Iron Chelator or Iron Supplement Consumption in COVID-19? The Role of Iron with Severity Infection

Control of oxidative stress in the bone marrow (BM) is key for maintaining the interplay between self-renewal, proliferation, and differentiation of hematopoietic cells. Breakdown of this regulation can lead to diseases characterized by BM failure such as the myelodysplastic syndromes (MDS). To better understand the role of oxidative stress in MDS development, we compared protein carbonylation as an indicator of oxidative stress in the BM of patients with MDS and control subjects, and also patients with MDS under treatment with the iron chelator deferasirox (DFX). As expected, differences in the pattern of protein carbonylation were observed in BM samples between MDS patients and controls, with an increase in protein carbonylation in the former. Strikingly, patients under DFX treatment had lower levels of protein carbonylation in BM with respect to untreated patients. Proteomic analysis identified four proteins with high carbonylation levels in MDS BM cells. Finally, as oxidative stress-related signaling pathways can modulate the cell cycle through p53, we analyzed the expression of the p53 target gene p21 in BM cells, finding that it was significantly upregulated in patients with MDS and was significantly downregulated after DFX treatment. Overall, our results suggest that the fine-tuning of oxidative stress levels in the BM of patients with MDS might control malignant progression.

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Conjugation of Hydroxyethyl Starch to Desferrioxamine (DFO) Modulates the Dual Role of DFO in Yersinia enterocolitica Infection

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.7.3.457-462.2000 ◽

2000 ◽

Vol 7 (3) ◽

pp. 457-462 ◽

Cited By ~ 5

Author(s):

Sören Schubert ◽

Ingo B. Autenrieth

Keyword(s):

Yersinia Enterocolitica ◽

Hydroxyethyl Starch ◽

Growth Promotion ◽

Iron Chelator ◽

Dual Role ◽

Host Cells ◽

Immunosuppressive Action

ABSTRACT The iron chelator desferrioxamine (DFO) B is widely used in the therapy of patients with iron overload. As a side effect, DFO may favor the occurrence of fulminant Yersinia infections. Previous work from our laboratory showed that this might be due to a dual role of DFO: growth promotion of the pathogen and immunosuppression of the host. In this study, we sought to determine whether conjugation of DFO to hydroxyethyl starch (HES-DFO) may prevent exacerbation ofYersinia infection in mice. We found HES-DFO to promote neither growth of Yersinia enterocolitica nor mitogen-induced T-cell proliferation and gamma interferon production by T cells in vitro. Nevertheless, in vivo HES-DFO promoted growth ofY. enterocolitica possibly due to cleavage of HES and release of DFO. The pretreatment of mice with DFO resulted in death of all mice 2 to 5 days after application of a normally sublethal inoculum of Y. enterocolitica, while none of the mice pretreated with HES-DFO died within the first 7 days postinfection. However, some of the HES-DFO-treated mice died 8 to 14 days postinfection. Thus, due to the delayed in vivo effect HES-DFO failed to triggerYersinia-induced septic shock, which accounts for early mortality in DFO-associated septicemia. Moreover, our data suggest that DFO needs to be taken up by host cells in order to exert its immunosuppressive action. These results strongly suggest that HES-DFO might be a favorable drug with fewer side effects than DFO in terms of DFO-promoted fulminant infections.

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Role of iron in T cell activation: Th1 clones differ from TH2 clones in their sensitivity to inhibition of DNA synthesis caused by IGG mabs against the transferrin receptor and the iron chelator deferoxamine

Cellular Immunology ◽

10.1016/0008-8749(91)90336-a ◽

1991 ◽

Vol 134 (1) ◽

pp. 126-137 ◽

Cited By ~ 42

Author(s):

John A. Thorson ◽

Kevin M. Smith ◽

Francisco Gomez ◽

Paul W. Naumann ◽

John D. Kemp

Keyword(s):

T Cell ◽

Dna Synthesis ◽

T Cell Activation ◽

Transferrin Receptor ◽

Cell Activation ◽

Iron Chelator ◽

Inhibition Of Dna Synthesis ◽

Iron Chelator Deferoxamine

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Acute iron overload: the role of spermine as endogenous low molecular weight iron chelator

Journal of Hepatology ◽

10.1016/s0168-8278(01)81031-x ◽

2001 ◽

Vol 34 ◽

pp. 47-48 ◽

Cited By ~ 1

Author(s):

D.D. Pavlović ◽

G. Kocić ◽

G. Bjelaković ◽

D. Sokolović ◽

B. Djindjić

Keyword(s):

Molecular Weight ◽

Iron Overload ◽

Iron Chelator ◽

Low Molecular Weight ◽

Low Molecular Weight Iron

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Targeting Pro-Oxidant Iron with Deferoxamine as a Treatment for Ischemic Stroke: Safety and Optimal Dose Selection in a Randomized Clinical Trial

Antioxidants ◽

10.3390/antiox10081270 ◽

2021 ◽

Vol 10 (8) ◽

pp. 1270

Author(s):

Mònica Millán ◽

Núria DeGregorio-Rocasolano ◽

Natàlia Pérez de la Ossa ◽

Sílvia Reverté ◽

Joan Costa ◽

...

Keyword(s):

Ischemic Stroke ◽

Optimal Dose ◽

Iron Chelator ◽

Good Clinical Outcome ◽

Dose Selection ◽

Iron Saturation ◽

Deferoxamine Mesylate ◽

The Impact ◽

New Evidence

A role of iron as a target to prevent stroke-induced neurodegeneration has been recently revisited due to new evidence showing that ferroptosis inhibitors are protective in experimental ischemic stroke and might be therapeutic in other neurodegenerative brain pathologies. Ferroptosis is a new form of programmed cell death attributed to an overwhelming lipidic peroxidation due to excessive free iron and reactive oxygen species (ROS). This study aims to evaluate the safety and tolerability and to explore the therapeutic efficacy of the iron chelator and antioxidant deferoxamine mesylate (DFO) in ischemic stroke patients. Administration of placebo or a single DFO bolus followed by a 72 h continuous infusion of three escalating doses was initiated during the tPA infusion, and the impact on blood transferrin iron was determined. Primary endpoint was safety and tolerability, and secondary endpoint was good clinical outcome (clinicalTrials.gov NCT00777140). DFO was found safe as adverse effects were not different between placebo and DFO arms. DFO (40–60 mg/Kg/day) reduced the iron saturation of blood transferrin. A trend to efficacy was observed in patients with moderate-severe ischemic stroke (NIHSS > 7) treated with DFO 40–60 mg/Kg/day. A good outcome was observed at day 90 in 31% of placebo vs. 50–58% of the 40–60 mg/Kg/day DFO-treated patients.

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Role of iron in breath holding spells and effect of iron therapy in children

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20214160 ◽

2021 ◽

Vol 8 (11) ◽

pp. 1861

Author(s):

Mohmad Saleem Chesti ◽

Shilakha Chaman ◽

Mudasir Nazir

Keyword(s):

Iron Deficiency ◽

Serum Ferritin ◽

Serum Iron ◽

Significant Rise ◽

Hemoglobin Level ◽

Iron Therapy ◽

Deficiency Anemia ◽

Breath Holding ◽

Iron Supplement

Background: Breath holding spells (BHS) are paroxysmal events resulting from painful stimulus or emotional event resulting in forceful crying, occur in children’s aged between 6 months to 6 years. To assess the role of iron in breath holding spells (BHS) and to assess the efficiency of iron therapy in reducing frequency of BHS.Methods: This was a prospective, interventional study conducted at GMC baramulla. A total of 70 patients between the ages of 6 months and 5 years with breath holding spells with iron deficiency and iron deficiency anemia were studied. After giving them iron therapy for 6 and 12 weeks, they were assessed for the improvement in their anemia and its impact on the frequency of breath holding spells.Results: Seventy children with breath holding spells were studied prospectively. Forty (57.15%) cases were males and 30 (42.85%) females. There was a statistically significant rise in the hemoglobin level, serum ferritin, serum iron with 6 and12 weeks of iron therapy (p<0.001). This rise in the hemoglobin level serum ferritin and serum iron was associated with a statistically significant fall in the frequency of breath holding spells with 6 and 12 weeks of iron therapy (p<0.001).Conclusions: iron supplement is effective in reducing the frequency of breath holding spells and thus iron has role in BHS.

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Role of H2O2and heme-containing O2sensors in hypoxic regulation of tyrosine hydroxylase gene expression

AJP Cell Physiology ◽

10.1152/ajpcell.1998.274.1.c167 ◽

1998 ◽

Vol 274 (1) ◽

pp. C167-C174 ◽

Cited By ~ 56

Author(s):

Sandra L. Kroll ◽

Maria F. Czyzyk-Krzeska

Keyword(s):

Gene Expression ◽

Tyrosine Hydroxylase ◽

Iron Chelator ◽

Pc 12 Cells ◽

Hypoxic Induction ◽

Antioxidant Agent ◽

Rate Limiting ◽

Hypoxia Treatment ◽

Th Mrna

In the current study, we investigated links between O2-regulated H2O2formation and the hypoxic induction of mRNA for tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine synthesis, in O2-sensitive PC-12 cells. During exposure of PC-12 cells to 5% O2, H2O2concentration decreased by 40% as measured with 2′,7′-dichlorofluorescein (DCF). Treatment with H2O2reduced TH mRNA during normoxia and prevented the induction of TH mRNA during hypoxia. Treatment with catalase or N-(2-mercaptopropionyl)-glycine, a reducing antioxidant agent that decreases H2O2concentration, also induced TH mRNA. Deferoxamine (DF), an iron chelator, failed to affect H2O2formation but induced TH mRNA in normoxia and hypoxia. CoCl2led to a decrease in H2O2at 20 h of treatment but induced TH mRNA during normoxia and hypoxia before it affected H2O2. In conclusion, TH gene expression correlates inversely with H2O2formation. DF and Co2+seem to affect TH gene expression in the mechanism downstream from the H2O2formation rather than by interfering with the H2O2-generating activity of the O2sensor.

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Role of iron in postischemic microvascular injury

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1989.256.5.h1472 ◽

1989 ◽

Vol 256 (5) ◽

pp. H1472-H1477 ◽

Cited By ~ 4

Author(s):

J. K. Smith ◽

D. L. Carden ◽

M. B. Grisham ◽

D. N. Granger ◽

R. J. Korthuis

Keyword(s):

Xanthine Oxidase ◽

Vascular Permeability ◽

Ischemia Reperfusion ◽

Iron Chelator ◽

Solvent Drag ◽

Microvascular Injury ◽

Iron Binding Protein ◽

Oxidant Production ◽

Permeability Increase

Iron-catalyzed formation of hydroxyl radicals has been postulated to occur during reperfusion of ischemic tissues. To assess the role of iron-catalyzed oxidant production in ischemia/reperfusion (I/R) injury to skeletal muscle, we examined the effects of deferoxamine (an iron chelator) and apotransferrin (an iron-binding protein) on the increased vascular permeability produced by I/R in isolated, pump-perfused rat hindquarters. Solvent drag reflection coefficients (sigma) were measured in hindquarters subjected to 2 h of ischemia and 30 min of reperfusion with either no pretreatment, pretreatment with 50 mg/kg deferoxamine, 200 mg/kg apotransferrin, or iron-loaded deferoxamine (50 mg/kg). I/R alone was associated with an increase in vascular permeability as indicated by the significantly lower estimates of sigma obtained after I/R (0.68 +/- 0.03) compared with those obtained in nonischemic preparations (0.82 +/- 0.02). Pretreatment with deferoxamine or apotransferrin attenuated this permeability increase (sigma = 0.83 +/- 0.03 and 0.86 +/- 0.02, respectively), whereas pretreatment with iron-loaded deferoxamine afforded no protection (sigma = 0.71 +/- 0.02). These findings are consistent with the hypothesis that iron-catalyzed oxidant production is important in the genesis of microvascular injury following I/R. Since the enzyme xanthine oxidase has been implicated as a major source of oxidants generated during reperfusion, we also measured tissue levels of xanthine oxidase and xanthine dehydrogenase in muscle samples obtained from the same hindquarters in which we measured permeability changes.(ABSTRACT TRUNCATED AT 250 WORDS)

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