Quantification of Iron Release from Native Ferritin and Magnetoferritin Induced by Vitamins B2 and C

Abstract

Various pathological processes in humans are associated with biogenic iron accumulation and the mineralization of iron oxide nanoparticles, especially magnetite. Ferritin has been proposed as a precursor to pathological magnetite mineralization. This study quantifies spectroscopically the release of ferrous ions from native ferritin and magnetoferritin as a model system for pathological ferritin in the presence of potent natural reducing agents (vitamins C and B2) over time. Ferrous cations are required for the transformation of ferrihydrite (physiological) into a magnetite (pathological) mineral core and are considered toxic at elevated levels. The study shows a significant difference in the reduction and iron release from native ferritin compared to magnetoferritin for both vitamins. The amount of reduced iron formed from a magnetoferritin mineral core is two to five times higher than from native ferritin. Surprisingly, increasing the concentration of the reducing agent affects only iron release from native ferritin. Magnetoferritin cores with different loading factors seem to be insensitive to different concentrations of vitamins. An alternative hypothesis of human tissue magnetite mineralization and the process of iron-induced pathology is proposed. The results could contribute to evidence of the molecular mechanisms of various iron-related pathologies, including neurodegeneration.

Longitudinal and Transverse Relaxivity Analysis of Native Ferritin and Magnetoferritin at 7 T MRI

“…The basic physicochemical characteristics (LF, D <HYDR> , ζ potential, polydispersity index-PDI) of the NF (horse spleen ferritin) and MF samples are shown in Table 1. The LF, D <HYDR> and ζ potential, including magnetization curves, of the mineral core reduction of NF and MF, induced by vitamins B 2 and C, have recently been published by this group [15]. Summarizing this earlier work, the hydrodynamic diameter D <HYDR> , determined by dynamic light scattering (DLS), has higher values of MF than NF, probably due to the aggregation of MFs as a consequence of their increased dipole-dipole interactions.…”

“…This process is hazardous, resulting in hydrogen peroxide overproduction and damage to antioxidants, including iron scavengers, peroxidases, and iron storage proteins, such as ferritin [13], which can lead to cancer [14]. From these studies, together with recent work on reduction of the ferritin nucleus [15], it appears that iron accumulation and mineralization is at least an accomplice of pathology. However, at present, it is still not known whether the formation of iron oxide aggregates is the cause or the result of pathology.…”

The Impact of Redox, Hydrolysis and Dehydration Chemistry on the Structural and Magnetic Properties of Magnetoferritin Prepared in Variable Thermal Conditions

“…The iron core in the prepared MFer undergoes post-synthesis transformations associated with redox reactions in response to potential external effects of oxygen, changes in temperature or pH in the liquid state. This apparent lack of sensitivity causes the reactivity of MFer colloidal solutions, especially in interactions with other substances: vitamins [25], dangerous molecules such as polychlorinated biphenyls (PCBs) [49] or hydrogen peroxide (H 2 O 2 ) [50], schematically illustrated in Figure 8. Ascorbic acid and riboflavin, as electron donors, can reduce ferritin and the MFer iron core to ferrous ions [25].…”

“…This apparent lack of sensitivity causes the reactivity of MFer colloidal solutions, especially in interactions with other substances: vitamins [25], dangerous molecules such as polychlorinated biphenyls (PCBs) [49] or hydrogen peroxide (H 2 O 2 ) [50], schematically illustrated in Figure 8. Ascorbic acid and riboflavin, as electron donors, can reduce ferritin and the MFer iron core to ferrous ions [25]. Vitamins can increase the bioavailability of iron for oral iron supplementation-based therapy by fine-tuning the optimal vitamin-to-iron ratio to reduce the harmful gastrointestinal side effects of iron [25,51].…”

“…All factors and metabolic pathways that affected the in vivo crystallization of this mineral have not been fully revealed. A combination of iron overloading, temperature, pressure, pH value, magnetism, electromagnetic radiation, reaction kinetics, the presence of various molecules, oxidants/reductants (flavonoids, vitamins, superoxide, Aβ peptide) [21][22][23][24][25], metabolic imbalances, genetics (transcription, translation or folding deficiencies), structural or functional disorders, and the role of short-and longterm interactions (Levinthal paradox) [26] was suggested. Simple magnetotactic bacteria, Magnetospirillum magnetotacticum, can naturally form highly monodisperse single-domain magnetite nanocrystals [27].…”