Benefits and risks of iron supplementation in anemic neonatal pigs.

Iron deficiency is a common health problem. The most severe consequence of this disorder is iron deficiency anemia (IDA), which is considered the most common nutritional deficiency worldwide. Newborn piglets are an ideal model to explore the multifaceted etiology of IDA in mammals, as IDA is the most prevalent deficiency disorder throughout the early postnatal period in this species and frequently develops into a critical illness. Here, we report the very low expression of duodenal iron transporters in pigs during the first days of life. We postulate that this low expression level is why the iron demands of the piglet body are not met by iron absorption during this period. Interestingly, we found that a low level of duodenal divalent metal transporter 1 and ferroportin, two iron transporters located on the apical and basolateral membrane of duodenal absorptive enterocytes, respectively, correlates with abnormally high expression of hepcidin, despite the poor hepatic and overall iron status of these animals. Parenteral iron supplementation by a unique intramuscular administration of large amounts of iron dextran is current practice for the treatment of IDA in piglets. However, the potential toxicity of such supplemental iron implies the necessity for caution when applying this treatment. Here we demonstrate that a modified strategy for iron supplementation of newborn piglets with iron dextran improves the piglets' hematological status, attenuates the induction of hepcidin expression, and minimizes the toxicity of the administered iron.

Hepcidin induction limits mobilisation of splenic iron in a mouse model of secondary iron overload.

Venesection has been proposed as a treatment for hepatic iron overload in a number of chronic liver disorders that are not primarily linked to mutations in iron metabolism genes. Our aim was to analyse the impact of venesection on iron mobilisation in a mouse model of secondary iron overload. C57Bl/6 mice were given oral iron supplementation with or without phlebotomy between day 0 (D0) and D22, and the results were compared to controls without iron overload. We studied serum and tissue iron parameters, mRNA levels of hepcidin1, ferroportin, and transferrin receptor 1, and protein levels of ferroportin in the liver and spleen. On D0, animals with iron overload displayed elevations in iron parameters and hepatic hepcidin1 mRNA. By D22, in the absence of phlebotomies, splenic iron had increased, but transferrin saturation had decreased. This was associated with high hepatic hepcidin1 mRNA, suggesting that iron bioavailability decreased due to splenic iron sequestration through ferroportin protein downregulation. After 22days with phlebotomy treatments, control mice displayed splenic iron mobilisation that compensated for the iron lost due to phlebotomy. In contrast, phlebotomy treatments in mice with iron overload caused anaemia due to inadequate iron mobilisation. In conclusion, our model of secondary iron overload led to decreased plasma iron associated with an increase in hepcidin expression and subsequent restriction of iron export from the spleen. Our data support the importance of managing hepcidin levels before starting venesection therapy in patients with secondary iron overload that are eligible for phlebotomy.