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Environmental Science & Technology Nov 2023Water quality and its impacts on human and ecosystem health presents tremendous global challenges. While oxidative water treatment can solve many of these problems... (Review)
Review
Water quality and its impacts on human and ecosystem health presents tremendous global challenges. While oxidative water treatment can solve many of these problems related to hygiene and micropollutants, identifying and predicting transformation products from a large variety of micropollutants induced by dosed chemical oxidants and in situ formed radicals is still a major challenge. To this end, a better understanding of the formed transformation products and their potential toxicity is needed. Currently, no theoretical tools alone can predict oxidatively induced transformation products in aqueous systems. Coupling experimental and theoretical studies has advanced the understanding of reaction kinetics and mechanisms significantly. This perspective article highlights the key progress made concerning experimental and computational approaches to predict transformation products. Knowledge gaps are identified, and the research required to advance the predictive capability is discussed.
Topics: Humans; Ecosystem; Water Pollutants, Chemical; Oxidation-Reduction; Oxidants; Models, Theoretical; Kinetics
PubMed: 37824098
DOI: 10.1021/acs.est.3c04086 -
Proceedings of the National Academy of... Dec 2023Natural products that possess antibiotic and antitumor qualities are often suspected of working through oxidative mechanisms. In this study, two quinone-based small...
Natural products that possess antibiotic and antitumor qualities are often suspected of working through oxidative mechanisms. In this study, two quinone-based small molecules were compared. Menadione, a classic redox-cycling compound, was confirmed to generate high levels of reactive oxygen species inside . It inactivated iron-cofactored enzymes and blocked growth. However, despite the substantial levels of oxidants that it produced, it was unable to generate significant DNA damage and was not lethal. Streptonigrin, in contrast, was poorer at redox cycling and did not inactivate enzymes or block growth; however, even in low doses, it damaged DNA and killed cells. Its activity required iron and oxygen, and in vitro experiments indicated that its quinone moiety transferred electrons through the adjacent iron atom to oxygen. Additionally, in vitro experiments revealed that streptonigrin was able to damage DNA without inhibition by catalase, indicating that hydrogen peroxide was not involved. We infer that streptonigrin can reduce bound oxygen directly to a ferryl species, which then oxidizes the adjacent DNA, without release of superoxide or hydrogen peroxide intermediates. This scheme allows streptonigrin to kill a bacterial cell without interference by scavenging enzymes. Moreover, its minimal redox-cycling behavior avoids alerting either the OxyR or the SoxRS systems, which otherwise would block killing. This example highlights qualities that may be important in the design of oxidative drugs. These results also cast doubt on proposals that bacteria can be killed by stressors that merely stimulate intracellular O and HO formation.
Topics: Oxidants; Hydrogen Peroxide; Anti-Bacterial Agents; Streptonigrin; Oxidative Stress; Escherichia coli; Oxygen; Iron; DNA; Quinones
PubMed: 38109539
DOI: 10.1073/pnas.2312110120 -
Cell Reports Nov 2023Vascular endothelial growth factor receptor-2 (VEGFR2) plays a key role in maintaining vascular endothelial homeostasis. Here, we show that blood flows determine...
Vascular endothelial growth factor receptor-2 (VEGFR2) plays a key role in maintaining vascular endothelial homeostasis. Here, we show that blood flows determine activation and inactivation of VEGFR2 through selective cysteine modifications. VEGFR2 activation is regulated by reversible oxidation at Cys residue. HO-mediated VEGFR2 oxidation is induced by oscillatory flow in vascular endothelial cells through the induction of NADPH oxidase-4 expression. In contrast, laminar flow induces the expression of endothelial nitric oxide synthase and results in the S-nitrosylation of VEGFR2 at Cys, which counteracts the oxidative inactivation. The shear stress model study reveals that disturbed blood flow operated by partial ligation in the carotid arteries induces endothelial damage and intimal hyperplasia in control mice but not in knock-in mice harboring the oxidation-resistant mutant (C1206S) of VEGFR2. Thus, our findings reveal that flow-dependent redox regulation of the VEGFR2 kinase is critical for the structural and functional integrity of the arterial endothelium.
Topics: Animals; Mice; Endothelial Cells; Endothelium, Vascular; Hydrogen Peroxide; Oxidation-Reduction; Signal Transduction; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2
PubMed: 37910508
DOI: 10.1016/j.celrep.2023.113361 -
Journal of Thrombosis and Haemostasis :... Aug 2023Oxidative stress contributes to thrombosis in atherosclerosis, inflammation, infection, aging, and malignancy. Oxidant-induced cysteine modifications, including...
BACKGROUND
Oxidative stress contributes to thrombosis in atherosclerosis, inflammation, infection, aging, and malignancy. Oxidant-induced cysteine modifications, including sulfenylation, can act as a redox-sensitive switch that controls protein function. Protein disulfide isomerase (PDI) is a prothrombotic enzyme with exquisitely redox-sensitive active-site cysteines.
OBJECTIVES
We hypothesized that PDI is sulfenylated during oxidative stress, contributing to the prothrombotic potential of PDI.
METHODS
Biochemical and enzymatic assays using purified proteins, platelet and endothelial cell assays, and in vivo murine thrombosis studies were used to evaluate the role of oxidative stress in PDI sulfenylation and prothrombotic activity.
RESULTS
PDI exposure to oxidants resulted in the loss of PDI reductase activity and simultaneously promoted sulfenylated PDI generation. Following exposure to oxidants, sulfenylated PDI spontaneously converted to disulfided PDI. PDI oxidized in this manner was able to transfer disulfides to protein substrates. Inhibition of sulfenylation impaired disulfide formation by oxidants, indicating that sulfenylation is an intermediate during PDI oxidation. Agonist-induced activation of platelets and endothelium resulted in the release of sulfenylated PDI. PDI was also sulfenylated by oxidized low-density lipoprotein (oxLDL). In an in vivo model of thrombus formation, oxLDL markedly promoted platelet accumulation following an arteriolar injury. PDI oxidoreductase inhibition blocked oxLDL-mediated augmentation of thrombosis.
CONCLUSION
PDI sulfenylation is a critical posttranslational modification that is an intermediate during disulfide PDI formation in the setting of oxidative stress. Oxidants generated by vascular cells during activation promote PDI sulfenylation, and interference with PDI during oxidative stress impairs thrombus formation.
Topics: Animals; Mice; Cysteine; Disulfides; Oxidants; Oxidative Stress; Oxidoreductases; Protein Disulfide-Isomerases; Thrombosis
PubMed: 37037379
DOI: 10.1016/j.jtha.2023.03.034 -
Neurologia Apr 2024This paper highlights the relationship of inflammation and oxidative stress as damage mechanisms of Multiple Sclerosis (MS), considered an inflammatory and autoimmune... (Review)
Review
INTRODUCTION
This paper highlights the relationship of inflammation and oxidative stress as damage mechanisms of Multiple Sclerosis (MS), considered an inflammatory and autoimmune disease.
DEVELOPMENT
The oxidative stress concept has been defined by an imbalance between oxidants and antioxidants in favor of the oxidants. There is necessary to do physiological functions, like the respiration chain, but in certain conditions, the production of reactive species overpassed the antioxidant systems, which could cause tissue damage. On the other hand, it is well established that inflammation is a complex reaction in the vascularized connective tissue in response to diverse stimuli. However, an unregulated prolonged inflammatory process also can induce tissue damage.
CONCLUSION
Both inflammation and oxidative stress are interrelated since one could promote the other, leading to a toxic feedback system, which contributes to the inflammatory and demyelination process in MS.
Topics: Humans; Multiple Sclerosis; Oxidative Stress; Inflammation; Antioxidants; Oxidants
PubMed: 38553104
DOI: 10.1016/j.nrleng.2021.10.010 -
Chemosphere Oct 2023Nitrogen oxides (NO = NO + NO) are important atmospheric pollutants that are directly harmful to human health. Recently in urban and industrial areas, synthetic...
Nitrogen oxides (NO = NO + NO) are important atmospheric pollutants that are directly harmful to human health. Recently in urban and industrial areas, synthetic materials have been developed and deployed to photocatalytically oxidize NO to nitrate (NO) in order to improve air quality. We show that the natural presence of small amounts (≤5%) of titanium oxides, such as anatase and rutile, can also drive NO oxidation to nitrate in soils under UV-visible irradiation. The NO uptake coefficients ranged between 0.1 × 10 for sandy soils to 6.4 × 10 in the case of tropical clay soils; the latter comparable in efficiency to current industrial man-made catalysts. This photocatalytic N-fixation mechanism offers a new strategy for NO mitigation from the atmosphere by transforming it into nitrate, and simultaneously provides an energy efficient source of essential fertilizer to agriculture.
Topics: Humans; Nitrates; Soil; Nitrogen Oxides; Air Pollution; Ultraviolet Rays
PubMed: 37474039
DOI: 10.1016/j.chemosphere.2023.139576 -
Sensors (Basel, Switzerland) Jun 2023This paper investigates the effect of decorating graphene with zinc oxide (ZnO) nanoparticles (NPs) for the detection of NO. In this regard, two graphene sensors with...
This paper investigates the effect of decorating graphene with zinc oxide (ZnO) nanoparticles (NPs) for the detection of NO. In this regard, two graphene sensors with different ZnO loadings of 5 wt.% and 20 wt.% were prepared, and their responses towards NO at room temperature and different conditions were compared. The experimental results demonstrate that the graphene loaded with 5 wt.% ZnO NPs (G95/5) shows better performance at detecting low concentrations of the target gas than the one loaded with 20 wt.% ZnO NPs (G80/20). Moreover, measurements under dry and humid conditions of the G95/5 sensor revealed that the material is very sensitive to ambient moisture, showing an almost eight-fold increase in NO sensitivity when the background changes from dry to 70% relative humidity. Regarding sensor selectivity, it presents a significant selectivity towards NO compared to other gas compounds.
Topics: Graphite; Nitrogen Dioxide; Zinc Oxide; Nanoparticles
PubMed: 37447904
DOI: 10.3390/s23136055 -
Biogerontology Oct 2023L-lactate is a catabolite from the anaerobic metabolism of glucose, which plays a paramount role as a signaling molecule in various steps of the cell survival. Its... (Review)
Review
L-lactate is a catabolite from the anaerobic metabolism of glucose, which plays a paramount role as a signaling molecule in various steps of the cell survival. Its activity, as a master tuner of many mechanisms underlying the aging process, for example in the skin, is still presumptive, however its crucial position in the complex cross-talk between mitochondria and the process of cell survival, should suggest that L-lactate may be not a simple waste product but a fine regulator of the aging/survival machinery, probably via mito-hormesis. Actually, emerging evidence is highlighting that ROS are crucial in the signaling of skin health, including mechanisms underlying wound repair, renewal and aging. The ROS, including superoxide anion, hydrogen peroxide, and nitric oxide, play both beneficial and detrimental roles depending upon their levels and cellular microenvironment. Physiological ROS levels are essential for cutaneous health and the wound repair process. Aberrant redox signaling activity drives chronic skin disease in elderly. On the contrary, impaired redox modulation, due to enhanced ROS generation and/or reduced levels of antioxidant defense, suppresses wound healing via promoting lymphatic/vascular endothelial cell apoptosis and death. This review tries to elucidate this issue.
Topics: Humans; Aged; Reactive Oxygen Species; Skin Aging; Superoxides; Oxidation-Reduction; Lactates
PubMed: 36708434
DOI: 10.1007/s10522-023-10018-1 -
Disease Markers 2023Periodontitis is intricately linked to oxidative stress-antioxidant (redox) imbalance. The antioxidant system scavenges the oxygen free radicals in biological fluids in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Periodontitis is intricately linked to oxidative stress-antioxidant (redox) imbalance. The antioxidant system scavenges the oxygen free radicals in biological fluids in patients with periodontitis. However, little is still known about the free radicals mediated oxidative stress and reductive ability of the antioxidant system. Thus, the present meta-analysis aims to quantitatively review the literature that assessed the oxidative stress marker total oxidative stress (TOS) and total antioxidant capacity (TAC) in various biological fluids of patients with periodontitis. . Electronic databases were searched for studies that assessed TOS and TAC levels in various biological samples of patients with periodontitis.
RESULTS
From the 1,812 articles identified, 1,754 were excluded based on title and abstract screening due to irrelevance to the topic of interest. A full-text assessment of the remaining 58 articles led to the selection of 42 articles that satisfied the inclusion criteria. Of these, only 24 studies had consistent data for quantitative analysis. The periodontitis group displayed significantly elevated TOS levels ( < 0.05) in serum, gingival crevicular fluid (GCF), and saliva samples in the studies evaluated. In contrast, the periodontitis group exhibited significantly attenuated TAC levels ( < 0.01) compared to healthy controls in plasma, serum, and GCF samples of the studies evaluated, which was insignificant in salivary samples (=0.433). At the same time, the periodontitis group displayed insignificantly elevated TAC levels after periodontal therapy (=0.130).
CONCLUSIONS
The present meta-analysis showed significantly higher TOS and lower TAC in periodontitis, reflecting the elevated oxidative stress level than the control group. . Scientific rationale for the study: The imbalance between oxidants and antioxidants (oxidative stress (OS)) plays a critical role in the onset and progression of periodontitis; the assessment of the relationship between OS-related biomarkers in regional samples and systemic samples of patients with periodontitis helps us to evaluate the periodontal disease progression. The OS biomarker levels can be used to assess periodontal disease and therapeutic efficacy.
Topics: Humans; Antioxidants; Chronic Periodontitis; Oxidative Stress; Oxidants; Gingival Crevicular Fluid; Biomarkers; Free Radicals
PubMed: 37937148
DOI: 10.1155/2023/9949047 -
Proceedings of the National Academy of... Dec 2023It has previously been reported that antioxidant vitamins can help reduce the risk of vision loss associated with progression to advanced age-related macular...
It has previously been reported that antioxidant vitamins can help reduce the risk of vision loss associated with progression to advanced age-related macular degeneration (AMD), a leading cause of visual impairment among the elderly. Nonetheless, how oxidative stress contributes to the development of choroidal neovascularization (CNV) in some AMD patients and geographic atrophy (GA) in others is poorly understood. Here, we provide evidence demonstrating that oxidative stress cooperates with hypoxia to synergistically stimulate the accumulation of hypoxia-inducible factor (HIF)-1α in the retinal pigment epithelium (RPE), resulting in increased expression of the HIF-1-dependent angiogenic mediators that promote CNV. HIF-1 inhibition blocked the expression of these angiogenic mediators and prevented CNV development in an animal model of ocular oxidative stress, demonstrating the pathological role of HIF-1 in response to oxidative stress stimulation in neovascular AMD. While human-induced pluripotent stem cell (hiPSC)-derived RPE monolayers exposed to chemical oxidants resulted in disorganization and disruption of their normal architecture, RPE cells proved remarkably resistant to oxidative stress. Conversely, equivalent doses of chemical oxidants resulted in apoptosis of hiPSC-derived retinal photoreceptors. Pharmacologic inhibition of HIF-1 in the mouse retina enhanced-while HIF-1 augmentation reduced-photoreceptor apoptosis in two mouse models for oxidative stress, consistent with a protective role for HIF-1 in photoreceptors in patients with advanced dry AMD. Collectively, these results suggest that in patients with AMD, increased expression of HIF-1α in RPE exposed to oxidative stress promotes the development of CNV, but inadequate HIF-1α expression in photoreceptors contributes to the development of GA.
Topics: Mice; Animals; Humans; Aged; Retinal Pigment Epithelium; Geographic Atrophy; Hypoxia-Inducible Factor 1; Angiogenesis Inhibitors; Wet Macular Degeneration; Vascular Endothelial Growth Factor A; Visual Acuity; Choroidal Neovascularization; Oxidants; Hypoxia
PubMed: 38055741
DOI: 10.1073/pnas.2302845120