The ferritins: molecular properties, iron storage function and cellular regulation☆

Early indicators for nanoparticle-derived adverse health effects should provide a relative measure for cytotoxicity of nanomaterials in comparison to existing toxicological data. We have therefore evaluated a human mesothelioma and a rodent fibroblast cell line for in vitro cytotoxicity tests using seven industrially important nanoparticles. Their response in terms of metabolic activity and cell proliferation of cultures exposed to 0−30 ppm nanoparticles (μg g-1) was compared to the effects of nontoxic amorphous silica and toxic crocidolite asbestos. Solubility was found to strongly influence the cytotoxic response. The results further revealed a nanoparticle-specific cytotoxic mechanism for uncoated iron oxide and partial detoxification or recovery after treatment with zirconia, ceria, or titania. While in vitro experiments may never replace in vivo studies, the relatively simple cytotoxic tests provide a readily available pre-screening method.

In Vitro Cytotoxicity of Oxide Nanoparticles: Comparison to Asbestos, Silica, and the Effect of Particle Solubility†

Damage from free radicals has been demonstrated in susceptible neuronal populations in cases of Alzheimer disease. In this study, we investigated whether iron, a potent source of the highly reactive hydroxyl radical that is generated by the Fenton reaction with H2O2, might contribute to the source of radicals in Alzheimer disease. We found, using a modified histochemical technique that relies on the formation of mixed valence iron complexes, that redox-active iron is associated with the senile plaques and neurofibrillary tangles—the pathological hallmark lesions of this disease. This lesion-associated iron is able to participate in in situ oxidation and readily catalyzes an H2O2-dependent oxidation. Furthermore, removal of iron was completely effected using deferoxamine, after which iron could be rebound to the lesions. Characterization of the iron-binding site suggests that binding is dependent on available histidine residues and on protein conformation. Taken together, these findings indicate that iron accumulation could be an important contributor toward the oxidative damage of Alzheimer disease.

https://www.pnas.org/content/pnas/94/18/9866.full.pdf

Iron accumulation in Alzheimer disease is a source of redox-generated free radicals.

http://europepmc.org/articles/PMC281418?pdf=render

Iron and infection.

Measurements of serum ferritin were correlated with other hematologic laboratory indexes in 250 hospitalized subjects with anemia or disorders in iron metabolism. A geometric mean value of 4 ng per milliliter was found in 32 patients with uncomplicated iron-deficiency anemia, and one of 2930 ng per milliliter in 23 with iron overload. Among subjects with anemia from causes otherthan iron deficiency, the mean serum ferritin level was increased to 180 ng per milliliter (geometric mean in normal controls, 59 ng per milliliter, with a 95 per cent confidence range of 12 to 300 ng per milliliter), presumably reflecting the transport of red-cell iron to stores. The wide range of values found was shown to be related primarily to the magnitude of body iron stores in each case as evaluated by bone-marrow hemosiderin. In addition, however, inflammation, liver disease and increased red-cell turnover were shown to elevate the serum ferritin concentration to a degree disproportionate to that of iron stores. (N...

A clinical evaluation of serum ferritin as an index of iron stores.

The relationship between serum ferritin concentration and the amount of storage iron has been studied in normal subjects. A high degree of correlation was demonstrated between serum ferritin concentration and storage iron measured by quantitative phlebotomy. The possible advantages of assessing iron stores by using the serum ferritin concentration are discussed.

https://jcp.bmj.com/content/jclinpath/26/10/770.full.pdf

Serum ferritin concentration and iron stores in normal subjects

The concentration of ferritin in serum gives a quantitative measure of the amount of storage iron in normal subjects and those with iron deficiency or overload. The mean level in normal men is 69 ng/ml, compared with 35 ng/ml in normal women. A concentration below 10 ng/ml is associated with a low transferrin saturation and iron-deficient erythropoiesis.

https://www.bmj.com/content/bmj/4/5834/206.full.pdf

M. Worwood

Papers

Serum ferritin concentration and iron stores in normal subjects

Ferritin in the Serum of Normal Subjects and Patients with Iron Deficiency and Iron Overload

Iron in biochemistry and medicine.

Ferritin in serum. Clinical and biochemical implications.

Ferritin in Serum