The effects of iron deficient and high iron diets on SARS-CoV-2 lung infection and disease.

Introduction: The severity of Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often dictated by a range of comorbidities. A considerable literature suggests iron deficiency and iron overload may contribute to increased infection, inflammation and disease severity, although direct causal relationships have been difficult to establish.

Methods: Here we generate iron deficient and iron loaded C57BL/6 J mice by feeding standard low and high iron diets, with mice on a normal iron diet representing controls.

A Decrease in Maternal Iron Levels Is the Predominant Factor Suppressing Hepcidin during Pregnancy in Mice.

In order to supply adequate iron during pregnancy, the levels of the iron regulatory hormone hepcidin in the maternal circulation are suppressed, thereby increasing dietary iron absorption and storage iron release. Whether this decrease in maternal hepcidin is caused by changes in factors known to regulate hepcidin expression, or by other unidentified pregnancy factors, is not known. To investigate this, we examined iron parameters during pregnancy in mice.

The biology of mammalian multi-copper ferroxidases.

The mammalian multicopper ferroxidases (MCFs) ceruloplasmin (CP), hephaestin (HEPH) and zyklopen (ZP) comprise a family of conserved enzymes that are essential for body iron homeostasis. Each of these enzymes contains six biosynthetically incorporated copper atoms which act as intermediate electron acceptors, and the oxidation of iron is associated with the four electron reduction of dioxygen to generate two water molecules. CP occurs in both a secreted and GPI-linked (membrane-bound) form, while HEPH and ZP each contain a single C-terminal transmembrane domain.

Supplementation with Sucrosomial® iron leads to favourable changes in the intestinal microbiome when compared to ferrous sulfate in mice.

Iron deficiency is one of the most common nutritional deficiencies worldwide and is often treated with oral iron supplements. However, commonly used supplements, including those based on ferrous iron salts, are associated with gastrointestinal side effects and unfavorable changes in the intestinal microbiome. Sucrosomial® iron is a novel iron formulation that is effective at treating iron deficiency, and with fewer gastrointestinal side effects, yet its effect on the gut microbiome has not been examined previously.

A Novel Ferritin-Core Analog Is a Safe and Effective Alternative to Oral Ferrous Iron for Treating Iron Deficiency during Pregnancy in Mice.

Background: Many women enter pregnancy with iron stores that are insufficient to maintain maternal iron balance and support fetal development and consequently, often require iron supplements. However, the side effects associated with many currently available iron supplements can limit compliance.

Objective: This study aimed to test the safety and efficacy of a novel nanoparticulate iron supplement, a dietary ferritin analog termed iron hydroxide adipate tartrate (IHAT), in pregnant mice.

The Placental Ferroxidase Zyklopen Is Not Essential for Iron Transport to the Fetus in Mice.

Background: The ferroxidase zyklopen (Zp) has been implicated in the placental transfer of iron to the fetus. However, the evidence for this is largely circumstantial.

Objectives: This study aimed to determine whether Zp is essential for placental iron transfer.

Dietary iron absorption during early postnatal life.

Inadequate iron levels during early life can have adverse consequences for the developing infant. Iron deficiency during this critical period of growth can affect brain development and cognitive function, problems that can be lifelong despite subsequent correction of the iron deficit. Therefore, it is critical that the suckling infant has sufficient iron for their developmental needs.

Circulating iron levels influence the regulation of hepcidin following stimulated erythropoiesis.

The stimulation of erythrocyte formation increases the demand for iron by the bone marrow and this in turn may affect the levels of circulating diferric transferrin. As this molecule influences the production of the iron regulatory hormone hepcidin, we hypothesized that erythropoiesis-driven changes in diferric transferrin levels could contribute to the decrease in hepcidin observed following the administration of erythropoietin. To examine this, we treated mice with erythropoietin and examined diferric transferrin at various time points up to 18 hours.