scholarly journals Modulators of Oxidative Stress: Chemical and Pharmacological Aspects

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 657 ◽  
Author(s):  
Luciano Saso ◽  
Hande Gürer-Orhan ◽  
Višnja Stepanić
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Ros Production ◽  
Oxygen Species ◽  
Antioxidant Proteins

Oxidative stress is represented as an imbalance between reactive oxygen species (ROS) production and the response of antioxidant proteins [...]

scholarly journals The Characterization of TA-289, a Novel Antifungal from Fusarium sp.

2021 ◽  
Author(s):  
◽  
Natelle C H Quek
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Cell Death ◽  
Reactive Oxygen ◽  
Chemical Diversity ◽  
Mitochondrial Morphology ◽  
Ros Production ◽  
Oxygen Species ◽  
Wild Type

<p>Natural products offer vast structural and chemical diversity highly sought after in drug discovery research. Saccharomyces cerevisiae makes an ideal model eukaryotic organism for drug mode-of-action studies owing to ease of growth, sophistication of genetic tools and overall homology to higher eukaryotes. Equisetin and a closely related novel natural product, TA-289, are cytotoxic to fermenting yeast, but seemingly less so when yeast actively respire. Cell cycle analyses by flow cytometry revealed a cell cycle block at S-G2/M phase caused by TA-289; previously described oxidative stress-inducing compounds causing cell cycle delay led to further investigation in the involvement of equisetin and TA-289 in mitochondrial-mediated generation of reactive oxygen species. Chemical genomic profiling involving genome-wide scans of yeast deletion mutant strains for TA-289 sensitivity revealed sensitization of genes involved in the mitochondria, DNA damage repair and oxidative stress responses, consistent with a possible mechanism-of-action at the mitochondrion. Flow cytometric detection of reactive oxygen species (ROS) generation caused by TA-289 suggests that the compound may induce cell death via ROS production. The generation of a mutant strain resistant to TA-289 also displayed resistance to a known oxidant, H2O2, at concentrations that were cytotoxic to wild-type cells. The resistant mutant displayed a higher basal level of ROS production compared to the wild-type parent, indicating that the resistance mutation led to an up-regulation of antioxidant capacity which provides cell survival in the presence of TA-289. Yeast mitochondrial morphology was visualized by confocal light microscopy, where it was observed that cells treated with TA-289 displayed abnormal mitochondria phenotypes, further indicating that the compound is acting primarily at the mitochondrion. Similar effects observed with equisetin treatment suggest that both compounds share the same mechanism, eliciting cell death via ROS production in the mitochondrial respiratory chain.</p>

scholarly journals Comparative Reactive Oxygen Species (ROS) Content among Various Flavored Disposable Vape Bars, including Cool (Iced) Flavored Bars

Toxics ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 235
Author(s):  
Shaiesh Yogeswaran ◽  
Thivanka Muthumalage ◽  
Irfan Rahman
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Health Effects ◽  
Reactive Oxygen ◽  
Ros Production ◽  
Oxygen Species ◽  
Aerosol Generator ◽  
Pulmonary Cells ◽  
Single Puff ◽  
Insight Into

Studies have shown that aerosols generated from flavored e-cigarettes contain Reactive Oxygen Species (ROS), promoting oxidative stress-induced damage within pulmonary cells. Our lab investigated the ROS content of e-cigarette vapor generated from disposable flavored e-cigarettes (vape bars) with and without nicotine. Specifically, we analyzed vape bars belonging to multiple flavor categories (Tobacco, Minty Fruit, Fruity, Minty/Cool (Iced), Desserts, and Drinks/Beverages) manufactured by various vendors and of different nicotine concentrations (0–6.8%). Aerosols from these vape bars were generated via a single puff aerosol generator; these aerosols were then individually bubbled through a fluorogenic solution to semi-quantify ROS generated by these bars in H2O2 equivalents. We compared the ROS levels generated by each vape bar as an indirect determinant of their potential to induce oxidative stress. Our results showed that ROS concentration (μM) within aerosols produced from these vape bars varied significantly among different flavored vape bars and identically flavored vape bars with varying nicotine concentrations. Furthermore, our results suggest that flavoring chemicals and nicotine play a differential role in generating ROS production in vape bar aerosols. Our study provides insight into the differential health effects of flavored vape bars, in particular cool (iced) flavors, and the need for their regulation.

scholarly journals Survival Signaling by C-RAF: Mitochondrial Reactive Oxygen Species and Ca2+ Are Critical Targets

2008 ◽  
Vol 28 (7) ◽  
pp. 2304-2313 ◽  
Author(s):  
Andrey V. Kuznetsov ◽  
Julija Smigelskaite ◽  
Christine Doblander ◽  
Manickam Janakiraman ◽  
Martin Hermann ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Reactive Oxygen ◽  
Ros Production ◽  
Oxygen Species ◽  
Mitochondrial Reactive Oxygen Species ◽  
Mitochondrial Ros ◽  
Survival Signaling ◽  
First Time

ABSTRACT Survival signaling by RAF occurs through largely unknown mechanisms. Here we provide evidence for the first time that RAF controls cell survival by maintaining permissive levels of mitochondrial reactive oxygen species (ROS) and Ca2+. Interleukin-3 (IL-3) withdrawal from 32D cells resulted in ROS production, which was suppressed by activated C-RAF. Oncogenic C-RAF decreased the percentage of apoptotic cells following treatment with staurosporine or the oxidative stress-inducing agent tert-butyl hydroperoxide. However, it was also the case that in parental 32D cells growing in the presence of IL-3, inhibition of RAF signaling resulted in elevated mitochondrial ROS and Ca2+ levels. Cell death is preceded by a ROS-dependent increase in mitochondrial Ca2+, which was absent from cells expressing transforming C-RAF. Prevention of mitochondrial Ca2+ overload after IL-3 deprivation increased cell viability. MEK was essential for the mitochondrial effects of RAF. In summary, our data show that survival control by C-RAF involves controlling ROS production, which otherwise perturbs mitochondrial Ca2+ homeostasis.

scholarly journals Cigarette Smoke Promotes Interleukin-8 Production in Alveolar Macrophages Through the Reactive Oxygen Species/Stromal Interaction Molecule 1/Ca2+ Axis

2021 ◽  
Vol 12 ◽  
Author(s):  
Xianying Zhu ◽  
Yuan Zhan ◽  
Yiya Gu ◽  
Qian Huang ◽  
Ting Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cigarette Smoke ◽  
Alveolar Macrophages ◽  
Critical Role ◽  
Reactive Oxygen ◽  
Ros Production ◽  
Oxygen Species ◽  
Stromal Interaction Molecule 1 ◽  
Copd Patients

Chronic obstructive pulmonary disease (COPD), primarily attributed to cigarette smoke (CS), is characterized by multiple pathophysiological changes, including oxidative stress and inflammation. Stromal interaction molecule 1 (STIM1) is a Ca2+ sensor that regulates Ca2+ entry in different types of cells. The present study aimed to explore the relationship between CS-induced oxidative stress and inflammation, as well as the functional role of STIM1 thereinto. Our results showed that the reactive oxygen species (ROS)/STIM1/Ca2+ axis played a critical role in CS-induced secretion of interleukin (IL)-8 in human alveolar macrophages. Specifically, smokers with COPD (SC) showed higher levels of ROS in the lung tissues compared with healthy non-smokers (HN). STIM1 was upregulated in the lung tissues of COPD patients. The expression of STIM1 was positively associated with ROS levels and negatively correlated with pulmonary function. The expression of STIM1 was also increased in the bronchoalveolar lavage fluid (BALF) macrophages of COPD patients and PMA-differentiated THP-1 macrophages stimulated by cigarette smoke extract (CSE). Additionally, CSE-induced upregulation of STIM1 in PMA-differentiated THP-1 macrophages was inhibited by pretreatment with N-acetylcysteine (NAC), a ROS scavenger. Transfection with small interfering RNA (siRNA) targeting STIM1 and pretreatment with NAC alleviated CSE-induced increase in intracellular Ca2+ levels and IL-8 expression. Furthermore, pretreatment with SKF-96365 and 2-APB, the inhibitors of Ca2+ influx, suppressed CSE-induced secretion of IL-8. In conclusion, our study demonstrates that CSE-induced ROS production may increase the expression of STIM1 in macrophages, which further promotes the release of IL-8 by regulating Ca2+ entry. These data suggest that STIM1 may play a crucial role in CSE-induced ROS production and inflammation, and participate in the pathogenesis of COPD.

scholarly journals Extracellular Reactive Oxygen Species (ROS) Production in Fresh Donkey Sperm Exposed to Reductive Stress, Oxidative Stress and NETosis

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1367
Author(s):  
Iván Yánez-Ortiz ◽  
Jaime Catalán ◽  
Yentel Mateo-Otero ◽  
Marta Dordas-Perpinyà ◽  
Sabrina Gacem ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Selection Process ◽  
Reactive Oxygen ◽  
Polymorphonuclear Neutrophils ◽  
Ros Production ◽  
Oxygen Species ◽  
Oxidative Stresses ◽  
Stress Oxidative

Jenny shows a large endometrial reaction after semen influx to the uterus with a large amount of polymorphonuclear neutrophils (PMN) migrating into the uterine lumen. PMN act as a sperm selection mechanism through phagocytosis and NETosis (DNA extrudes and, together with proteins, trap spermatozoa). While a reduced percentage of spermatozoa are phagocytosed by PMN, most are found to be attached to neutrophil extracellular traps (NETs). This selection process together with sperm metabolism produces a large amount of reactive oxygen species (ROS) that influence the reproductive success. The present study aimed to determine the extracellular ROS production in both sperm and PMN. With this purpose, (1) donkey sperm were exposed to reductive and oxidative stresses, through adding different concentrations of reduced glutathione (GSH) and hydrogen peroxide (H2O2), respectively; and (2) PMN were subjected to NETosis in the presence of the whole semen, sperm, seminal plasma (SP) or other activators such as formyl-methionyl-leucyl-phenylalanine (FMLP). Extracellular ROS production (measured as H2O2 levels) was determined with the Amplex® Red Hydrogen Peroxide/Peroxidase Assay Kit. Donkey sperm showed more resilience to oxidative stress than to the reductive one, and GSH treatments led to greater H2O2 extracellular production. Moreover, not only did SP appear to be the main inducer of NETosis in PMN, but it was also able to maintain the extracellular H2O2 levels produced by sperm and NETosis.

scholarly journals The Characterization of TA-289, a Novel Antifungal from Fusarium sp.

2021 ◽  
Author(s):  
◽  
Natelle C H Quek
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Cell Death ◽  
Reactive Oxygen ◽  
Chemical Diversity ◽  
Mitochondrial Morphology ◽  
Ros Production ◽  
Oxygen Species ◽  
Wild Type

<p>Natural products offer vast structural and chemical diversity highly sought after in drug discovery research. Saccharomyces cerevisiae makes an ideal model eukaryotic organism for drug mode-of-action studies owing to ease of growth, sophistication of genetic tools and overall homology to higher eukaryotes. Equisetin and a closely related novel natural product, TA-289, are cytotoxic to fermenting yeast, but seemingly less so when yeast actively respire. Cell cycle analyses by flow cytometry revealed a cell cycle block at S-G2/M phase caused by TA-289; previously described oxidative stress-inducing compounds causing cell cycle delay led to further investigation in the involvement of equisetin and TA-289 in mitochondrial-mediated generation of reactive oxygen species. Chemical genomic profiling involving genome-wide scans of yeast deletion mutant strains for TA-289 sensitivity revealed sensitization of genes involved in the mitochondria, DNA damage repair and oxidative stress responses, consistent with a possible mechanism-of-action at the mitochondrion. Flow cytometric detection of reactive oxygen species (ROS) generation caused by TA-289 suggests that the compound may induce cell death via ROS production. The generation of a mutant strain resistant to TA-289 also displayed resistance to a known oxidant, H2O2, at concentrations that were cytotoxic to wild-type cells. The resistant mutant displayed a higher basal level of ROS production compared to the wild-type parent, indicating that the resistance mutation led to an up-regulation of antioxidant capacity which provides cell survival in the presence of TA-289. Yeast mitochondrial morphology was visualized by confocal light microscopy, where it was observed that cells treated with TA-289 displayed abnormal mitochondria phenotypes, further indicating that the compound is acting primarily at the mitochondrion. Similar effects observed with equisetin treatment suggest that both compounds share the same mechanism, eliciting cell death via ROS production in the mitochondrial respiratory chain.</p>

scholarly journals Oxidative Stress Induced by Reactive Oxygen Species (ROS) and NADPH Oxidase 4 (NOX4) in the Pathogenesis of the Fibrotic Process in Systemic Sclerosis: A Promising Therapeutic Target

2021 ◽  
Vol 10 (20) ◽  
pp. 4791
Author(s):  
Sonsoles Piera-Velazquez ◽  
Sergio A. Jimenez
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Systemic Sclerosis ◽  
Nadph Oxidase ◽  
Therapeutic Target ◽  
Reactive Oxygen ◽  
Dermal Fibroblasts ◽  
Ros Production ◽  
Oxygen Species ◽  
Fibrotic Process

Numerous clinical and research investigations conducted during the last two decades have implicated excessive oxidative stress caused by high levels of reactive oxygen species (ROS) in the development of the severe and frequently progressive fibrotic process in Systemic Sclerosis (SSc). The role of excessive oxidative stress in SSc pathogenesis has been supported by the demonstration of increased levels of numerous biomarkers, indicative of cellular and molecular oxidative damage in serum, plasma, and other biological fluids from SSc patients, and by the demonstration of elevated production of ROS by various cell types involved in the SSc fibrotic process. However, the precise mechanisms mediating oxidative stress development in SSc and its pathogenetic effects have not been fully elucidated. The participation of the NADPH oxidase NOX4, has been suggested and experimentally supported by the demonstration that SSc dermal fibroblasts display constitutively increased NOX4 expression and that reduction or abrogation of NOX4 effects decreased ROS production and the expression of genes encoding fibrotic proteins. Furthermore, NOX4-stimulated ROS production may be involved in the development of certain endothelial and vascular abnormalities and may even participate in the generation of SSc-specific autoantibodies. Collectively, these observations suggest NOX4 as a novel therapeutic target for SSc.

scholarly journals IκB kinase promotes Nrf2 ubiquitination and degradation by phosphorylating cylindromatosis, aggravating oxidative stress injury in obesity-related nephropathy

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Yin-Yin Chen ◽  
Han Hong ◽  
Yu-Ting Lei ◽  
Jia Zou ◽  
Yi-Ya Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Related Factor ◽  
Ros Production ◽  
Oxygen Species ◽  
Stress Injury ◽  
Oxidative Stress Injury ◽  
Iκb Kinase

Abstract Background Obesity-related nephropathy (ORN) has become one of the leading causes of end-stage renal disease and has tripled over the past decade. Previous studies have demonstrated that decreased reactive oxygen species production may contribute to improving ORN by ameliorating oxidative stress injury. Here, IκB kinase (IKK) was hypothesized to inactivate the deubiquitination activity of cylindromatosis (CYLD) by activating the phosphorylation of CYLD, thus promoting the ubiquitination of NF-E2-related factor 2 (Nrf2) and further aggravating oxidative stress injury of the kidney in ORN. This study was aimed to confirm this hypothesis. Methods Haematoxylin and eosin (HE), periodic acid-Schiff (PAS) and Oil Red O staining were performed to assess histopathology. Dihydroethidium (DHE) staining and MDA, SOD, CAT, and GSH-PX assessments were performed to measure reactive oxygen species (ROS) production. Immunohistochemical (IHC) staining, qRT–PCR and/or western blotting were performed to assess the expression of related genes. JC-1 assays were used to measure the mitochondrial membrane potential (ΔΨm) of treated HK-2 cells. Co-immunoprecipitation experiments (Co-IP) were used to analyse the interaction between CYLD and Nrf2 in ORN. Results ORN in vivo and in vitro models were successfully constructed, and oxidative stress injury was detected in the model tissues and cells. Compared with the control groups, the phosphorylation level of CYLD increased while Nrf2 levels decreased in ORN model cells. An IKK inhibitor reduced lipid deposition, ROS production, CYLD phosphorylation levels and ΔΨm in vitro, which were reversed by knockdown of CYLD. Nrf2 directly bound to CYLD and was ubiquitinated in ORN cells. The proteasome inhibitor MG132 activated the Nrf2/ARE signalling pathway, thereby reversing the promoting effect of CYLD knockdown on oxidative stress. Conclusion IKK inactivates the deubiquitination activity of CYLD by activating the phosphorylation of CYLD, thus promoting the ubiquitination of Nrf2 and further aggravating oxidative stress injury of the kidney in ORN. This observation provided a feasible basis for the treatment of kidney damage caused by ORN.

scholarly journals A Quantitative Method to Monitor Reactive Oxygen Species Production by Electron Paramagnetic Resonance in Physiological and Pathological Conditions

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Simona Mrakic-Sposta ◽  
Maristella Gussoni ◽  
Michela Montorsi ◽  
Simone Porcelli ◽  
Alessandra Vezzoli
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Electron Paramagnetic Resonance ◽  
Venous Blood ◽  
Reactive Oxygen ◽  
Capillary Blood ◽  
Ros Production ◽  
Oxygen Species ◽  
Paramagnetic Resonance ◽  
Electron Paramagnetic

The growing interest in the role of Reactive Oxygen Species (ROS) and in the assessment of oxidative stress in health and disease clashes with the lack of consensus on reliable quantitative noninvasive methods applicable. The study aimed at demonstrating that a recently developed Electron Paramagnetic Resonance microinvasive method provides direct evidence of the “instantaneous” presence of ROS returning absolute concentration levels that correlate with “a posteriori” assays of ROS-induced damage by means of biomarkers. The reliability of the choice to measure ROS production rate in human capillary blood rather than in plasma was tested (step I). A significant (P<0.01) linear relationship between EPR data collected on capillary blood versus venous blood (R2=0.95), plasma (R2=0.82), and erythrocytes (R2=0.73) was found. Then (step II) ROS production changes of various subjects’ categories, young versus old and healthy versus pathological at rest condition, were found significantly different (range 0.0001–0.05Plevel). The comparison of the results with antioxidant capacity and oxidative damage biomarkers concentrations showed that all changes indicating increased oxidative stress are directly related to ROS production increase. Therefore, the adopted method may be an automated technique for a lot of routine in clinical trials.

scholarly journals The Differential Reactive Oxygen Species Production of Tear Neutrophils in Response to Various Stimuli In Vitro

2021 ◽  
Vol 22 (23) ◽  
pp. 12899
Author(s):  
Yutong Jin ◽  
Brian Dixon ◽  
Lyndon Jones ◽  
Maud Gorbet
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Reactive Oxygen ◽  
Magnetic Bead ◽  
Polymorphonuclear Neutrophils ◽  
Ros Generation ◽  
Ros Production ◽  
Oxygen Species ◽  
High Level

A large number of polymorphonuclear neutrophils (PMNs) invade the ocular surface during prolonged eye closure (sleep); these leukocytes are commonly referred as tear PMNs. PMNs contribute to homeostasis and possess an arsenal of inflammatory mediators to protect against pathogens and foreign materials. This study examined the ability of tear PMNs to generate reactive oxygen species (ROS), an essential killing mechanism for PMNs which can lead to oxidative stress and imbalance. Cells were collected after sleep from healthy participants using a gentle eye wash. ROS production in stimulated (phorbol-12-myristate-13-acetate (PMA), lipopolysaccharides (LPS) or N-Formylmethionyl-leucyl-phenylalanine (fMLP)) and unstimulated tear PMNs was measured using luminol-enhanced chemiluminescence for 60 min. A high level of constitutive/spontaneous ROS production was observed in tear PMNs in the absence of any stimulus. While tear PMNs were able to produce ROS in response to PMA, they failed to appropriately respond to LPS and fMLP, although fMLP-stimulated tear PMNs generated ROS extracellularly in the first three minutes. Higher ROS generation was observed in isolated tear PMNs which may be due to priming from the magnetic bead cell separation system. The differential responses of tear PMNs in ROS generation provide further evidence of their potential inflammatory roles in ocular complications involving oxidative stress.

Sign in / Sign up

Export Citation Format

Share Document