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1.
Biochemistry (Mosc) ; 84(11): 1233-1246, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31760914

RESUMO

Cellular redox homeostasis involves a combination of redox processes and corresponding regulatory systems and represents an important factor ensuring cell viability. Redox-dependent regulation of cellular processes is a multi-level system including not only proteins and enzyme complexes, but also non-coding RNAs, among which an important role belongs to microRNAs. The review focuses on the involvement of miRNAs in the redox-dependent regulation of both ROS (reactive oxygen species)-generating enzymes and antioxidant enzymes with special emphasis on the effects of miRNAs on redox-dependent processes in tumor cells. The impact of ROS on the miRNA expression and the role of the ROS/miRNA feedback regulation in the cell redox state are discussed.


Assuntos
MicroRNAs/metabolismo , Animais , Humanos , MicroRNAs/química , Neoplasias/metabolismo , Neoplasias/patologia , Oxirredução , Estresse Oxidativo , Oxirredutases/metabolismo , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/metabolismo
2.
Biochemistry (Mosc) ; 84(11): 1268-1279, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31760917

RESUMO

The review describes the use of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) inhibitors to study the enzyme and to suppress its activity in various cell types. The main problem of selective GAPDH inhibition is a highly conserved nature of the enzyme active site and, especially, Cys150 environment important for the catalytic action of cysteine sulfhydryl group. Numerous attempts to find specific inhibitors of sperm GAPDH and enzymes from Trypanosoma sp. and Mycobacterium tuberculosis that would not inhibit GAPDH of somatic mammalian cells have failed, which has pushed researchers to search for new ways to solve this problem. The sections of the review are devoted to the studies of GAPDH inactivation by reactive oxygen species, glutathione, and glycating agents. The final section discusses possible effects of GAPDH inhibition and inactivation on glycolysis and related metabolic pathways (pentose phosphate pathway, uncoupling of the glycolytic oxidation and phosphorylation, etc.).


Assuntos
Inibidores Enzimáticos/química , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Antioxidantes/química , Antioxidantes/metabolismo , Inibidores Enzimáticos/metabolismo , Glutationa/química , Glutationa/metabolismo , Gliceraldeído-3-Fosfato Desidrogenases/antagonistas & inibidores , Glicosilação , Mycobacterium tuberculosis/enzimologia , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/metabolismo , Trypanosoma/enzimologia
3.
J Photochem Photobiol B ; 201: 111633, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31726378

RESUMO

In the present study, we assessed the oral mucosal irritation potential of antimicrobial chemotherapy involving hydrogen peroxide (H2O2) photolysis with a 405-nm laser device at an output power of ≥100 mW in hamsters. Twenty-four cheek pouches from 12 male Syrian hamsters received 7-min treatment with pure water (PW), 3% H2O2, laser irradiation of PW at 100 mW, laser irradiation of 3% H2O2 at 100 mW, laser irradiation of PW at 200 mW, or laser irradiation of 3% H2O2 at 200 mW (n = 4 each). The diameter of the irradiation area was set at 3 mm; accordingly, the calculated irradiances (optical power densities) of the 100- and 200-mW laser lights were approximately 1400 and 2800 mW/cm2, respectively. In addition, 12 cheek pouches from six animals received laser irradiation of 3% H2O2 at 100 mW for 1, 3, or 5 min (n = 4 each). Each treatment was repeated three times at 1-h intervals. Macroscopic and histological changes were evaluated 24 h after the last treatment. In addition, in vitro bactericidal activity of the treatment against periodontal pathogens was evaluated. We found that 405-nm laser irradiation of 3% H2O2 caused moderate to severe oral mucosal irritation when performed at powers of 100 and 200 mW for ≥3 min, while the same treatment performed at 100 mW for 1 min resulted in mild irritation. Moreover, 1-min H2O2 photolysis at 100 mW caused a >4-log decrease in viable bacterial counts. These findings suggest that 1-min H2O2 photolysis, which can effectively kill periodontal pathogens, may be acceptable when a 405-nm laser device is used at 100 mW. However, use of the laser at a lower power would be preferable for the prevention of unnecessary oral mucosal irritation.


Assuntos
Anti-Infecciosos/farmacologia , Peróxido de Hidrogênio/farmacologia , Lasers , Mucosa Bucal/efeitos dos fármacos , Fotólise/efeitos dos fármacos , Células 3T3-L1 , Animais , Anti-Infecciosos/química , Anti-Infecciosos/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Cricetinae , Espectroscopia de Ressonância de Spin Eletrônica , Masculino , Camundongos , Mucosa Bucal/metabolismo , Mucosa Bucal/efeitos da radiação , Periodontite/tratamento farmacológico , Fotólise/efeitos da radiação , Porphyromonas gingivalis/efeitos dos fármacos , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/metabolismo , Streptococcus mutans/efeitos dos fármacos
4.
Chem Commun (Camb) ; 55(96): 14534-14537, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31740902

RESUMO

Fe-N/C single atom catalysts (SACs) exhibit peroxidase-like, oxidase-like, catalase-like, and glutathione peroxidase-like activity. Fe-N/C SACs are successfully applied to control the intracellular H2O2 level. This study not only explores the types of SACs mimicking enzymes but also provides opportunities for SACs in biomedical and other bioengineering applications.


Assuntos
Materiais Biomiméticos/química , Carbono/química , Ferro/química , Nitrogênio/química , Espécies Reativas de Oxigênio/química , Materiais Biomiméticos/metabolismo , Materiais Biomiméticos/farmacologia , Catalase/química , Catalase/metabolismo , Catálise , Sobrevivência Celular/efeitos dos fármacos , Glutationa Peroxidase/química , Glutationa Peroxidase/metabolismo , Células HeLa , Humanos , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Oxirredução , Porfirinas/química , Espécies Reativas de Oxigênio/metabolismo
5.
Cell Physiol Biochem ; 53(6): 921-932, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31778305

RESUMO

BACKGROUND/AIMS: Lysophosphatidic acid (LPA) is a phospholipid signal molecule that regulates many cellular processes both physiological and pathological. Moreover, its high plasma concentrations are toxic for several cellular types, including erythrocytes (RBC), as it acts as a pro-thrombotic and pro-atherogenic agent. It is therefore essential to explore the potential protective role of nutrition in protecting cells from the possible toxic effects of high plasma concentrations of LPA by testing bioactive nutrients. In particular, our focus was on hydroxytyrosol (HT), a phenolic antioxidant occurring naturally in virgin olive oil, investigating its possible protective effect in preventing LPA-induced programmed cell death (eryptosis) in human RBC. METHODS: Intact RBC were incubated in the presence of 2.5 µM LPA and increasing concentrations of HT. Phosphatidylserine (PS) exposure with cell shrinkage, influx of extracellular calcium (Ca2+), adenosine triphosphate (ATP) and glutathione levels were measured by FACS analysis. In addition, confocal laser scanning microscopy was used to determine RBC morphological alterations, as well as microvesicle formation. RESULTS: Our study confirms that LPA-induced eryptosis is characterized by PS exposure at the cell surface, with cell shrinkage and ATP and glutathione depletion; (Ca2+) influx is also a key event that triggers eryptosis. Here we report for the first time that cell co-incubation with LPA and in quantities as low as 0.1 µM HT causes a significant decrease in PS-exposing RBC, in addition to providing significant protection from the decrease in cell volume. Moreover, treatment of RBC with HT counters the influx of extracellular Ca2+ and completely restores ATP and glutathione content at 1 µM. Finally, under the same experimental conditions, HT exerts a protective effect on RBC morphological changes and microvescicle release, completely restoring the typical biconcave shape at 1 µM. CONCLUSION: Taken together, the findings reported in this paper point to a novel biological effect for HT in preventing programmed suicidal death in anucleated cells and indicate that prevention from LPA toxic effects may represent an additional mechanism responsible for the health-promoting effect of this dietary phenol which has been claimed, particularly related to cardiovascular diseases.


Assuntos
Eriptose/efeitos dos fármacos , Lisofosfolipídeos/toxicidade , Álcool Feniletílico/análogos & derivados , Fosfatidilserinas/farmacologia , Trifosfato de Adenosina/metabolismo , Cálcio/metabolismo , Tamanho Celular/efeitos dos fármacos , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Glutationa/metabolismo , Humanos , Álcool Feniletílico/farmacologia , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/metabolismo
6.
Chem Commun (Camb) ; 55(92): 13820-13823, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31664274

RESUMO

A supramolecular nanocapsule was constructed by the ternary host-guest complexation of azobenzene (Azo) and methylviologen (MV) to cucurbit[8]uril (CB[8]) and the subsequent self-assembly. The supramolecular nanocapsule with both glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities can mimic the intracellular enzymatic reactive oxygen species (ROS) defense system.


Assuntos
Antioxidantes/química , Hidrocarbonetos Aromáticos com Pontes/química , Imidazóis/química , Nanocápsulas/química , Células 3T3 , Animais , Compostos Azo/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Glutationa Peroxidase/química , Glutationa Peroxidase/metabolismo , Camundongos , Microscopia Confocal , Nanocápsulas/toxicidade , Paraquat/química , Espécies Reativas de Oxigênio/química , Superóxido Dismutase/química , Superóxido Dismutase/metabolismo
7.
Molecules ; 24(18)2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31547417

RESUMO

Aiming at the assessment of the pro-health, and especially anti-hypochlorite properties of Moringa oleifera species a representative, commercially available Moringa oleifera dietary supplement was used as a substrate for the preparation of aqueous Moringa extract. The anti-hypochlorite activity of the extract was assessed using the hypochlorite-specific coumarin-based fluorescence turn-off sensor, namely 7-diethylamino-coumarin-3-carboxylic acid (7-DCCA). This compound was synthesized via the Knoevenagel condensation of 4-diethylamino-2-hydroxybenzaldehyde with Meldrum's acid and the Moringa extract was employed as a medium and catalyst. Moreover, the total phenolic content (TPC) as well as the reactive oxygen species (ROS)-scavenging ability of the aqueous Moringa extract were determined. The results obtained demonstrated the applicability of Moringa extract as an anti-hypochlorite agent. Additionally, the satisfactory yield of the 7-DCCA obtained suggests the usefulness of the extract as a catalyst and the reaction medium. The antioxidative potential of the extract was notably lower than that of the standard (TROLOX). Determination of TPC in 100 g of the dry weight (DW) of studied material revealed a high number of polyphones present.


Assuntos
Antioxidantes/química , Suplementos Nutricionais , Ácido Hipocloroso/química , Moringa oleifera/química , Extratos Vegetais/química , Catálise , Cumarínicos/síntese química , Cumarínicos/química , Concentração de Íons de Hidrogênio , Fenóis/análise , Extratos Vegetais/análise , Folhas de Planta/química , Espécies Reativas de Oxigênio/química
8.
J Photochem Photobiol B ; 199: 111600, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31473429

RESUMO

Full-aromatic and partially hydrogenated ß-carboline (ßC) derivatives constitute a group of alkaloids widely distributed in a great variety of living systems. In plants and bacteria, tetrahydro-ßCs are the primary product of the Pictet-Spengler enzymatically catalyzed condensation. Tetrahydro-ßC skeleton is further modified giving rise to the formation of a vast set of derivatives including dihydro- and full-aromatic ßCs. However, in most of the cases, the later processes still remain unclear and other sources, such as photo-triggered reactions, deserve to be explored. In this context, the photophysic and photochemistry of 7-methoxy-1-methyl-3,4-dihydro-2H-pyrido[3,4-b]indole or harmaline (Hlina) in aqueous solution is reported herein. UV-visible absorption and fluorescence emission spectroscopy coupled with multivariate data analysis (PARAFAC), HPLC and HRESI-MS techniques were used for both quantitative and qualitative analysis. The formation singlet oxygen and hydrogen peroxide reactive oxygen species (ROS) was quantified and their role together with the influence of pH and oxygen partial pressure on the photochemical degradation of HlinaH+ was assessed. We report herein the first study on photochemical full-aromatization of a dihydro-ßC derivative. These results can shed some light on the ßCs biosynthesis and role in living systems.


Assuntos
Alcaloides/química , Carbolinas/química , Indóis/química , Oxigênio/química , Processos Fotoquímicos , Harmalina/química , Harmina/química , Peróxido de Hidrogênio/química , Concentração de Íons de Hidrogênio , Hidroxilação , Luz , Análise Multivariada , Pressão Parcial , Espécies Reativas de Oxigênio/química , Oxigênio Singlete/química , Relação Estrutura-Atividade
9.
Nucleic Acids Res ; 47(17): 9410-9422, 2019 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-31435651

RESUMO

DNA double-strand breaks (DSBs) resulting from reactive oxygen species generated by exposure to UV and ionizing radiation are characterized by clusters of lesions near break sites. Such complex DSBs are repaired slowly, and their persistence can have severe consequences for human health. We have therefore probed DNA break repair containing a template 8-oxo-7,8-dihydro-2'-guanosine (8OG) by Family X Polymerase µ (Pol µ) in steady-state kinetics and cell-based assays. Pol µ tolerates 8OG-containing template DNA substrates, and the filled products can be subsequently ligated by DNA Ligase IV during Nonhomologous end-joining. Furthermore, Pol µ exhibits a strong preference for mutagenic bypass of 8OG by insertion of adenine. Crystal structures reveal that the template 8OG is accommodated in the Pol µ active site with none of the DNA substrate distortions observed for Family X siblings Pols ß or λ. Kinetic characterization of template 8OG bypass indicates that Pol µ inserts adenosine nucleotides with weak sugar selectivity and, given the high cellular concentration of ATP, likely performs its role in repair of complex 8OG-containing DSBs using ribonucleotides.


Assuntos
Quebras de DNA de Cadeia Dupla/efeitos da radiação , Reparo do DNA por Junção de Extremidades/genética , DNA Polimerase Dirigida por DNA/genética , Guanosina/análogos & derivados , Trifosfato de Adenosina/genética , Dano ao DNA/genética , Dano ao DNA/efeitos da radiação , Reparo do DNA por Junção de Extremidades/efeitos da radiação , DNA Ligase Dependente de ATP/genética , Replicação do DNA/genética , DNA Polimerase Dirigida por DNA/química , Guanosina/genética , Humanos , Mutagênese/efeitos da radiação , Radiação Ionizante , Espécies Reativas de Oxigênio/química , Raios Ultravioleta
10.
Chemistry ; 25(59): 13472-13478, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31393035

RESUMO

A series of water-soluble cationic chalcogenoviologen-based photosensitizers for photodynamic antimicrobial therapy (PDAT) is reported. The Se-containing derivatives (SeMV2+ ) 5 b and 6 b showed good antimicrobial activities due to the presence of chalcogen atoms and a cationic scaffold. The former efficiently enhanced the generation of reactive oxygen species (ROS), and the latter facilitated the ROS delivery to bacteria, resulting in their death. Interestingly, alkyl-modified photosensitizers showed higher antimicrobial activities than commonly reported photosensitizers with quaternary ammonium (QA) groups. In particular, the SeMV2+ (6 b) with excellent antibacterial activities efficiently promoted the healing of infected wounds in mice. Simple yet novel, nontoxic and biocompatible chalcogenoviologens provided a promising strategy to develop new efficient photosensitizers for photodynamic antimicrobial therapy and skin regeneration.


Assuntos
Anti-Infecciosos/química , Cátions/química , Fármacos Fotossensibilizantes/uso terapêutico , Espécies Reativas de Oxigênio/química , Pele/fisiopatologia , Animais , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Camundongos , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Regeneração
11.
J Biomed Nanotechnol ; 15(10): 2045-2058, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31462370

RESUMO

Combining photodynamic therapy (PDT) and chemotherapy can improve anti-cancer efficacy. In this study, a novel copolymer PTPP combining thioketal and protoporphyrin was synthesized and tested for antitumor activity. Self-assembled PTPP micelles loaded with doxorubicin (DOX) showed uniform size, narrow particle size distribution and greater antitumor activity in vivo and in vivo than DOX-loaded micelles made from the commonly used material mPEG-PCL. Under laser irradiation, the photosensitizing protoporphyrin of DOX/PTPP produces abundant reactive oxygen species (ROS) that directly kill tumor cells as well as destroy the micelles themselves, leading to drug release. The ROS and DOX then act synergistically against the tumors. These ROS-responsive, laser-sensitive polymeric micelles may be useful for combining PDT and chemotherapy.


Assuntos
Espécies Reativas de Oxigênio/química , Doxorrubicina , Liberação Controlada de Fármacos , Micelas , Fotoquimioterapia , Polímeros
12.
Chem Commun (Camb) ; 55(67): 9971-9974, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31367709

RESUMO

Photodynamic therapy (PDT) is a clinically approved cancer treatment that uses light, oxygen and a photosensitizer to produce localized reactive oxygen species (ROS). Due to the short lifetime of ROS, the location of the photosensitizer in the cell is believed to be the key determinant governing the outcome of PDT. To explore the effect of direct association between a photosensitizer and DNA a well know DNA-binding dye, DAPI, was converted into a photosensitizer. Br-DAPI - unlike native DAPI - upon irradiation produces ROS. We demonstrate that the ROS are only effective in inducing dsDNA breaks when Br-DAPI is bound to DNA. In cancer cells (A549) Br-DAPI causes rapid light dependent cell death. This work supports the design of photosensitizers which bind with high affinity to the DNA of target cells for potentially more effective PDT.


Assuntos
Bromo/química , DNA/química , Indóis/química , Fármacos Fotossensibilizantes/química , Células A549 , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Dano ao DNA , Corantes Fluorescentes/química , Humanos , Luz , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Estudo de Prova de Conceito , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/metabolismo
13.
Int J Mol Sci ; 20(15)2019 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-31382586

RESUMO

Peroxisomes are ubiquitous organelles with well-defined functions in lipid and reactive oxygen species metabolism, having a significant impact on a large number of important diseases. Growing evidence points to them, in concert with mitochondria, as important players within the antiviral response. In this review we summarize and discuss the recent findings concerning the relevance of peroxisomes within innate immunity. We not only emphasize their importance as platforms for cellular antiviral signaling but also review the current information concerning their role in the control of bacterial infections. We furthermore review the recent data that pinpoints peroxisomes as regulators of inflammatory processes.


Assuntos
Infecções Bacterianas/imunologia , Imunidade Inata , Peroxissomos/imunologia , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Antivirais/uso terapêutico , Infecções Bacterianas/microbiologia , Infecções Bacterianas/virologia , Humanos , Peroxissomos/microbiologia , Peroxissomos/virologia , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/imunologia
14.
Chemistry ; 25(55): 12810-12819, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31298434

RESUMO

The Hg-C bond of MeHgCl, a ubiquitous environmental toxicant, is notoriously inert and exceedingly difficult to cleave. The cleavage of the Hg-C bond of MeHgCl at low temperature, therefore, is of significant importance for human health. Among various bis(imidazole)-2-selones Ln Se (n=1-4, or 6), the three-spacer L3 Se shows extraordinarily high reactivity in the degradation of various mercury alkyls including MeHgCl because of its unique ability to coordinate through κ2 -fashion, in which both the Se atoms simultaneously attack the Hg center of mercury alkyls for facile Hg-C bond cleavage. It has the highest softness (σ) parameter and the lowest HOMO(Ln Se)-LUMO(MeHgX) energy gap and, thus, L3 Se is the most reactive among Ln Se towards MeHgX (X=Cl or I). L3 Se is highly efficient, more than L1 Se, in restoring the activity of antioxidant enzyme glutathione reductase (GR) that is completely inhibited by MeHgCl; 80 % GR activity is recovered by L3 Se relative to 50 % by L1 Se. It shows an excellent cytoprotective effect in liver cells against MeHgCl-induced oxidative stress by protecting vital antioxidant enzymes from inhibition caused by MeHgCl and, thus, does not allow to increase the intracellular reactive oxygen species (ROS) levels. Furthermore, it protects the mitochondrial membrane potential (ΔΨm ) from perturbation by MeHgCl. Major Hg-responsive genes analyses demonstrate that L3 Se plays a significant role in MeHg+ detoxification in liver cells.


Assuntos
Antioxidantes/farmacologia , Glutationa Redutase/metabolismo , Substâncias Perigosas/análise , Mercúrio/análise , Mercúrio/toxicidade , Compostos Organometálicos/química , Espécies Reativas de Oxigênio/metabolismo , Selênio/química , Antioxidantes/química , Citoproteção , Glutationa Redutase/química , Substâncias Perigosas/química , Humanos , Mercúrio/química , Espécies Reativas de Oxigênio/química , Selênio/análise
15.
Mater Sci Eng C Mater Biol Appl ; 103: 109735, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31349428

RESUMO

The enzyme glucose oxidase mediates the oxidation of glucose to produce reactive oxygen species (ROS), such as hydrogen peroxide. This reaction and its products are key to providing honey with its antimicrobial properties. Currently, honey is an adherent, highly viscous product that produces ROS by means of a water-initiated reaction. These properties reduce clinical usability and present a formulation problem for long term stability. This study aims to engineer a water-in-oil emulsion containing an engineered honey (SurgihoneyRO™) that is easy to administer topically and is controllably activated in-situ. Paraffin oil continuous emulsions formulated using the emulsifier polyglycerol polyricinoleate displayed shear-thinning characteristics. Viscosities between 1.4 and 19.3 Pa·s were achieved at a shear rate representative of post-mixing conditions (4.1 s-1) by changing the volume of the dispersed phase (30-60%). Notably, this wide viscosity range will be useful in tailoring future formulations for specific application mechanisms. When exposed to water and shear, these emulsion systems were found to undergo catastrophic phase inversion, evidenced by a change in conductivity from 0 µS in the non-aqueous state, to >180 µS in the sheared, inverted state. Encouragingly, sheared formulations containing ≥50% SurgihoneyRO™ generated sufficient levels of ROS to inhibit growth of clinically relevant Gram-positive and Gram-negative bacteria. This study demonstrates an ability to formulate ROS producing emulsions for use as an alternative to current topical antibiotic-based treatments. Promisingly, the ability of this system to release water-sensitive actives in response to shear may be useful for controlled delivery of other therapeutic molecules.


Assuntos
Antibacterianos , Bactérias/crescimento & desenvolvimento , Óleos , Parafina , Espécies Reativas de Oxigênio , Antibacterianos/química , Antibacterianos/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Emulsões , Óleos/química , Óleos/farmacologia , Parafina/química , Parafina/farmacologia , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/farmacologia
16.
Mater Sci Eng C Mater Biol Appl ; 103: 109793, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31349430

RESUMO

To gain a better understanding of neurodegeneration mechanisms and for preclinical evaluation of new therapeutics more accurate models of neuronal tissue are required. Our strategy was based on the implementation of advanced engineered system, like membrane bioreactor, in which neurons were cultured in the extracapillary space of poly(l-lactic acid) (PLLA) microtube array (MTA) membranes within a dynamic device designed to recapitulate specific microenvironment of living neuronal tissue. The high membrane permeability and the optimized fluid dynamic conditions created by PLLA-MTA membrane bioreactor provide a 3D low-shear stress environment fully controlled at molecular level with enhanced diffusion of nutrients and waste removal that successfully develops neuronal-like tissue. This neuronal membrane bioreactor was employed as in vitro model of ß-amyloid -induced toxicity associated to Alzheimer's disease, to test for the first time the potential neuroprotective effect of the isoflavone glycitein. Glycitein protected neurons from the events induced by ß-amyloid aggregation, such as the production of ROS, the activation of apoptotic markers and ensuring the viability and maintenance of cellular metabolic activity. PLLA-MTA membrane bioreactor has great potential as investigational tool in preclinical research, contributing to expand the available in vitro devices for drug screening.


Assuntos
Reatores Biológicos , Membranas Artificiais , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/toxicidade , Antioxidantes/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Isoflavonas/química , Isoflavonas/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Poliésteres/química , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/metabolismo
17.
Mater Sci Eng C Mater Biol Appl ; 103: 109797, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31349484

RESUMO

Many conventional bactericidal materials exhibit antibacterial activities by releasing biocides, which potentially trigger antibiotic resistance and cause environmental concerns. In the present work, we reported the development of antibacterial nanocomposite membrane containing upconversion nanoparticles (UCNPs) by electrospinning. The nanocomposite membrane itself was not bactericidal but exhibits strongly antimicrobial performance on demand as activated by near-infrared (NIR) light. Upon just 5 min of NIR irradiation, the UCNPs in the nanocomposite membrane could trigger the release of reactive oxygen species (ROS) from photosensitizers, which could kill both Gram-positive Staphylococcus aureus (94.5%) and Gram-negative Escherichia coli (93.2%) rapidly. Moreover, the bactericidal activity could be effectively maintained for at least four cycles. In addition, the nanocomposite membrane showed no adverse effects on the mammalian cells, as verified by a cytotoxicity assay. This work provided a new strategy in designing novel antibacterial materials that might be potentially applied in infection-resistant and wound healing.


Assuntos
Raios Infravermelhos , Membranas Artificiais , Nanopartículas/química , Fármacos Fotossensibilizantes/química , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Escherichia coli/efeitos da radiação , Azul de Metileno/química , Camundongos , Nanopartículas/toxicidade , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/farmacologia , Polivinil/química , Teoria Quântica , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus/efeitos dos fármacos
18.
Oxid Med Cell Longev ; 2019: 2930504, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31316715

RESUMO

Aquaporins (AQPs) are transmembrane proteins that conduct not only water molecules across the cell membrane but also other solutes, such as reactive oxygen and nitrogen species (RONS), produced (among others) by cold atmospheric plasma (CAP). These RONS may induce oxidative stress in the cell interior, which plays a role in cancer treatment. The underlying mechanisms of the transport of RONS across AQPs, however, still remain obscure. We apply molecular dynamics simulations to investigate the permeation of both hydrophilic (H2O2 and OH) and hydrophobic (NO2 and NO) RONS through AQP1. Our simulations show that these RONS can all penetrate across the pores of AQP1. The permeation free energy barrier of OH and NO is lower than that of H2O2 and NO2, indicating that these radicals may have easier access to the pore interior and interact with the amino acid residues of AQP1. We also study the effect of RONS-induced oxidation of both the phospholipids and AQP1 (i.e., sulfenylation of Cys191) on the transport of the above-mentioned RONS across AQP1. Both lipid and protein oxidation seem to slightly increase the free energy barrier for H2O2 and NO2 permeation, while for OH and NO, we do not observe a strong effect of oxidation. The simulation results help to gain insight in the underlying mechanisms of the noticeable rise of CAP-induced RONS in cancer cells, thereby improving our understanding on the role of AQPs in the selective anticancer capacity of CAP.


Assuntos
Aquaporinas/química , Nitrogênio/química , Oxigênio/química , Espécies Reativas de Nitrogênio/química , Espécies Reativas de Oxigênio/química , Peróxido de Hidrogênio/química , Simulação de Dinâmica Molecular
19.
Biophys Chem ; 253: 106214, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31272076

RESUMO

Cold atmospheric plasma (CAP) has attracted substantial attention in the field of medical disinfection because its main components, reactive oxygen species (ROS), have a strong destructive effect on various cell components. The cell membrane plays an important role in maintaining proper cellular function by blocking harmful substances such as ROS. In this paper, we used molecular dynamics simulations to study the behaviour of different ROS at the membrane-water interface. The results showed that the cell membrane presented a weak barrier to hydrophobic ROS (O2) but effectively prevented hydrophilic ROS (OH, HO2, H2O2) from entering the cell. The plasma treatment significantly enhanced the permeability of the cell membrane to HO2, while the energetic barrier to other types of ROS changed only slightly. O2 very likely stopped in the centre of the lipid bilayer when crossing the membrane and there attacked the unsaturated region of the phospholipid. Cholesterol was most likely oxidized by HO2, causing a condensing effect that destroyed the integrity and fluidity of the cell membrane. The study also found that large amounts of ROS decreased the thickness of the cell membrane, and the phospholipid arrangement became disordered.


Assuntos
Membrana Celular/química , Simulação de Dinâmica Molecular , Espécies Reativas de Oxigênio/química , Membrana Celular/metabolismo , Ligações de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Bicamadas Lipídicas/química , Fosfolipídeos/química , Gases em Plasma , Espécies Reativas de Oxigênio/metabolismo
20.
Environ Sci Pollut Res Int ; 26(25): 25985-25999, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31273661

RESUMO

The large-scale use of quaternary ammonium compounds (QACs) in medicines or disinfectants can lead to their release into the environment, posing a potential risk to organisms. This study examined the effects of three typical QACs, dodecyltrimethylammonium chloride (DTAC), dodecyldimethylbenzylammonium chloride (DBAC), and didodecyldimethylammonium chloride (DDAC), on hydroponically cultured wheat seedlings. After 14 days of exposure, both hormesis and phytotoxicity were observed in the wheat seedlings. The shoot and root fresh weight gradually increased as QAC concentrations rose from 0.05 to 0.8 mg L-1. However, higher QAC concentrations severely inhibited plant growth by decreasing shoot and root fresh weight, total root length, and photosynthetic pigment content. Moreover, the increase in malondialdehyde and O2.- contents, as well as root membrane permeability, reflected an oxidative burst and membrane lipid peroxidation caused by QACs. However, the effects of QACs on the levels of these oxidative stress markers were compound-specific, and the changes in superoxide dismutase, peroxidases, and catalase activity were partly related to reactive oxygen species levels. Considering the order of median effective concentration values (EC50) and the levels of oxidative stress induced by the three tested QACs, their phytotoxicities in wheat seedlings increased in the following order: DDAC < DTAC < DBAC, which mainly depended on their characteristics and applied concentrations. These results, which illustrated the complexity of QAC toxicity to plants, could potentially be used to assess the risk posed by these compounds in the environment.


Assuntos
Malondialdeído/química , Estresse Oxidativo/efeitos dos fármacos , Peroxidases/metabolismo , Peróxidos/química , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/farmacologia , Espécies Reativas de Oxigênio/química , Plântula/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Triticum/crescimento & desenvolvimento , Malondialdeído/farmacologia , Peroxidases/química , Fotossíntese/efeitos dos fármacos , Espécies Reativas de Oxigênio/farmacologia , Superóxido Dismutase/química
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