Disorder of Iron Metabolism as a Universal Pathogenetic Factor in Damage to Organs and Systems in Covid-19

Relevance. The pathogenesis of COVID-19 remains one of the most pressing. The literature discusses the role of iron as a factor supporting inflammatory processes, hypercoagulability and microcirculation crisis in severe COVID-19.The aim of study. was to identify changes in iron metabolism in patients with severe COVID-19 and hyperferritinemia.Material and methods. In this study, we used a content analysis of available scientific publications and our own observations of the peculiarities of the clinical picture and laboratory parameters in patients with a severe course of COVID-19 who had hyperferretinemia at the height of the disease. The main group consisted of 30 patients hospitalized in the Department of Anesthesiology, Resuscitation and Intensive Care of N.A. Semashko City clinical Hospital No. 38 with the diagnosis COVID-19, bilateral polysegmental pneumonia, severe course and hyperferritinemia. The diagnosis of a new coronavirus infection was confirmed by visualization of bilateral viral lung lesions with chest CT-scan, positive PCR test for SARS-CoV-2 and the presence of immunoglobulins to SARS-CoV-2. The control group consisted of 20 healthy volunteers. The study evaluated the biochemical parameters of iron metabolism, fibrinolysis and markers of inflammation. Changes associated with impaired iron metabolism were assessed by the level of serum iron, transferrin, daily and induced iron excretion in the urine. Statistical processing was carried out using nonparametric methods.Results. All patients with severe COVID-19 and hyperferritinemia showed signs of impaired iron metabolism, inflammation and fibrinolysis — a decrease in the level of transferrin (p<0.001), serum iron (p><0.005), albumin (p><0.001), lymphocytes (p><0.001) and an increase in leukocytes (p><0.001), neutrophils (p><0.001), CRP (p><0.005), IL-6 (p><0.001), D-dimer (p><0.005), daily urinary iron excretion (p><0.005) and induced urinary iron excretion (p><0.001). Conclusions The study showed that in the pathogenesis of the severe course of COVID-19, there is a violation of iron metabolism and the presence of a free iron fraction. The appearance of free iron can be caused by damage to cells with the “release” of iron from cytochromes, myoglobin, hemoglobin, or violation of the binding of iron to transferrin, which may be the result of a change in the protein structure or violation of the oxidation of iron to the trivalent state. When assessing the degree of viral effect on the body, one should take into account the effect of various regulators of iron metabolism, as well as an assessment of the level of free iron not associated with transferrin. Keywords: new coronavirus infection, COVID-19, SARS-CoV-2, iron metabolism, free iron, ferritin, transferrin, NTBI, nontransferrin bound iron>˂0.001), serum iron (p˂0.005), albumin (p˂0.001), lymphocytes (p˂0.001) and an increase in leukocytes (p˂0.001), neutrophils (p˂0.001), CRP (p˂0.005), IL-6 (p˂0.001), D-dimer (p˂0.005), daily urinary iron excretion (p˂0.005) and induced urinary iron excretion (p˂0.001).Conclusions. The study showed that in the pathogenesis of the severe course of COVID-19, there is a violation of iron metabolism and the presence of a free iron fraction. The appearance of free iron can be caused by damage to cells with the “release” of iron from cytochromes, myoglobin, hemoglobin, or violation of the binding of iron to transferrin, which may be the result of a change in the protein structure or violation of the oxidation of iron to the trivalent state. When assessing the degree of viral effect on the body, one should take into account the effect of various regulators of iron metabolism, as well as an assessment of the level of free iron not associated with transferrin.

Iron Chemical Analysis of Spodosols to Date Last Pleistocene-Holocene. The Example of the Italian Central Alps.

&lt;p&gt;The deglaciation of the Italian Central Alps is still discussed and not well known, especially when we consider the Late Pleistocene-Early Holocene. This study will use different fraction of the iron content of paleo-spodosols to date the time of the deglaciation of three areas in the Central Italian Alps (Gavia, Stelvio and Val Viola). Relying on a first soil distribution analysis and on geomorphological evidences, we opened and described 24 soil pits and from each A and B horizon we collected at least 1 kg of sample to do some basic soil physical analysis: granulometry, water content, pH and loss on ignition. The oxalate extractable iron fraction and the dithionite extractable iron fraction have been determined with standard lab procedures, the total iron content has been determined using a SEM/EDX analysis. We calculated the Iron Crystallinity Ratio, defined as the difference between the dithionite extractable iron fraction and the oxalate extractable iron fraction, normalized on the total iron content. The Iron Crystallinity Ratio gives us a relative age of the soil formation: using data from radiocarbon dating and from cosmogenic dating, we calibrated the Iron Crystallinity Ratio with absolute ages. With the obtained functions, which showed a good fitting, we calculated ages between 15809 years and 5490 years in the Gavia area, between 11760 years and 7237 years in the Stelvio area and between 14668 years and 7096 years in the Val Viola area.&lt;/p&gt;

Positive effects of ferric iron on the systemic efficacy of nephrilin peptide in burn trauma

Introduction: Nephrilin peptide is a designed inhibitor of Rictor complex (also known as mTORC2), an evolutionarily conserved assembly believed to modulate responses to cellular stress. We previously demonstrated the ability of nephrilin peptide to suppress neuroinflammation, loss of body mass, glycaemic control and kidney function in a rat scald model, as well as sepsis mortality in a mouse model. The present study explores the effect of nephrilin plus iron formulations on clinically relevant outcomes in the rat scald model. Methods: Animals were treated with nephrilin by subcutaneous bolus injection on post-burn days 1–7. Equimolar ferric iron in the formulation improved the positive systemic effects of nephrilin on kidney function, glycaemic control, oxidative stress, early hyperinflammation, late inflammasome activation, hyperangiogenesis and body mass, all variables previously shown to bear upon clinically relevant burn injury outcomes. The sparing effects of nephrilin-iron were demonstrated in both sexes. Discussion: Surprisingly, optimum daily treatment doses were in the range of 2–4 mg/kg, while 8 mg/kg was less effective, suggesting the possibility of marginal pro-oxidant effects from the ‘free’ iron fraction. Thus, although ferric iron in the nephrilin formulation is clearly helpful, care must be exercised to select an optimum treatment dose. Conclusion: Iron increases the efficacy of nephrilin peptide in burns.

FRAKSI BESI DAN PENGARUHNYA TERHADAP KELARUTAN POSFOR DI LAHAN RAWA (Iron Fraction And Its Effect On Posforning Sustainability In Rawa Land)

ABSTRACTAbout 20 million Ha of tidal swampare found in Indonesia,6.7 million ha of them are acid sulphatesoils which associated with peatland.Most of soil in tidal swamp are rich in iron, it potentialy toxicto the plant. We critically examine the presence of peat matter as surface layer to iron fraction andthe role of ferrous to phosphorus (P) solubility in soil.Iron fractions analyzed in acid sulphate soil,peaty acid sulphate soil, shallow peatland, shallow peatland which all of peat layers were removedand shallow peatland which partially of peat layers were removed. Most of iron fraction in tidalswampland which covered by peat layer is organic-Fe form, the presence of peat layer on surfacelayer caused no correlation between Fe and P in soil.Key words : Acid sulphate soil, Iron, Peatland, Phosphorus andTidal swampland

Comparison of iron fractions on the regulated and restored parts of the Rudnia River (NE Poland)

Hydrochemical investigations focusing on different iron fractions were conducted in 2007 from January to December on two parts (regulated and restored) of the small lowland Rudnia River in north-eastern Poland. Concentrations of the total iron (TFe) in the water of the Rudnia River ranged from 582 μg dm-3 up to 3646 μg dm-3, and their elevated values are clearly the result of their complex binding with organic matter originating from the peat-mineral catchment of the river. Regardless of the season, in the upper part of the river (regulated channel) higher concentrations of all iron fractions than in the restored river section were observed. All tests on iron fractions showed a clear seasonal variability on both river channel parts. Higher TFe concentrations were typical for the regulated part of the river in autumn or winter, and lower in spring for the restored river channel section. For the whole of the investigated period and regardless of the season, particulate iron fraction (PFe) represented a higher proportion of TFe in the regulated channel than in the restored one. PFe constituted up to 60% TFe, on average, while the other two fractions about 20% of TFe each. However, dissolved reactive iron fraction (DRFe) made up a larger percentage of TFe than organic soluble fraction (DOFe) of iron within the year. The maximum percentage of DOFe fraction outside the growing season was caused by iron release from organic complexes and elevated concentrations of dissolved organic carbon (DOC) derived from wetlands.

Measured versus Calculated Latent Iron Binding Capacity in Plasma of Newborns

Iron overload as well as iron deficiency may play a role in the pathogenesis of diseases in the newborn and infant and therefore knowledge of the iron status is essential. Using an automated method for the determination of plasma latent iron-binding capacity (LIBC) we measured the LIBC in 20 full term and 20 preterm babies and 20 adults. LIBC was also calculated from transferrin and iron concentration. The measured LIBC strongly deviated from calculated LIBC in some samples and in seven of 20 preterm babies no LIBC could be detected, suggesting the presence of non-protein-bound iron fraction. The results suggest that in the neonate calculated LIBC overestimate the ability of the plasma to bind excessive iron.

Impairment of macrophage functions after ingestion of Plasmodium falciparum-infected erythrocytes or isolated malarial pigment.

Human monocyte-derived macrophages ingest diamide-treated red blood cells (RBC), anti-D immunoglobulin (Ig)G-opsonized RBC, or Plasmodium falciparum ring-stage parasitized RBC (RPRBC), degrade ingested hemoglobin rapidly, and can repeat the phagocytic cycle. Monocytes fed with trophozoite-parasitized RBC (TPRBC), which contain malarial pigment, or fed with isolated pigment are virtually unable to degrade the ingested material and to repeat the phagocytic cycle. Monocytes fed with pigment display a long-lasting oxidative burst that does not occur when they phagocytose diamide-treated RBC or RPRBC. The phorbol myristate acetate-elicited oxidative burst is irreversibly suppressed in monocytes fed with TPRBC or pigment, but not in monocytes fed with diamide-treated or IgG-opsonized RBC. This pattern of inhibition of phagocytosis and oxidative burst suggests that malarial pigment is responsible for the toxic effects. Pigment iron released in the monocyte phagolysosome may be the responsible element. 3% of total pigment iron is labile and easily detached under conditions simulating the internal environment of the phagolysosome, i.e., pH 5.5 and 10 microM H2O2. Iron liberated from pigment could account for the lipid peroxidation and increased production of malondialdehyde observed in monocytes fed with pigment or in RBC ghosts and liposomes incubated at pH 6.5 in presence of pigment and low amounts of H2O2. Removal of the labile iron fraction from pigment by repeated treatments with 0.1 mM H2O2 at pH 5.5 reduces pigment toxicity. It is suggested that iron released from ingested pigment is responsible for the intoxication of monocytes. In acute and chronic falciparum infections, circulating and tissue-resident phagocytes are seen filled with TPRBC and pigment particles over long periods of time. Moreover, human monocytes previously fed with TPRBC are unable to neutralize pathogenic bacteria, fungi, and tumor cells, and macrophage responses decline during the course of human and animal malaria. The present results may offer a mechanistic explanation for depression of cellular immunity in malaria.