scholarly journals Ferrochelatase Deficiency Abrogated the Enhancement of Aminolevulinic Acid‐mediated ProtoporphyrinIXby Iron Chelator Deferoxamine

2019 ◽  
Author(s):  
Pratheeba Palasuberniam ◽  
Daniel Kraus ◽  
Matthew Mansi ◽  
Alexander Braun ◽  
Richard Howley ◽  
...  
Keyword(s):  
Aminolevulinic Acid ◽  
Iron Chelator ◽  
Iron Chelator Deferoxamine

scholarly journals Analysis of yggX and gshA Mutants Provides Insights into the Labile Iron Pool in Salmonella enterica

2008 ◽  
Vol 190 (23) ◽  
pp. 7608-7613 ◽  
Author(s):  
Michael P. Thorgersen ◽  
Diana M. Downs
Keyword(s):  
Salmonella Enterica ◽  
Iron Chelator ◽  
Fenton Chemistry ◽  
Labile Iron Pool ◽  
Growth Defects ◽  
Labile Iron ◽  
Iron Pool ◽  
Mutant Phenotypes ◽  
Permeable Iron ◽  
Iron Chelator Deferoxamine

ABSTRACT Strains of Salmonella enterica lacking YggX and the cellular reductant glutathione exhibit defects similar to those resulting from iron deficiency and oxidative stress. Mutant strains are sensitive to hydrogen peroxide and superoxide, deregulate the expression of the Fur-regulated gene entB, and fail to grow on succinate medium. Suppression of some yggX gshA mutant phenotypes by the cell-permeable iron chelator deferoxamine allowed the conclusion that increased levels of cellular Fenton chemistry played a role in the growth defects. The data presented are consistent with a scenario in which glutathione acts as a physiological chelator of the labile iron pool and in which YggX acts upstream of the labile iron pool by preventing superoxide toxicity.

Oxygen free radical-mediated selective endothelial dysfunction in isolated coronary artery

1992 ◽  
Vol 262 (3) ◽  
pp. H806-H812 ◽  
Author(s):  
K. Todoki ◽  
E. Okabe ◽  
T. Kiyose ◽  
T. Sekishita ◽  
H. Ito
Keyword(s):  
Lipid Peroxidation ◽  
Superoxide Dismutase ◽  
Free Radicals ◽  
Free Radical ◽  
Coronary Artery ◽  
Iron Chelator ◽  
Oxygen Free Radical ◽  
Alpha Tocopherol ◽  
Endothelium Dependent Relaxation ◽  
Iron Chelator Deferoxamine

To understand the direct involvement of free radicals causing reduction in endothelium-dependent relaxation of isolated canine coronary ring preparations, this study was undertaken to examine the effect of free radicals generated from dihydroxy fumarate (DHF) plus Fe(3+)-ADP or from H2O2 plus FeSO4. The vasodilators (acetylcholine, bradykinin, A23187, and nitroglycerin) were given after DHF/Fe(3+)-ADP or H2O2/FeSO4 was removed from the organ chamber. The earlier DHF/Fe(3+)-ADP exposure produced an attenuation of the relaxation of the rings induced by acetylcholine, bradykinin, or A23187 but not of the relaxation induced by nitroglycerin. The observed effect of previous DHF/Fe(3+)-ADP exposure was significantly protected in the vessels isolated from the dogs treated with alpha-tocopherol. In the experiments for assessing the effect of various scavengers, 1O2 scavenger histidine or iron chelator deferoxamine effectively protected the attenuation induced by DHF/Fe(3+)-ADP exposure of the relaxation elicited by acetylcholine; superoxide dismutase (SOD), catalase, or dimethyl sulfoxide (DMSO) had no effect on this system. Furthermore, the relaxation elicited by acetylcholine, but not nitroglycerin, was significantly attenuated by the earlier exposure to .OH generated by Fenton's reagent (H2O2+FeSO4); the attenuation was significantly protected by DMSO. These results are consistent with the view that .OH, 1O2, and/or iron-dependent reactive species selectively damage endothelium-dependent relaxation as opposed to endothelium-independent relaxation in endothelium-intact coronary ring preparations. It is also postulated that lipid peroxidation may be responsible for this effect.

scholarly journals A Novel Star Like Eight-Arm Polyethylene Glycol-Deferoxamine Conjugate for Iron Overload Therapy

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 329
Author(s):  
Bohong Yu ◽  
Yinxian Yang ◽  
Qi Liu ◽  
Aiyan Zhan ◽  
Yang Yang ◽  
...  
Keyword(s):  
Polyethylene Glycol ◽  
Iron Overload ◽  
Iron Chelator ◽  
Iron Chelators ◽  
Iron Binding ◽  
Binding Ability ◽  
Amide Bonds ◽  
Plasma Half Life ◽  
Iron Chelator Deferoxamine

The traditional iron chelator deferoxamine (DFO) has been widely used in the treatment of iron overload disease. However, DFO has congenital disadvantages, including a very short circular time and non-negligible toxicity. Herein, we designed a novel multi-arm conjugate for prolonging DFO duration in vivo and reducing cytotoxicity. The star-like 8-arm-polyethylene glycol (8-arm-PEG) was used as the macromolecular scaffold, and DFO molecules were bound to the terminals of the PEG branches via amide bonds. The conjugates displayed comparable iron binding ability to the free DFO. Furthermore, these macromolecule conjugates could significantly reduce the cytotoxicity of the free DFO, and showed satisfactory iron clearance capability in the iron overloaded macrophage RAW 246.7. The plasma half-life of the 8-arm-PEG-DFO conjugate was about 190 times than that of DFO when applied to an intravenously administered rat model. In conclusion, research indicated that these star-like PEG-based conjugates could be promising candidates as long circulating, less toxic iron chelators.

scholarly journals Comparison of the Hydroxylase Inhibitor Dimethyloxalylglycine and the Iron Chelator Deferoxamine in Diabetic and Aged Wound Healing

2017 ◽  
Vol 139 (3) ◽  
pp. 695e-706e ◽  
Author(s):  
Dominik Duscher ◽  
Michael Januszyk ◽  
Zeshaan N. Maan ◽  
Alexander J. Whittam ◽  
Michael S. Hu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Iron Chelator ◽  
Iron Chelator Deferoxamine

scholarly journals EFFECT OF IRON OVERLOAD AND IRON CHELATORS ON ANTI-MÜLLERIAN HORMONE LEVEL IN EGYPTIAN FEMALE PATIENTS WITH TRANSFUSION DEPENDENT β-THALASSEMIA

2017 ◽  
Vol 10 (4) ◽  
pp. 263
Author(s):  
Noha Sayed Hamed
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Chelation ◽  
Significant Negative Correlation ◽  
Thalassemia Major ◽  
Iron Chelator ◽  
Female Patients ◽  
Excess Iron ◽  
Thalassemia Minor ◽  
Iron Chelator Deferoxamine

Objective: This work aims to determine the effect of iron overload on serum anti-müllerian hormone (AMH) levels in females subjected to transfusion-dependent β-thalassemia by measuring serum ferritin and to investigate the effects of iron chelation therapy including oral deferiprone and subcutaneous deferoxamine in the management of transfusion-related iron overload together with reproductive function.Methods: 90 female patients with thalassemia major (TM), thalassemia intermedia (TI) and thalassemia minor (T minor) were selected to investigate AMH by ELISA and ferritin by IRMA.Results: Serum AMH level was lower in female patients with transfusion dependent β-thalassemia than in T minor also, Ferritin was 25 fold more in TM compared to T minor (3088.0±2497.6 ng/ml vs. 120.3±36.2 ng/ml). There was significant negative correlation of AMH with ferritin in TM (r =-0.949; P<0.001*), in TI (r =-0.378; P =0.039*) and in T minor (r =-0.754; P<0.001*). The iron chelator, deferoxamine had significantly higher ferritin and lower AMH in TM and TI than deferiprone.Conclusion: the results demonstrated that females with TM and TI were found to have lower serum AMH levels than T minor and inversely related to the serum ferritin levels in all thalassemic groups. Also, it demonstrated that deferiprone was more efficient than deferoxamine in removing excess iron and reduced the deleterious effect of excess iron to the reproductive system, which leads to fertility preservation of female patients with transfusion–dependent β-thalassemia.Keywords: Anti-müllerian hormone, Ferritin, Iron overload, β-thalassemia, Deferoxamine, Deferiprone.

scholarly journals Synergistic inhibition of lymphoid tumor growth in vitro by combined treatment with the iron chelator deferoxamine and an immunoglobulin G monoclonal antibody against the transferrin receptor

Blood ◽  
1990 ◽  
Vol 76 (5) ◽  
pp. 991-995 ◽  
Author(s):  
JD Kemp ◽  
KM Smith ◽  
LJ Kanner ◽  
F Gomez ◽  
JA Thorson ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Immunoglobulin G ◽  
Transferrin Receptor ◽  
Picolinic Acid ◽  
Combined Treatment ◽  
Iron Chelator ◽  
Response Analysis ◽  
Synergistic Inhibition ◽  
Iron Chelator Deferoxamine

Abstract Data are presented indicating that the growth of 5 out of 5 murine lymphoid tumors can be inhibited in a synergistic fashion in vitro by combined treatment with the iron chelator deferoxamine (DFO) and an immunoglobulin G (IgG) monoclonal anti-transferrin receptor antibody (ATRA). A two-way dose/response analysis shows that the ATRA becomes more efficient as an inhibitor with increasing doses of DFO. Flow cytometric studies further support the view that IgG ATRAS impair transferrin receptor (TR) function by causing TR down-modulation and degradation, even when the presence of DFO acts to promote increased cell surface TR expression. It is also shown that an IgG ATRA is nearly as effective as an IgM ATRA in inhibiting tumor cell growth when used in combination with DFO. Finally, studies with the iron chelator picolinic acid show that it produces only additive, or very slightly supra-additive, effects when used in combination with the ATRA. Therefore, these studies not only continue to suggest that combination chelator/ATRA therapy warrants further investigation as a tool in the therapy of hematopoietic malignancies, but also make the following new points: (1) the clinically familiar iron chelator deferoxamine, but not all iron chelators, produces synergistic inhibition of tumor growth in vitro with ATRAS; and (2) IgG ATRAS, which may be clinically more attractive reagents than IgA or IgM ATRAS because of better access to extra vascular tissue spaces, have unexpectedly been found to function as powerful growth inhibitors when used in combination with DFO.

Hydrogen peroxide cytotoxicity in cultured cardiac myocytes is iron dependent

1994 ◽  
Vol 266 (1) ◽  
pp. H121-H127 ◽  
Author(s):  
R. M. Byler ◽  
N. A. Sherman ◽  
J. S. Wallner ◽  
L. D. Horwitz
Keyword(s):  
Hydrogen Peroxide ◽  
Cardiac Myocytes ◽  
Iron Chelator ◽  
Radical Scavenger ◽  
Intracellular Iron ◽  
Trypan Blue Exclusion ◽  
Myocardial Ischemia And Reperfusion ◽  
Reactive Oxygen Metabolite ◽  
Hydroxyl Radical Scavenger ◽  
Iron Chelator Deferoxamine

Because of its potential importance in injury during myocardial ischemia and reperfusion, we assessed mechanisms of hydrogen peroxide (H2O2) cytotoxicity in cultured chick embryo cardiac myocytes. Injury was quantitated by release of lactate dehydrogenase (LDH) or 51Cr, both of which correlated with loss of cell viability assessed by trypan blue exclusion. The iron chelator deferoxamine (0.25–2 mM), but not equimolar iron-loaded deferoxamine, markedly reduced LDH and 51Cr release. Injury was also prevented or attenuated by the diffusible reactive oxygen metabolite scavengers dimethylthiourea (10–20 mM) and N-(2-mercaptopropionyl)-glycine (20 mM). The hydroxyl radical scavenger, dimethyl sulfoxide (200–400 mM), also reduced injury. Other scavengers that probably remained extracellular, superoxide dismutase and mannitol, were ineffective. Thus, with exposure of cardiac myocytes to H2O2, cytotoxicity requires reactions catalyzed by intracellular iron.

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