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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]

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]

The aim of this study was to compare the effect of elevated temperatures on the development of cattle embryos cocultured with bovine oviduct epithelial cells (BOECs) and cultured in a KSOMaa medium. Zygotes obtained in vitro were cocultured with BOECs and cultured in KSOMaa (potassium simplex optimised medium modified by amino acids) at a control temperature (38.5℃), and elevated temperatures (40.5℃ and 41℃) for 168 hours. At 38.5℃ there was no significant difference in embryo development between BOEC and KSOMaa treatments. At 40.5℃ embryos cocultured with BOECs developed significantly better compared to the KSOMaa system, as observed at the cleavage rate (73.45±2.45 vs 66.75±1.34%), minimum 8 cell rate (20.36±1.42 vs 16.78±1.48%) and the blastocyst rate (3.13±3.25 vs 0%), (P<0.001). At 41oC there were significant differences in the cleavage rate (62.25±1.72 vs 56.313.47%) and the minimum 8 cell rate (13.06±1.97 vs 9.64±2.14%) in the BOEC coculture system compared to the KSOMaa system (P<0.001), at no differences in the blastocyst rate. In embryos cocultured with BOECs, the hsp70 mRNA expression was higher than in embryos cultured in KSOMaa: 38.5℃-1.42±0.05 vs 0.77±0.04; 40.5℃-3.82±0.04 vs 1.92±0.24; 41℃-6.74±0.20 vs 2.14±0.13, (P<0.001). Also, the HSP70 protein level was higher in embryos cocultured with BOECs than those cultured in KSOMaa: 38.5℃-0.98±0.01 vs 0.17±0.02; 40.5℃-1.96±0.01 vs 0.82±0.01; 41℃-2.45±0.01 vs 1.30±0.01, (P<0.001). This data indicates that bovine embryos cultured at elevated temperatures in the presence of BOECs develop better than embryos cultured in KSOMaa and also that BOECs stimulate embryos to switch on their defence mechanisms to a significantly higher level than in embryos cultured in KSOMaa. [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]

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by degeneration and loss of motor neurons in the spinal cord, brainstem and motor cortex. Up to 10% of ALS cases are inherited (familial, fALS) and associated with mutations, frequently in the superoxide dismutase 1 (SOD1) gene. Rodent transgenic models of ALS are often used to elucidate a complex pathogenesis of this disease. Of importance, both ALS patients and animals carrying mutated human SOD1 gene show symptoms of oxidative stress and iron metabolism misregulation. The aim of our study was to characterize changes in iron metabolism in one of the most commonly used models of ALS - transgenic mice overexpressing human mutated SOD1G93A gene. We analyzed the expression of iron-related genes in asymptomatic, 2-month-old and symptomatic, 4-month-old SOD1G93A mice. In parallel, respective age-matched mice overexpressing human non-mutated SOD1 transgene and control mice were analyzed. We demonstrate that the overexpression of both SOD1 and SOD1G93A genes account for a substantial increase in SOD1 protein levels and activity in selected tissues and that not all the changes in iron metabolism genes expression are specific for the overexpression of the mutated form of SOD1. [ABSTRACT FROM AUTHOR]

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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]

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]

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]

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]

Iron homeostasis consists in providing iron for a variety of biochemical processes and in limiting iron availability for Fenton reaction. Intracellular and systemic iron homeostasis is an important element in the defense against oxidative stress and is controlled by post-transcriptional regulatory mechanism IRP/IRE and hepcidin, a peptide that regulates iron absorption from diet and heme iron release by macrophages. Mutations in hepcidin gene as well as in genes involved in hepcidin regulation lead to the toxic accumulation of iron in the body and exacerbate oxidative stress. Reactive oxygen species influence labile iron pool through the transcriptional and posttranscriptional regulation of ferritin gene and through the release of iron from iron-sulfur proteins and from ferritin degraded in lysosomes. Alcohol-induced oxidative stress down-regulates hepcidin expression, increases iron absorption and leads to the excessive accumulation of iron and oxidative damage in the liver.

Hepcidin is a circulating antimicrobial peptide mainly synthesized in the liver, which has been recently proposed as a factor regulating the uptake of dietary iron and its release by reticuloendothelial macrophages. Hepcidin is a potent mediator of anemia of inflammation. Disrupted hepcidin expression is thought to mediate the pathological effects of mutations in the HFE gene in hereditary hemochromatosis. Discovery of the critical role of hepcidin in iron homeostasis could help in the design of new therapies for some iron metabolism disorders in humans. The aim of this review is to summarize current knowledge about the function and regulation of hepcidin in iron metabolism.

Iron regulatory protein 1 (IRP1) post-transcriptionally regulates the expression of proteins involved in the iron metabolism of mammals. IRP1 is a bifunctional cytosolic protein which can exhibit aconitase activity or bind to iron responsive element (IREs) in the untranslated regions of specific mRNAs. The modulation of IRP1 activities and its consequence for intracellular iron homeostasis is best characterized in rodents and humans. Little is known about IRP1 in farm animals. In this study, we analyzed the two activities of IRP1 in the livers of four farm animal species (cattle, goat, pig and rabbit) and their relationship to hepatic iron content. We found an inverse correlation between spontaneous IRP1 IRE binding activity and non-haem iron content in the liver. Using the electrophoretic mobility shift assay, we showed differential mobility of IRE/IRP1 complexes formed with hepatic cytosolic extracts from various farm animal species. We discuss this observation in relation to a comparative analysis of mammalian IRP1 amino acid sequences.