Superoxide Radicals in the Execution of Cell Death

Fujii, Junichi; Homma, Takujiro; Osaki, Tsukasa

doi:10.3390/antiox11030501

Cited by 136 publications

(88 citation statements)

References 246 publications

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“…The levels of these enzymes were found to be increased in inflammatory cells within the airways of COPD patients [ 83 ]. Although profusely generated superoxide radicals are a comparatively weaker oxidizing agent, however, it is the precursor for various other more detrimental ROS species including hydroxyl radicals, which are increased in the case of COPD, or the highly damaging and strong ONOO − radicals generated by the fast reaction of superoxide with nitric oxide [ 3 , 84 , 85 ]. In a similar manner, myeloperoxidase (MPO), secreted by activated neutrophils, is likely to build up in the lungs of COPD patients, which can further result in the generation of highly damaging HOCl.…”

Section: Sources Of Reactive Oxygen Species In the Lungmentioning

confidence: 99%

Therapeutic Potential of Small Molecules Targeting Oxidative Stress in the Treatment of Chronic Obstructive Pulmonary Disease (COPD): A Comprehensive Review

Dailah

2022

Molecules

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Chronic obstructive pulmonary disease (COPD) is an increasing and major global health problem. COPD is also the third leading cause of death worldwide. Oxidative stress (OS) takes place when various reactive species and free radicals swamp the availability of antioxidants. Reactive nitrogen species, reactive oxygen species (ROS), and their counterpart antioxidants are important for host defense and physiological signaling pathways, and the development and progression of inflammation. During the disturbance of their normal steady states, imbalances between antioxidants and oxidants might induce pathological mechanisms that can further result in many non-respiratory and respiratory diseases including COPD. ROS might be either endogenously produced in response to various infectious pathogens including fungi, viruses, or bacteria, or exogenously generated from several inhaled particulate or gaseous agents including some occupational dust, cigarette smoke (CS), and air pollutants. Therefore, targeting systemic and local OS with therapeutic agents such as small molecules that can increase endogenous antioxidants or regulate the redox/antioxidants system can be an effective approach in treating COPD. Various thiol-based antioxidants including fudosteine, erdosteine, carbocysteine, and N-acetyl-L-cysteine have the capacity to increase thiol content in the lungs. Many synthetic molecules including inhibitors/blockers of protein carbonylation and lipid peroxidation, catalytic antioxidants including superoxide dismutase mimetics, and spin trapping agents can effectively modulate CS-induced OS and its resulting cellular alterations. Several clinical and pre-clinical studies have demonstrated that these antioxidants have the capacity to decrease OS and affect the expressions of several pro-inflammatory genes and genes that are involved with redox and glutathione biosynthesis. In this article, we have summarized the role of OS in COPD pathogenesis. Furthermore, we have particularly focused on the therapeutic potential of numerous chemicals, particularly antioxidants in the treatment of COPD.

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Section: Sources Of Reactive Oxygen Species In the Lungmentioning

confidence: 99%

Therapeutic Potential of Small Molecules Targeting Oxidative Stress in the Treatment of Chronic Obstructive Pulmonary Disease (COPD): A Comprehensive Review

Dailah

2022

Molecules

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“…Therefore, inhibiting ferroptosis in BMSCs may potentially enhance the survival of BMSCs in oxidative stress. Tocopherol can efficiently suppress ferroptosis by neutralizing radical electrons ( Fujii et al, 2022 ). Tocopherol plays cytoprotective effects in the prevention of ferroptosis against oxidative stress ( Saito, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Tocopherol attenuates the oxidative stress of BMSCs by inhibiting ferroptosis through the PI3k/AKT/mTOR pathway

Lan

Yao

et al. 2022

Front. Bioeng. Biotechnol.

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Oxidative stress can induce bone tissue damage and the occurrence of multiple diseases. As a type of traditional medicine, tocopherol has been reported to have a strong antioxidant effect and contributes to osteogenic differentiation. The purpose of this study was to investigate the protective effect of tocopherol on the oxidative stress of rat bone marrow-derived mesenchymal stem cells (BMSCs) and the underlying mechanisms. By establishing an oxidative stress model in vitro, the cell counting kit-8 (CCK-8), reactive oxygen species (ROS) analysis, Western blot (WB), real-time PCR (RT-PCR), alkaline phosphatase (ALP) staining, and Alizarin Red staining (ARS) evaluated the effects of tocopherol on the cell viability, intracellular ROS levels, and osteogenic differentiation in BMSCs. In addition, ferroptosis-related markers were examined via Western blot, RT-PCR, and Mito-FerroGreen. Eventually, the PI3K/AKT/mTOR signaling pathway was explored. We found that tocopherol significantly maintained the cell viability, reduced intracellular ROS levels, upregulated the levels of anti-oxidative genes, promoted the levels of osteogenic-related proteins, and the mRNA of BMSCs stimulated by H2O2. More importantly, tocopherol inhibited ferroptosis and upregulated the phosphorylation levels of PI3K, AKT, and mTOR of BMSCs upon H2O2 stimulation. In summary, tocopherol protected BMSCs from oxidative stress damage via the inhibition of ferroptosis through the PI3K/AKT/mTOR pathway.

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“…These results suggest that H 2 DCF-DA may be the choice fluorescent probe for detecting intracellular peroxidative activity of exogenous peroxides in bacteria and that intracellular O 2 − may be generated in E. coli cells exposed to exogenous organic hydroperoxides [ 26 ].…”

Section: Resultsmentioning

confidence: 99%

Flow Cytometric Analysis of Oxidative Stress in Escherichia coli B Strains Deficient in Genes of the Antioxidant Defence

Jávega

Herrera

O’Connor

2022

IJMS

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The detection of reactive oxygen species (ROS) and the analysis of oxidative stress are frequent applications of functional flow cytometry. Identifying and quantifying the ROS species generated during oxidative stress are crucial steps for the investigation of molecular mechanisms underlying stress responses. Currently, there is a wide availability of fluorogenic substrates for such purposes, but limitations in their specificity and sensitivity may affect the accuracy of the analysis. The aim of our work was to validate a new experimental model based in different strains of Escherichia coli B deficient in key genes for antioxidant defense, namely oxyR, sodA and sodB. We applied this model to systematically assess issues of specificity in fluorescent probes and the involvement of different ROS in a bacterial model of oxidative stress, as the probes can react with a variety of oxidants and free radical species. Our results confirm the higher sensitivity and specificity of the fluorescent probe mitochondrial peroxy yellow 1 (MitoPY1) for the detection of H2O2, and its very low capacity for organic hydroperoxides, thus extending MitoPY1’s specificity for H2O2 in mammalian cells to a bacterial model. On the contrary, the fluorescent probe 2′,7′-dichlorodihydrofluorescein diacetate (H2DCF-DA) is more sensitive to organic peroxides than to H2O2, confirming the lack of selectivity of H2DCF-DA to H2O2. Treatment with organic peroxides and H2O2 suggests a superoxide-independent oxidation of the fluorescent probe Hydroethidine (HE). We found a positive correlation between the lipophilicity of the peroxides and their toxicity to E. coli, suggesting greater quantitative importance of the peroxidative effects on the bacterial membrane and/or greater efficiency of the protection systems against the intracellular effects of H2O2 than against the membrane oxidative stress induced by organic peroxides. Altogether, our results may aid in preventing or minimizing experimental errors and providing recommendations for the proper design of cytometric studies of oxidative stress, in accordance with current recommendations and guidelines.

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Superoxide Radicals in the Execution of Cell Death

Cited by 136 publications

References 246 publications

Therapeutic Potential of Small Molecules Targeting Oxidative Stress in the Treatment of Chronic Obstructive Pulmonary Disease (COPD): A Comprehensive Review

Therapeutic Potential of Small Molecules Targeting Oxidative Stress in the Treatment of Chronic Obstructive Pulmonary Disease (COPD): A Comprehensive Review

Tocopherol attenuates the oxidative stress of BMSCs by inhibiting ferroptosis through the PI3k/AKT/mTOR pathway

Flow Cytometric Analysis of Oxidative Stress in Escherichia coli B Strains Deficient in Genes of the Antioxidant Defence

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