemented, piglets dramatically loose their body iron stores during the first few days of postnatal life. The aim of this study was to investigate the influence of hepatic iron content on susceptibility of blood cells to oxidative stress. Four 1-day-old and three 7-days-old animals were used in this study. The alkaline version of the comet assay was used to measure DNA damage. As expected, iron body stores of non-supplemented animals decrease significantly during the first 4 days of life. However, no difference in background DNA damage was found between untreated lymphocytes from these two groups of animals, despite the difference in their hepatic iron content. Interestingly, DNA damage induced by H2O2 and X-radiation in lymphocytes taken from 1-day-old piglets was significantly higher than in those taken from 7-days-old animals. In contrast, NaOCl or tert-butyl-hydroxide also induced significant amounts of DNA damage, but no differences between the two groups of piglets were found. Our data show that decreased hepatic iron content corresponds with decreased susceptibility of blood lymphocytes to oxidative stressors. [Copyright &y& Elsevier]

Iron plays an important role in various crucial processes in the body and its deficiency is considered currently as a serious health problem. Thus, iron supplementation strategies for both humans and animals need to be effective and safe. According to our previous studies, zinc-based nanoparticles provide safe, biodegradable, fast and efficient transport system of orally given substances to the tissues. In the current manuscript we present results of a study aimed at investigation of the ZnO nanoparticle-based Fe supplementation system (average size 100 × 250 nm). Nanostructures were orally (gavage) administered to adult mice. Animals were sacrificed at different time points with collection of blood and internal organs for analyses (tissue iron concentration, hepatic level of hepcidin, blood parameters, liver and spleen levels of ferritin, histopathology). Initial experiment was performed to compare the biological effect of doping type (Fe3+ doping vs. a mixture of Fe3+ and Fe2+). Then, the effect of acute/chronic exposure models was determined. The increase in ferritin, along with improved, crucial hematological parameters and lack of the influence on hepcidin expression indicated the chronic application of Fe3+,2+ doped ZnO nanostructures to be the most effective among tested. [ABSTRACT FROM AUTHOR]

The critical function of ferroportin (Fpn) in maintaining iron homeostasis requires complex and multilevel control of its expression. Besides iron-dependent cellular and systemic control of Fpn expression, other metals also seem to be involved in regulating the Fpn gene. Here, we found that copper loading significantly enhanced Fpn transcription in an Nrf2-dependent manner in primary bone-marrow-derived macrophages (BMDMs). However, prolonged copper loading resulted in decreased Fpn protein abundance. Moreover, CuCl2 treatment induced Fpn expression in RAW 264.7 macrophages at both the mRNA and protein level. These data suggest that cell-type-specific regulations have an impact on Fpn protein stability after copper loading. Transcriptional suppression of Fpn after lipopolysaccharide (LPS) treatment contributes to increased iron storage inside macrophages and may result in anemia of inflammation. Here, we observed that in both primary BMDMs and RAW 264.7 macrophages, LPS treatment significantly decreased Fpn mRNA levels, but concomitant CuCl2 stimulation counteracted the transcriptional suppression of Fpn and restored its expression to the control level. Overall, we show that copper loading significantly enhances Fpn transcription in macrophages, while Fpn protein abundance in response to CuCl2 treatment, depending on macrophage type and factors specific to the macrophage population, can influence Fpn regulation in response to copper loading. [ABSTRACT FROM AUTHOR]

Iron is an essential nutrient during all stages of mammalian development. Studies carried out over the last 20 years have provided important insights into cellular and systemic iron metabolism in adult organisms and led to the deciphering of many molecular details of its regulation. However, our knowledge of iron handling in prenatal development has remained remarkably under-appreciated, even though it is critical for the health of both the embryo/fetus and its mother, and has a far-reaching impact in postnatal life. Prenatal development requires a continuous, albeit quantitatively matched with the stage of development, supply of iron to support rapid cell division during embryogenesis in order to meet iron needs for erythropoiesis and to build up hepatic iron stores, (which are the major source of this microelement for the neonate). Here, we provide a concise overview of current knowledge of the role of iron metabolism-related genes in the maintenance of iron homeostasis in pre- and post-implantation development based on studies on transgenic (mainly knock-out) mouse models. Most studies on mice with globally deleted genes do not conclude whether underlying in utero iron disorders or lethality is due to defective placental iron transport or iron misregulation in the embryo/fetus proper (or due to both). Therefore, there is a need of animal models with tissue specific targeted deletion of genes to advance the understanding of prenatal iron metabolism. [ABSTRACT FROM AUTHOR]

Hereditary hemochromatosis (HH) is a genetic disease leading to excessive iron absorption, its accumulation, and oxidative stress induction causing different organ damage, including the heart. The process of cardiac involvement is slow and lasts for years. Cardiac pathology manifests as an impaired diastolic function and cardiac hypertrophy at first and as dilatative cardiomyopathy and heart failure with time. From the moment of heart failure appearance, the prognosis is poor. Therefore, it is crucial to prevent those lesions by upfront therapy at the preclinical phase of the disease. The most useful diagnostic tool for detecting cardiac involvement is echocardiography. However, during an early phase of the disease, when patients do not present severe abnormalities in serum iron parameters and severe symptoms of other organ involvement, heart damage may be overlooked due to the lack of evident signs of cardiac dysfunction. Considerable advancement in echocardiography, with particular attention to speckle tracking echocardiography, allows detecting discrete myocardial abnormalities and planning strategy for further clinical management before the occurrence of substantial heart damage. The review aims to present the current state of knowledge concerning cardiac involvement in HH. In addition, it could help cardiologists and other physicians in their everyday practice with HH patients. [ABSTRACT FROM AUTHOR]

The measurements of the specific activity of natural radioactive isotopes of radium (226Ra), thorium (232Th) and potassium (40K) in chosen samples of imported (China, Finland, Spain, India, Sweden) and Polish (Izerski, Karkonosze, Siedlimowicki, Strzegomski, Strzelinski) granites were performed. The measurements were carried out with 2 × 2" NaI(Tl) scintillation detector. The measured specific activity on natural radioactive isotopes were within the following ranges: 5.8–312 [Bq kg−1], 5.5–189 [Bq kg−1] and 109–1590 [Bq kg−1] for 226Ra, 232Th and 40K, respectively. Obtained concentrations of radioactive isotopes allowed to perform the analysis of the exposure of the humans from the ionizing radiation emitted by the granites. The determination of the exposure consisted in the calculation of absorbed gamma dose rate (D) [nGy h−1] for each sample, which fell in the range between 20 and 511 [nGy h−1], annual effective dose rate (AED) [mSv year−1] ranging between 0.10 and 2.50 [mSv year−1], radium equivalent activity (Raeq) [Bq kg−1] with values between 22 and 570 [Bq kg−1], external and internal hazard indices (Hex) and (Hin) falling in the ranges 0.06−1.53 and 0.08–2.41 respectively, as well as gamma (Iγ) and alpha (Iα), representative level indices with values 0.08–2.0 and 0.029–1.56, respectively. Moreover, obtained results were compared with the international standard values given by the European Commission (EC), the United Nations Scientific Committee on the Effects of Atomic Radiation given in UNSCEAR Reports, and the results of research from other laboratories. [ABSTRACT FROM AUTHOR]

In pigs, iron deficiency anemia (IDA) is the most prevalent deficiency disorder during the early postnatal period, frequently developing into a serious illness. On the other hand, in humans, only low-birth-weight infants, including premature infants, are especially susceptible to developing IDA. In both human and pig neonates, the initial cause of IDA is low birth iron stores. In piglets this shortage of stored iron results mainly from genetic selection over the past few decades for large litter sizes and high birth weights. As a consequence, pregnant sows cannot provide a sufficient amount of iron to the increasing number of developing fetuses. Supplementation with iron is a common practice for the treatment of IDA in piglets. For decades, the preferred procedure for delivering iron supplements during early life stages has been through the intramuscular injection of a large amount of iron dextran. However, this relatively simple therapy, which in general, efficiently corrects IDA, may generate toxic effects, and by inducing hepcidin expression, may decrease bioavailability of supplemental iron. New iron supplements are considered herein with the aim to combine the improvement of hematological status, blunting of hepcidin expression, and minimizing the toxicity of the administered iron. We propose that iron-deficient piglets constitute a convenient animal model for performing pre-clinical studies with iron supplements. [ABSTRACT FROM AUTHOR]