RESUMO
In this work, a protonated graphitic carbon nitride (P-g-C3N4)-coated graphene oxide (GO) composite (GO/P-g-C3N4) was prepared via wet-chemistry exfoliation, followed by a freeze-drying process. The GO/P-g-C3N4 composite was found to have an outstanding photodegradation performance effect on the reactive red 195 (RR195) dye and very strong antibacterial properties. Both the GO structure and the dispersed state of P-g-C3N4 were found to play a significant role in enhancing the photocatalytic activity of GO/P-g-C3N4. The GO/P-g-C3N4 obtained via freeze-drying retained a large number of oxygen-containing groups and showed higher catalytic activity and reusability than the reduced GO (rGO)/g-C3N4 obtained via thermal reduction. Characterization of the samples indicates that GO/P-g-C3N4 has a higher specific surface area and photocurrent density than rGO/g-C3N4; it is likely that these properties lead to the superior photocatalytic activity observed in GO/P-g-C3N4. Adsorption energy calculations indicate that O2 can be readily adsorbed onto the GO surface, which results in stronger oxidizing superoxide anion radicals (â¢O2-) and holes (h+); these active radicals can rapidly degrade RR195 dyes. Moreover, broad-spectrum antibacterial activity (demonstrated against Staphylococcus aureus and Escherichia coli) was observed in the case of the GO/P-g-C3N4 composite irradiated with visible light. This work offers new insights into the design of cost-effective g-C3N4-based photocatalysts for environmental remediation.
Assuntos
Antibacterianos , Antibacterianos/farmacologia , Antibacterianos/química , Catálise , Escherichia coli , Fotólise , Oxidantes FotoquímicosRESUMO
The short-term association between ambient air pollution and hospital admissions for ischemic stroke is not fully understood. We examined the association between four regularly measured major ambient air pollutants, i.e., sulfur dioxide (SO2), nitrogen dioxide (NO2), photochemical oxidants (Ox), and particulate matter with aerodynamic diameters ≤ 2.5 µm (PM2.5), and hospital admissions for ischemic stroke by analyzing 3 years of nationwide claims data from 97 cities in Japan. We first estimated city-specific results by using generalized additive models with a quasi-Poisson regression, and we obtained the national average by combining city-specific results with the use of random-effect models. We identified a total of 335,248 hospital admissions for ischemic stroke during the 3-year period. Our analysis results demonstrated that interquartile range increases in the following four ambient air pollutants were significantly associated with hospital admissions for ischemic stroke on the same day: SO2 (1.05 ppb), 1.05% (95% CI: 0.59-1.50%); NO2 (6.40 ppb), 1.10% (95% CI: 0.61-1.59%); Ox (18.32 ppb), 1.43% (95% CI: 0.81-2.06%); and PM2.5 (7.86 µg/m3), 0.90% (95% CI: 0.35-1.45%). When the data were stratified by the hospital admittees' medication use, we observed stronger associations with SO2, NO2, and PM2.5 among the patients who were taking antihypertensive drugs and weaker associations with SO2, NO2, and Ox among those taking antiplatelet drugs. Short-term exposure to ambient air pollution was associated with increased hospital admissions for ischemic stroke, and medication use and season may modify the association.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , AVC Isquêmico , Oxidantes Fotoquímicos , Humanos , Dióxido de Nitrogênio/análise , Cidades , Japão/epidemiologia , Dióxido de Enxofre/análise , Oxidantes Fotoquímicos/análise , Anti-Hipertensivos/análise , Inibidores da Agregação Plaquetária/análise , Poluição do Ar/análise , Material Particulado/análise , Poluentes Atmosféricos/análise , Hospitais , China , Exposição Ambiental/análiseRESUMO
While photochemical oxidants (Ox = O3+ NO2) are known to increase asthma flare-ups, there is a paucity of studies of the Japanese population, especially for Tokyo residents. We used data on asthma cases (n = 7,455) from ambulance dispatches in Tokyo, 2015-2016. Variables included date and time of incidence, age, sex, occurrence location at the ward (ku) level, and the symptom/cause of dispatch as recorded by paramedics. Ox data were obtained from the nearest air quality monitoring station to the occurrence location, then linked them with the outcomes based on occurrence date. We directly incorporated a distributed lag model into a bi-directional case-crossover study design controlling for ambient temperature and day of week. A 10-ppb increase in Ox for lag days 0-3 was associated with a 5.51% (95% CI: 0.13 to 11.18) increase in ambulance dispatches related to asthma. The association was strongest on lag day 1 (4.67%, 95% CI: 0.51 to 9.00). Exposure to high levels of Ox was associated with increased ambulance dispatches related to asthma exacerbations in Tokyo, Japan.
Assuntos
Poluentes Atmosféricos , Poluição do Ar , Asma , Oxidantes Fotoquímicos , Ozônio , Poluentes Atmosféricos/análise , Ambulâncias , Asma/induzido quimicamente , Asma/epidemiologia , Estudos Cross-Over , Humanos , Tóquio/epidemiologiaRESUMO
This study aimed to investigate the effect of ozone ultrafine bubble water (OUFBW) on the formation and growth of Candida albicans (C. albicans) biofilms and surface properties of denture base resins. OUFBWs were prepared under concentrations of 6 (OUFBW6), 9 (OUFBW9), and 11 ppm (OUFBW11). Phosphate buffered saline and ozone-free electrolyte aqueous solutions (OFEAS) were used as controls. Acrylic resin discs were made according to manufacturer instructions, and C. albicans was initially cultured on the discs for 1.5 h. A colony forming unit (CFU) assay was performed by soaking the discs in OUFBW for 5 min after forming a 24-h C. albicans biofilm. The discs after initial attachment for 1.5 h were immersed in OUFBW and then cultured for 0, 3, and 5 h. CFUs were subsequently evaluated at each time point. Moreover, a viability assay, scanning electron microscopy (SEM), Alamar Blue assay, and quantitative real-time polymerase chain reaction (qRT-PCR) test were performed. To investigate the long-term effects of OUFBW on acrylic resin surface properties, Vickers hardness (VH) and surface roughness (Ra) were measured. We found that OUFBW9 and OUFBW11 significantly degraded the formed 24-h biofilm. The time point CFU assay showed that C. albicans biofilm formation was significantly inhibited due to OUFBW11 exposure. Interestingly, fluorescence microscopy revealed that almost living cells were observed in all groups. In SEM images, the OUFBW group had lesser number of fungi and the amount of non-three-dimensional biofilm than the control group. In the Alamar Blue assay, OUFBW11 was found to suppress Candida metabolic function. The qRT-PCR test showed that OUFBW down-regulated ALS1 and ALS3 expression regarding cell-cell, cell-material adhesion, and biofilm formation. Additionally, VH and Ra were not significantly different between the two groups. Overall, our data suggest that OUFBW suppressed C. albicans growth and biofilm formation on polymethyl methacrylate without impairing surface properties.
Assuntos
Biofilmes/crescimento & desenvolvimento , Candida albicans/crescimento & desenvolvimento , Candidíase/tratamento farmacológico , Ozônio/administração & dosagem , Água/química , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candidíase/microbiologia , Humanos , Oxidantes Fotoquímicos/administração & dosagem , Polimetil Metacrilato/química , Propriedades de SuperfícieRESUMO
Low-ozone doses cause alterations in the oxidation-reduction mechanisms due to the increase in reactive oxygen species, alter cell signaling, and produce deleterious metabolic responses for cells. Adenosine 5'triphosphate (ATP) can act as a mediator in intercellular communication between neurons and glial cells. When there is an increase in extracellular ATP, a modification is promoted in the regulation of inflammation, energy metabolism, by affecting the intracellular signaling pathways that participate in these processes. The objective of this work was to study changes in the P2X7 receptor, and their relationship with the inflammatory response and energy metabolism, in a model of progressive neurodegeneration in the hippocampus of rats chronically exposed to low-ozone doses. Therefore, 72 male rats were exposed to low-ozone doses for different periods of time. After exposure to ozone was finished, rats were processed for immunohistochemical techniques, western blot, quantitative polymerase chain reaction (qPCR), and histological techniques for periodic acid-Schiff staining. The results showed immunoreactivity changes in the amount of the P2X7 protein. There was an increase in phosphorylation for glycogen synthase kinase 3-ß (GSK3-ß) as treatment continued. There were also increases in 27 interleukin 1 beta (IL-1 ß) and interleukin 17 (IL-17) and a decrease in interleukin 10 (IL-10). Furthermore, neuronal glycogen was found at 30 and 60 days, and an increase in caspase 3. An increase in mRNA was also shown for the P2X7 gene at 60 days, and GSK3-ß at 90 days of exposure. In conclusion, these results suggest that repeated exposure to low-ozone doses, such as those that can occur during highly polluted days, causes a state of oxidative stress, leading to alterations in the P2X7 receptors, which promote changes in the activation of signaling pathways for inflammatory processes and cell death, converging at a progressive neurodegeneration process, as may be happening in Alzheimer's disease.
Assuntos
Hipocampo/patologia , Doenças Neurodegenerativas/patologia , Doenças Neuroinflamatórias/patologia , Neurônios/patologia , Ozônio/toxicidade , Receptores Purinérgicos P2X7/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Interleucina-1beta/metabolismo , Masculino , Doenças Neurodegenerativas/induzido quimicamente , Doenças Neurodegenerativas/metabolismo , Doenças Neuroinflamatórias/induzido quimicamente , Doenças Neuroinflamatórias/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Oxidantes Fotoquímicos/toxicidade , Estresse Oxidativo , Ratos , Ratos Wistar , Receptores Purinérgicos P2X7/genéticaRESUMO
Photochemical pollutants pose a substantial threat to human health in both outdoor and indoor environments. Herein, we prepare a class of gold nanoparticle-based colorimetric sensor arrays on optimized hydrophobic substrates using a simple pin-printing method for accurate identification and quantification of various gas-phase oxidants, as these microdetectors are low cost, sensitive, and easy to fabricate. For an array of AuNP sensors modified with various thiol-terminated ligands, a unique and distinguishable change in color (i.e., red, green, and blue response patterns) was obtained for each specific pollutant for molecular fingerprinting. Remarkable discrimination among 15 gases at a fairly low vapor concentration (i.e., 500 ppb) was illustrated using standard chemometric methods. Using digital imaging, the AuNP colorimetric sensor array offers ultrasensitive dosimetric identification of gas-phase oxidants relevant to outdoor and indoor air pollution, with limits of detection generally at sub-ppb levels for 2 h measurement. As a practical application, the sensor array is able to predict the overall air quality in indoor office environments over 24 h. Such sensor array based on chemically induced sintering of nanoparticles has significant implications for the development of nanosensors used in continuous monitoring of potential airborne pollutants at low concentrations from a large number of locations in a cost-effective manner.
Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Nanopartículas Metálicas , Oxidantes Fotoquímicos , Poluentes Atmosféricos/análise , Poluição do Ar em Ambientes Fechados/análise , Colorimetria , Ouro , HumanosRESUMO
Oxygen-ozone (O2-O3) therapy is increasingly applied as a complementary/adjuvant treatment for several diseases; however, the biological mechanisms accounting for the efficacy of low O3 concentrations need further investigations to understand the possibly multiple effects on the different cell types. In this work, we focused our attention on fibroblasts as ubiquitous connective cells playing roles in the body architecture, in the homeostasis of tissue-resident cells, and in many physiological and pathological processes. Using an established human fibroblast cell line as an in vitro model, we adopted a multimodal approach to explore a panel of cell structural and functional features, combining light and electron microscopy, Western blot analysis, real-time quantitative polymerase chain reaction, and multiplex assays for cytokines. The administration of O2-O3 gas mixtures induced multiple effects on fibroblasts, depending on their activation state: in non-activated fibroblasts, O3 stimulated proliferation, formation of cell surface protrusions, antioxidant response, and IL-6 and TGF-ß1 secretion, while in LPS-activated fibroblasts, O3 stimulated only antioxidant response and cytokines secretion. Therefore, the low O3 concentrations used in this study induced activation-like responses in non-activated fibroblasts, whereas in already activated fibroblasts, the cell protective capability was potentiated.
Assuntos
Fibroblastos/efeitos dos fármacos , Oxidantes Fotoquímicos/farmacologia , Ozônio/farmacologia , Linhagem Celular , Proliferação de Células , Fibroblastos/metabolismo , Fibroblastos/fisiologia , Fibroblastos/ultraestrutura , Heme Oxigenase-1/metabolismo , Humanos , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Fator de Crescimento Transformador beta/metabolismoRESUMO
Low-dose ozone acts as a bioregulator in chronic inflammatory diseases, biochemically characterized by high oxidative stress and a blocked regulation. During systemic applications, "Ozone peroxides" are able to replace H2O2 in its specific function of regulation, restore redox signaling, and improve the antioxidant capacity. Two different mechanisms have to be understood. Firstly, there is the direct mechanism, used in topical treatments, mostly via radical reactions. In systemic treatments, the indirect, ionic mechanism is to be discussed: "ozone peroxide" will be directly reduced by the glutathione system, informing the nuclear factors to start the regulation. The GSH/GSSG balance outlines the ozone dose and concentration limiting factor. Antioxidants are regulated, and in the case of inflammatory diseases up-regulated; cytokines are modulated, here downregulated. Rheumatoid arthritis RA as a model for chronic inflammation: RA, in preclinical and clinical trials, reflects the pharmacology of ozone in a typical manner: SOD (superoxide dismutase), CAT (catalase) and finally GSH (reduced glutathione) increase, followed by a significant reduction of oxidative stress. Inflammatory cytokines are downregulated. Accordingly, the clinical status improves. The pharmacological background investigated in a remarkable number of cell experiments, preclinical and clinical trials is well documented and published in internationally peer reviewed journals. This should encourage clinicians to set up clinical trials with chronic inflammatory diseases integrating medical ozone as a complement.
Assuntos
Antioxidantes/administração & dosagem , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Inflamação/tratamento farmacológico , Estresse Oxidativo , Ozônio/administração & dosagem , Animais , Artrite Experimental/etiologia , Artrite Experimental/patologia , Artrite Reumatoide/etiologia , Artrite Reumatoide/patologia , Catalase/metabolismo , Citocinas/metabolismo , Glutationa/metabolismo , Humanos , Inflamação/etiologia , Inflamação/patologia , Oxidantes Fotoquímicos/administração & dosagem , Oxirredução , RatosRESUMO
Some chemicals have been reported to cause metabolite-related phototoxicity, and this study aimed to verify the applicability of photosafety assessment based on photochemical and pharmacokinetic properties to evaluate the metabolite-related phototoxicity risk. The phototoxic risk of imipramine (IMI) and its metabolite, desipramine (DMI), was evaluated by photochemical and pharmacokinetic analyses. IMI and DMI were found to have similar photoreactivities based on the generation of reactive oxygen species. The skin concentrations of IMI and DMI reached maximal levels at approximately 1 and 4 h, respectively, after oral administration of IMI (10 mg/kg), and DMI showed high skin deposition compared with IMI. According to the results, DMI was identified as a contributor to phototoxicity induced by orally-taken IMI. In in vivo phototoxicity testing, ultraviolet A irradiation from 3 to 6 h after oral administration of IMI (100 mg/kg) caused more potent phototoxic reactions compared with that from 0 to 3 h, and DMI yielded by metabolism of IMI would be associated with phototoxic reactions caused by orally-administered IMI. In addition to the data on IMI, a parent chemical, photochemical and pharmacokinetic profiling of its metabolite, DMI, led to reliable phototoxicity prediction of orally-administered IMI. Thus, characterization of the photosafety of metabolites would generate reliable information on the phototoxicity risk of parent chemicals, and the proposed strategy may facilitate comprehensive photosafety assessment of drug candidates in pharmaceutical development.
Assuntos
Dermatite Fotoalérgica/etiologia , Dermatite Fotoalérgica/fisiopatologia , Dermatite Fototóxica/etiologia , Dermatite Fototóxica/metabolismo , Desipramina/efeitos adversos , Imipramina/efeitos adversos , Raios Ultravioleta/efeitos adversos , Administração Oral , Desipramina/metabolismo , Imipramina/metabolismo , Oxidantes Fotoquímicos/metabolismo , Espécies Reativas de Oxigênio/metabolismoRESUMO
Stimuli-responsive recombinant elastin-like polypeptides (ELPs) are artificial protein polymers derived from the hydrophobic domain of tropoelastin that have attracted significant interest for drug delivery and tissue engineering applications. In the present study, we have conjugated a photosensitizer (PS) to a hydrophobic methionine-containing ELP scaffold, which upon reaction with singlet oxygen (1O2) is transformed into a hydrophilic sulfoxide derivative facilitating the disassembly of photosensitizer-delivery particles during the photodynamic therapy (PDT) process. A peripherally substituted carboxy-Zn(II)-phthalocyanine derivative (TT1) bearing a carboxyl group directly linked to the Pc-ring, and presenting an absorption maximum around 680 nm, was selected as PS which simultaneously acted as a photooxidation catalyst. A TT1-ELP[M1V3-40] conjugate was prepared from ELP[M1V3-40] modified with an alkyne group at the N-terminal chain end, and from TT1-amide-C3-azide by copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. This innovative model photooxidation sensitive PS delivery technology offers promising attributes in terms of temperature-controlled particle formation and oxidation-triggered release, narrow molar mass distribution, reproducibility, scalability, non-immunogenicity, biocompatibility, and biodegradability for pharmaceutical applications in an effort to improve the clinical effectiveness of PDT treatments.
Assuntos
Elastina/química , Oxidantes Fotoquímicos/farmacologia , Peptídeos/farmacologia , Humanos , Micelas , Estrutura Molecular , Oxidantes Fotoquímicos/química , Oxirredução , Peptídeos/química , FotoquimioterapiaRESUMO
Considerable attention has been drawn to predict a photosafety hazard on new chemicals. A number of phototoxins tend to generate reactive oxygen species (ROS) via energy transfer mechanisms following UV/VIS excitation, including superoxide and singlet oxygen. Then, ROS assay has been designed to assess photoreactivity of pharmaceuticals, of which the principle is to monitor types I and II photochemical reactions of the test chemicals when exposed to simulated sunlight. This simple analytical test could be used to screen potential chemical scaffolds, leads, and candidate drugs to identify and/or select away from those having phototoxic potential. The validation study for the ROS assay has been being carried out by the Japan Pharmaceutical Manufacturers Association (JPMA), supervised by the Japanese Center for the Validation of Alternative Methods (JaCVAM). Although several false positives appeared, the ROS assay on 42 coded chemicals has provided no false negative predictions. The validation study tentatively indicates satisfactory outcomes in terms of transferability, intra- and inter-laboratory variability, and predictive capacity. Thus, a negative result in this ROS assay would indicate a very low probability of phototoxicity, whereas a positive result would be a flag for follow-up assessment. Upon international harmonization activities supported by several agencies and industrial groups, ROS assay was successfully adopted as International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) S10 guideline (2014) and Organisation for Economic Co-operation and Development (OECD) test guideline 495 (2019).
Assuntos
Dermatite Fototóxica/diagnóstico , Cooperação Internacional , Oxidantes Fotoquímicos/análise , Preparações Farmacêuticas/química , Espécies Reativas de Oxigênio/análise , Testes de Toxicidade/métodos , Testes de Toxicidade/normas , Dermatite Fototóxica/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Guias como Assunto , Humanos , SegurançaRESUMO
Fast photochemical oxidation of proteins (FPOP) has demonstrated the ability to inform on the higher order structure of proteins. Recent technological advances have extended FPOP to live cells (IC-FPOP) using multiple cell lines and in vivo (IV-FPOP) using C. elegans. These innovations allow proteins to be studied in their native cellular environment. Hydroxyl radicals are generated via the photoloysis of hydrogen peroxide. Hydrogen peroxide is a signaling molecule that can induce changes to some proteins in the cell limiting the proteins that can be studied by IC-FPOP. Here, we evaluate the sulfate radical anion as a footprinting label in IC-FPOP with sodium persulfate as the precursor. Our findings show a 1.5-fold increase in the number of modified proteins compared to IC-FPOP using hydroxyl radicals at the same precursor concentration demonstrating the amenability of this radical with IC-FPOP.
Assuntos
Indicadores e Reagentes/química , Proteínas , Sulfatos/química , Células HEK293 , Humanos , Oxidantes Fotoquímicos , Oxirredução , Pegadas de Proteínas/métodos , Proteínas/análise , Proteínas/química , Compostos de Sódio/químicaRESUMO
An increasing amount of reports in the literature is showing that medical ozone (O3) is used, with encouraging results, in treating COVID-19 patients, optimizing pain and symptoms relief, respiratory parameters, inflammatory and coagulation markers and the overall health status, so reducing significantly how much time patients underwent hospitalization and intensive care. To date, aside from mechanisms taking into account the ability of O3 to activate a rapid oxidative stress response, by up-regulating antioxidant and scavenging enzymes, no sound hypothesis was addressed to attempt a synopsis of how O3 should act on COVID-19. The knowledge on how O3 works on inflammation and thrombosis mechanisms is of the utmost importance to make physicians endowed with new guns against SARS-CoV2 pandemic. This review tries to address this issue, so to expand the debate in the scientific community.
Assuntos
Tratamento Farmacológico da COVID-19 , Oxidantes Fotoquímicos/farmacologia , Ozônio/farmacologia , SARS-CoV-2/efeitos dos fármacos , Humanos , Estresse Oxidativo/efeitos dos fármacosRESUMO
Functional nanocomposites with biopolymers and zinc oxide (ZnO) nanoparticles is an emerging application of photocatalysis in antifouling coatings. The reduced chemical stability of ZnO in the acidic media in which chitosan is soluble affects the performance of chitosan nanocomposites in antifouling applications. In this study, a thin shell of amorphous tin dioxide (SnOx) was grown on the surface of ZnO to form ZnO-SnOx core-shell nanoparticles that improved the chemical stability of the photocatalyst nanoparticles, as examined at pH 3 and 6. The photocatalytic activity of ZnO-SnOx in the degradation of methylene blue (MB) dye under visible light showed a higher efficiency than that of ZnO nanoparticles due to the passivation of electronic defects. Chitosan-based antifouling coatings with varying percentages of ZnO or ZnO-SnOx nanoparticles, with or without the glutaraldehyde (GA) crosslinking of chitosan, were developed and studied. The incorporation of photocatalysts into the chitosan matrix enhanced the thermal stability of the coatings. Through a mesocosm study using running natural seawater, it was found that chitosan/ZnO-SnOx/GA coatings enabled better inhibition of bacterial growth compared to chitosan coatings alone. This study demonstrates the antifouling potential of chitosan nanocomposite coatings containing core-shell nanoparticles as an effective solution for the prevention of biofouling.
Assuntos
Quitosana/química , Nanocompostos/química , Óxido de Zinco/química , Antibacterianos/farmacologia , Incrustação Biológica/prevenção & controle , Biopolímeros , Microscopia Eletrônica de Varredura/métodos , Nanopartículas/química , Oxidantes Fotoquímicos/química , Compostos de Estanho/químicaRESUMO
A metal-free regioselective C(sp3)-H amination of amides using N-haloimides in the presence of lithium tert-butoxide and visible light is presented herein. This photoexcited approach is straightforward, and it aminates a wide variety of amides under mild conditions without the use of photocatalysts, external radical initiators, or oxidants. A halogen-bonded intermediate between the tert-butoxide base and the N-haloimide is proposed to be responsible for the increased photoreactivity. Calculations show that the formation of this electron donor-acceptor complex presents an exergonic energy profile.
Assuntos
Amidas/química , Oxidantes Fotoquímicos/química , Oxidantes/química , Aminação , Estrutura MolecularRESUMO
PURPOSE: Histidine (His) undergoes light-induced reactions such as oxidation, crosslinking and addition. These reactions are initiated by singlet oxygen (1O2) to generate His photo-oxidation products, which are subject to nucleophilic attack by a non-oxidized His residue from another protein or by nucleophilic buffer components such as Tris and His. This report aims to identify light-induced His-adducts to a monoclonal antibody (mAb-1) due to the reaction of His molecules in the buffer with the photooxidized His residues under ICH light conditions. Since polysorbate-20 (PS-20) is a commonly used excipient in biotherapeutics formulation, it is also important to study the impact of PS-20 concentration on protein photostability. RESULTS: We identified and characterized light-induced His-adducts of mAb-1 by LC-MS/MS. We showed that the levels of light-induced His-adducts generally correlate with the solvent accessibility of His residues in the protein. In addition, the presence of PS-20 at concentrations commonly used in protein drug formulations can significantly increase the levels of light-induced His-adducts. CONCLUSIONS: Since His residues are present in a conserved region in the Fc domain, and may be present in the complementarity-determining region (CDR), the impact on the biological functions of the His-adducts observed here should be further studied to evaluate the risk of their presence.
Assuntos
Histidina/química , Imunoglobulina G/química , Oxidantes Fotoquímicos/química , Polissorbatos/química , Sequência de Aminoácidos , Cromatografia Líquida de Alta Pressão , Composição de Medicamentos , Excipientes/química , Oxirredução , Agregados Proteicos , Conformação Proteica , Desnaturação Proteica , Espectrometria de Massas em TandemRESUMO
9H-Xanthenes, 9H-thioxanthenes and 9,10-dihydroacridines can be easily oxidized to the corresponding xanthones, thioxanthones and acridones, respectively, by a simple photo-oxidation procedure carried out using molecular oxygen as oxidant under the irradiation of visible blue light and in the presence of riboflavin tetraacetate as a metal-free photocatalyst. The obtained yields are high or quantitative.
Assuntos
Acridonas/síntese química , Oxigênio/química , Tioxantenos/síntese química , Xantonas/síntese química , Acridonas/química , Acridonas/efeitos da radiação , Luz , Metais/química , Oxidantes Fotoquímicos/química , Oxidantes Fotoquímicos/farmacologia , Oxirredução/efeitos da radiação , Tioxantenos/química , Tioxantenos/efeitos da radiação , Xantonas/química , Xantonas/efeitos da radiaçãoRESUMO
Ultraviolet B (UVB) light corresponds to 5% of ultraviolet radiation. It is more genotoxic and mutagenic than UVA and causes direct and indirect cellular damage through the generation of reactive oxygen species (ROS). Even after radiation, ROS generation may continue through activation of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) enzyme. Long-term exposure can progress to premature skin aging and photocarcinogenesis. To prevent damage that is caused by UVB radiation, several studies have focused on the topical administration of compounds that have antioxidant properties. 2-Acetylphenothiazine (ML171) is a potent and selective inhibitor of NOX1. The present study investigated the antioxidant potential and photoprotective ability of ML171 in UVB-irradiated L929 fibroblasts. ML171 had considerable antioxidant activity in both the DPPH⢠and xanthine/luminol/xanthine oxidase assays. ML171 did not induce cytotoxicity in L929 fibroblasts and increased the viability of UVB-irradiated cells. ML171 also inhibited ROS production, the enzymatic activity of NOX, depolarization of the mitochondrial membrane, and DNA damage. Additionally, ML171 protected cell membrane integrity and induced fibroblast migration. These results suggest that the incorporation of ML171 in topical administration systems may be a promising strategy to mitigate UVB-induced oxidative damage in L929 fibroblasts.
Assuntos
Antioxidantes/química , Fibroblastos/efeitos da radiação , Oxidantes Fotoquímicos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fenotiazinas/química , Antioxidantes/farmacologia , Apoptose/efeitos da radiação , Linhagem Celular , Dano ao DNA/efeitos da radiação , Fibroblastos/citologia , Humanos , Peroxidação de Lipídeos/efeitos da radiação , NADPH Oxidases/metabolismo , Oxirredução , Fenotiazinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Pele , Raios UltravioletaRESUMO
Soybean (Glycine max) production is seriously threatened by ground-level ozone (O3) pollution. The goal of our study is to summarize the impacts of O3 on physiology, growth, yield, and quality of soybean, as well as root parameters. We performed meta-analysis on the collated 48 peer-reviewed papers published between 1980 and 2019 to quantitatively summarize the response of soybean to elevated O3 concentrations ([O3]). Relative to charcoal-filtered air (CF), elevated [O3] significantly accelerated chlorophyll degradation, enhanced foliar injury, and inhibited growth of soybean, evidenced by great reductions in leaf area (-20.8%), biomass of leaves (-13.8%), shoot (-22.8%), and root (-16.9%). Shoot of soybean was more sensitive to O3 than root in case of biomass. Chronic ozone exposure of about 75.5 ppb posed pronounced decrease in seed yield of soybean (-28.3%). In addition, root environment in pot contributes to higher reduction in shoot biomass and yield of soybean. Negative linear relationships were observed between yield loss and intensity of O3 treatment, AOT40. The larger loss in seed yield was significantly associated with higher reduction in shoot biomass and other yield component. This meta-analysis demonstrates the effects of elevated O3 on soybean were pronounced, suggesting that O3 pollution is still a soaring threat to the productivity of soybean in regions with high ozone levels.
Assuntos
Poluentes Atmosféricos/efeitos adversos , Produtos Agrícolas/efeitos dos fármacos , Glycine max/efeitos dos fármacos , Oxidantes Fotoquímicos/efeitos adversos , Ozônio/efeitos adversos , Poluentes Atmosféricos/análise , Biomassa , Produtos Agrícolas/crescimento & desenvolvimento , Produtos Agrícolas/metabolismo , Relação Dose-Resposta a Droga , Oxidantes Fotoquímicos/análise , Ozônio/análise , Estruturas Vegetais/efeitos dos fármacos , Estruturas Vegetais/crescimento & desenvolvimento , Estruturas Vegetais/metabolismo , Sementes/efeitos dos fármacos , Sementes/crescimento & desenvolvimento , Glycine max/crescimento & desenvolvimento , Glycine max/metabolismoRESUMO
Severe forms of COVID-19 can evolve into pneumonia, featured by acute respiratory failure due to acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In viral diseases, the replication of viruses is seemingly stimulated by an imbalance between pro-oxidant and antioxidant activity as well as by the deprivation of antioxidant mechanisms. In COVID-19 pneumonia, oxidative stress also appears to be highly detrimental to lung tissues. Although inhaling ozone (O3) gas has been shown to be toxic to the lungs, recent evidence suggests that its administration via appropriate routes and at small doses can paradoxically induce an adaptive reaction capable of decreasing the endogenous oxidative stress. Ozone therapy is recommended to counter the disruptive effects of severe COVID-19 on lung tissues, especially if administered in early stages of the disease, thereby preventing the progression to ARDS.