scholarly journals Hydroxyl radical is produced via the Fenton reaction in submitochondrial particles under oxidative stress: implications for diseases associated with iron accumulation

Redox Report ◽  
2009 ◽  
Vol 14 (3) ◽  
pp. 102-108 ◽  
Author(s):  
Carin Thomas ◽  
Melissa M. Mackey ◽  
Amy A. Diaz ◽  
David P. Cox
Keyword(s):  
Oxidative Stress ◽  
Hydroxyl Radical ◽  
Fenton Reaction ◽  
Iron Accumulation ◽  
Submitochondrial Particles

Induction of Gamma-Glutamyltransferase Activity and Consequent Pro-oxidant Reactions in Human Macrophages Exposed to Crocidolite Asbestos

2019 ◽  
Vol 177 (2) ◽  
pp. 476-482 ◽  
Author(s):  
Alessandro Corti ◽  
Justine Bonetti ◽  
Silvia Dominici ◽  
Simona Piaggi ◽  
Vanna Fierabracci ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydroxyl Radical ◽  
Fenton Reaction ◽  
Redox Cycling ◽  
Pathogenic Potential ◽  
Gamma Glutamyltransferase ◽  
Reduction Of Iron ◽  
Healthy Donors ◽  
Iron Redox

Abstract Asbestos is the main causative agent of malignant pleural mesothelioma. The variety known as crocidolite (blue asbestos) owns the highest pathogenic potential, due to the dimensions of its fibers as well as to its content of iron. The latter can in fact react with macrophage-derived hydrogen peroxide in the so called Fenton reaction, giving rise to highly reactive and mutagenic hydroxyl radical. On the other hand, hydroxyl radical can as well originate after thiol-dependent reduction of iron, a process capable of starting its redox cycling. Previous studies showed that glutathione (GSH) is one such thiol, and that cellular gamma-glutamyltransferase (GGT) can efficiently potentiate GSH-dependent iron redox cycling and consequent oxidative stress. As GGT is expressed in macrophages and is released upon their activation, the present study was aimed at verifying the hypothesis that GSH/GGT-dependent redox reactions may participate in the oxidative stress following the activation of macrophages induced by crocidolite asbestos. Experiments in acellular systems confirmed that GGT-mediated metabolism of GSH can potentiate crocidolite-dependent production of superoxide anion, through the production of highly reactive dipeptide thiol cysteinyl-glycine. Cultured THP-1 macrophagic cells, as well as isolated monocytes obtained from healthy donors and differentiated to macrophages in vitro, were investigated as to their expression of GGT and the effects of exposure to crocidolite. The results show that crocidolite asbestos at subtoxic concentrations (50–250 ng/1000 cells) can upregulate GGT expression, which raises the possibility that macrophage-initiated, GSH/GGT-dependent pro-oxidant reactions may participate in the pathogenesis of tissue damage and inflammation consequent to crocidolite intoxication.

scholarly journals Contribution of Oxidative Damage to Antimicrobial Lethality

2009 ◽  
Vol 53 (4) ◽  
pp. 1395-1402 ◽  
Author(s):  
Xiuhong Wang ◽  
Xilin Zhao
Keyword(s):  
Oxidative Stress ◽  
Escherichia Coli ◽  
Hydroxyl Radical ◽  
Hydroxyl Radicals ◽  
Fenton Reaction ◽  
Iron Chelator ◽  
Radical Scavenger ◽  
Alkyl Hydroperoxide ◽  
Hydroxyl Radical Scavenger ◽  
Rapid Conversion

ABSTRACT A potential pathway linking hydroxyl radicals to antimicrobial lethality was examined by using mutational and chemical perturbations of Escherichia coli. Deficiencies of sodA or sodB had no effect on norfloxacin lethality; however, the absence of both genes together reduced lethal activity, consistent with rapid conversion of excessive superoxide to hydrogen peroxide contributing to quinolone lethality. Norfloxacin was more lethal with a mutant deficient in katG than with its isogenic parent, suggesting that detoxification of peroxide to water normally reduces quinolone lethality. An iron chelator (bipyridyl) and a hydroxyl radical scavenger (thiourea) reduced the lethal activity of norfloxacin, indicating that norfloxacin-stimulated accumulation of peroxide affects lethal activity via hydroxyl radicals generated through the Fenton reaction. Ampicillin and kanamycin, antibacterials unrelated to fluoroquinolones, displayed behavior similar to that of norfloxacin except that these two agents showed hyperlethality with an ahpC (alkyl hydroperoxide reductase) mutant rather than with a katG mutant. Collectively, these data are consistent with antimicrobial stress increasing the production of superoxide, which then undergoes dismutation to peroxide, from which a highly toxic hydroxyl radical is generated. Hydroxyl radicals then enhance antimicrobial lethality, as suggested by earlier work. Such findings indicate that oxidative stress networks may provide targets for antimicrobial potentiation.

A Systematic DFT Study of Two Elementary Steps Involving Hydrogen Peroxide and the Hydroxyl Radical in the Fenton Reaction

2018 ◽  
Author(s):  
Danilo Carmona ◽  
David Contreras ◽  
Oscar A. Douglas-Gallardo ◽  
Stefan Vogt-Geisse ◽  
Pablo Jaque ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Hydroxyl Radical ◽  
Ab Initio ◽  
Fenton Reaction ◽  
Basis Set ◽  
Basis Sets ◽  
Dft Methods ◽  
Elementary Steps ◽  
Oxygen Oxygen ◽  
Complete Basis Set

The Fenton reaction plays a central role in many chemical and biological processes and has various applications as e.g. water remediation. The reaction consists of the iron-catalyzed homolytic cleavage of the oxygen-oxygen bond in the hydrogen peroxide molecule and the reduction of the hydroxyl radical. Here, we study these two elementary steps with high-level ab-initio calculations at the complete basis set limit and address the performance of different DFT methods following a specific classification based on the Jacob´s ladder in combination with various Pople's basis sets. Ab-initio calculations at the complete basis set limit are in agreement to experimental reference data and identified a significant contribution of the electron correlation energy to the bond dissociation energy (BDE) of the oxygen-oxygen bond in hydrogen peroxide and the electron affinity (EA) of the hydroxyl radical. The studied DFT methods were able to reproduce the ab-initio reference values, although no functional was particularly better for both reactions. The inclusion of HF exchange in the DFT functionals lead in most cases to larger deviations, which might be related to the poor description of the two reactions by the HF method. Considering the computational cost, DFT methods provide better BDE and EA values than HF and post--HF methods with an almost MP2 or CCSD level of accuracy. However, no systematic general prediction of the error based on the employed functional could be established and no systematic improvement with increasing the size in the Pople's basis set was found, although for BDE values certain systematic basis set dependence was observed. Moreover, the quality of the hydrogen peroxide, hydroxyl radical and hydroxyl anion structures obtained from these functionals was compared to experimental reference data. In general, bond lengths were well reproduced and the error in the angles were between one and two degrees with some systematic trend with the basis sets. From our results we conclude that DFT methods present a computationally less expensive alternative to describe the two elementary steps of the Fenton reaction. However, choice of approximated functionals and basis sets must be carefully done and the provided benchmark allows a systematic validation of the electronic structure method to be employed

A Novel pH-responsive Fe-MOF System for Enhanced Cancer Treatment Mediated by Fenton Reaction

2021 ◽  
Author(s):  
Senlin Wang ◽  
Hong-Shuai Wu ◽  
Kai Sun ◽  
Jinzhong Hu ◽  
Fanghui Chen ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Hydroxyl Radical ◽  
Cancer Treatment ◽  
Cell Apoptosis ◽  
Fenton Reaction ◽  
Reactive Oxygen ◽  
Cationic Polymer ◽  
Intracellular Reactive Oxygen Species ◽  
Oxygen Species ◽  
Ph Responsive

Recently, the toxic hydroxyl radical (·OH) has received wide interest in inducing cell apoptosis by increasing the intracellular reactive oxygen species (ROS) levels. Herein, a cationic polymer (MV-PAH) was rationally...

scholarly journals Treatment of the Fluoroquinolone-Associated Disability: The Pathobiochemical Implications

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Krzysztof Michalak ◽  
Aleksandra Sobolewska-Włodarczyk ◽  
Marcin Włodarczyk ◽  
Justyna Sobolewska ◽  
Piotr Woźniak ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Enzyme Activity ◽  
Antibiotic Therapy ◽  
Effective Treatment ◽  
Social Problem ◽  
Fenton Reaction ◽  
Current Paper ◽  
Bivalent Cations

Long-term fluoroquinolone-associated disability (FQAD) after fluoroquinolone (FQ) antibiotic therapy appears in recent years as a significant medical and social problem, because patients suffer for many years after prescribed antimicrobial FQ treatment from tiredness, concentration problems, neuropathies, tendinopathies, and other symptoms. The knowledge about the molecular activity of FQs in the cells remains unclear in many details. The effective treatment of this chronic state remains difficult and not effective. The current paper reviews the pathobiochemical properties of FQs, hints the directions for further research, and reviews the research concerning the proposed treatment of patients. Based on the analysis of literature, the main directions of possible effective treatment of FQAD are proposed: (a) reduction of the oxidative stress, (b) restoring reduced mitochondrion potential ΔΨm, (c) supplementation of uni- and bivalent cations that are chelated by FQs and probably ineffectively transported to the cell (caution must be paid to Fe and Cu because they may generate Fenton reaction), (d) stimulating the mitochondrial proliferation, (e) removing FQs permanently accumulated in the cells (if this phenomenon takes place), and (f) regulating the disturbed gene expression and enzyme activity.

scholarly journals Branched‐chain amino acids reduce hepatic iron accumulation and oxidative stress in hepatitis C virus polyprotein‐expressing mice

2014 ◽  
Vol 35 (4) ◽  
pp. 1303-1314 ◽  
Author(s):  
Masaaki Korenaga ◽  
Sohji Nishina ◽  
Keiko Korenaga ◽  
Yasuyuki Tomiyama ◽  
Naoko Yoshioka ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Amino Acids ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Branched Chain Amino Acids ◽  
Iron Accumulation ◽  
Hepatic Iron ◽  
Branched Chain ◽  
Virus Polyprotein ◽  
And Oxidative Stress

Fenton-like reaction of iron(II)-histidine complex generates hydroxyl radical: implications for oxidative stress and Alzheimer's disease

2021 ◽  
Author(s):  
Can Wang ◽  
Zheng Wang ◽  
Binglin Zeng ◽  
Meiqing Zheng ◽  
Nao Xiao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Hydroxyl Radical ◽  
Common Understanding

The hydroxyl radical (•OH), generated from Fenton/Fenton-like reactions of iron(II) species in biology, can oxidatively damage biomolecules, inducing oxidative stress and diseases. However, this common understanding has been questioned recently...

scholarly journals Involvement of a local Fenton reaction in the reciprocal modulation by O2 of the glucagon-dependent activation of the phosphoenolpyruvate carboxykinase gene and the insulin-dependent activation of the glucokinase gene in rat hepatocytes

1998 ◽  
Vol 335 (2) ◽  
pp. 425-432 ◽  
Author(s):  
Thomas KIETZMANN ◽  
Torsten PORWOL ◽  
Karl ZIEROLD ◽  
Kurt JUNGERMANN ◽  
Helmut ACKER
Keyword(s):  
Hydroxyl Radical ◽  
Hydroxyl Radicals ◽  
Fenton Reaction ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Gene Activation ◽  
Three Dimensional ◽  
Rat Hepatocytes ◽  
Confocal Laser ◽  
Radical Scavenger ◽  
Insulin Dependent

H2O2 mimicked the action of periportal pO2 in the modulation by O2 of the glucagon-dependent activation of the phosphoenolpyruvate carboxykinase (PCK) gene and the insulin-dependent activation of the glucokinase (GK) gene. H2O2 can be converted in the presence of Fe2+ in a Fenton reaction into hydroxyl anions and hydroxyl radicals (•OH). The hydroxyl radicals are highly reactive and might interfere locally with transcription factors. It was the aim of the present study to investigate the role of and to localize such a Fenton reaction. Hepatocytes cultured for 24 h were treated under conditions mimicking periportal or perivenous pO2 with glucagon or insulin plus the iron chelator desferrioxamine (DSF) or the hydroxyl radical scavenger dimethylthiourea (DMTU) to inhibit the Fenton reaction. PCK mRNA was induced by glucagon maximally under conditions of periportal pO2 and half-maximally under venous pO2. GK mRNA was induced by insulin with reciprocal modulation by O2. DSF and DMTU reduced the induction of PCK mRNA to about half-maximal and increased the induction of GK mRNA to maximal under both O2 tensions. Hydroxyl radical formation was maximal under arterial pO2. Perivenous pO2, DSF and DMTU each decreased the formation of •OH to about 70% of control. The Fenton reaction could be localized in a perinuclear space by confocal laser microscopy and three-dimensional reconstruction techniques. In the same compartment, iron could be detected by electron-probe X-ray microanalysis. Thus a local Fenton reaction is involved in the O2 signalling, which modulated the glucagon- and insulin-dependent PCK gene and GK gene activation.

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