Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 812
Filtrar
1.
Ecotoxicol Environ Saf ; 200: 110747, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32460052

RESUMO

The presence of surfactants may affect the bioavailability of polycyclic aromatic hydrocarbons. A hydroponic experiment was conducted to investigate the response of Hydrocharis dubia (Bl.) Backer to different concentrations of linear alkylbenzene sulfonate (LAS), naphthalene (NAP) and their mixture (0.5, 5, 10, and 20 mg/L) for 14 days and 28 days. The results showed that LAS had a greater toxic effect on H. dubia growth than NAP at treatment concentrations of 0.5-20 mg/L. The combined effect of LAS and NAP was damaging to H. dubia at concentrations of LAS + NAP ≥5 + 5 mg/L. When LAS + NAP ≥10 + 10 mg/L, the underground parts of H. dubia suffered more significant damage than the aboveground parts. Under the treatments with LAS, NAP and their mixture, H. dubia experienced oxidative stress. Soluble proteins and antioxidant enzymes were the main substances protecting H. dubia from LAS stress, and superoxide dismutase (SOD) and peroxidase (POD) were the main protective enzymes. When exposed to NAP, H. dubia growth was stimulated and promoted at the same time. In the short-term treatment (14 d), catalase (CAT) activity was sensitive to NAP stimulation, and soluble proteins and SOD were the main protective substances produced. Soluble sugars, SOD and ascorbate peroxidase (APX) played important protective roles during the longer exposure time (28 d). The physiological response of H. dubia exposed to the combined toxicants was weaker than the response to exposure to individual toxicants. The responses of SOD and CAT activity were positive in the short term (14 d), and these were the main protective enzymes. As the exposure time increased (28 d), the plant antioxidant system responded negatively.


Assuntos
Ácidos Alcanossulfônicos/toxicidade , Hydrocharitaceae/efeitos dos fármacos , Naftalenos/toxicidade , Tensoativos/toxicidade , Ácidos Alcanossulfônicos/antagonistas & inibidores , Antioxidantes/metabolismo , Ascorbato Peroxidases/metabolismo , Catalase/metabolismo , Sinergismo Farmacológico , Hydrocharitaceae/enzimologia , Hydrocharitaceae/metabolismo , Naftalenos/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/metabolismo , Superóxido Dismutase/metabolismo
2.
Aquat Toxicol ; 224: 105480, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32417752

RESUMO

The calanoid copepod, Acartia tonsa, is relatively sensitive to marine pollution. Glutathione S-transferase (GST) multifunctional enzyme, as a biomarker, play an important role in detoxification metabolism of exogenous substances. In the present study, GST-theta and GST-mu class homology genes (designated as AtGSTT1 and AtGSTM2) were identified and characterized from A. tonsa. The coding sequence of AtGSTT1 comprised 726 bp and encoded a putative protein of 241 amino acid residues. AtGSTM2 contained an open reading frame of 678 bp that encoded a putative 227 amino acid polypeptide. Both proteins contained a conserved GST-N domain and a GST-C domain. Structural analysis revealed the characteristic N-terminal G-site. Three-dimensional structure analysis showed that AtGSTT1 and AtGSTM2 have two typical domains of GST family: The ßαßαßßα topology structure at the N- terminus and the superhelical structure at the C- terminus. Subsequently, the expression levels of the two GST genes were detected in A. tonsa using real-time quantitative PCR after exposure to 1,2-dimethylnaphthalene (C2-NAPH) at different concentrations (0.574, 5.736 and 57.358 µg/L) for 24, 48, 72, and 96 h. AtGSTT1 mRNA expression was significantly up-regulated in a time-dependent manner and the highest mRNA expression occurred at 5.736 µg/L C2-NAPH exposure for 96 h. AtGSTM2 mRNA expression peaked at 72 h in 0.574 µg/L and 5.736 µg/L dose groups. The expression level of AtGSTM2 showed an increasing trend in a time-dependent manner at 57.358 µg/L of C2-NAPH. These results suggested that GST genes may play an important role in protecting A. tonsa from C2-NAPH pollution, and provide a theoretical basis for further study on the molecular mechanism of polycyclic aromatic hydrocarbon (PAHs) pollution on zooplankton.


Assuntos
Copépodes/efeitos dos fármacos , Monitoramento Ambiental/métodos , Glutationa Transferase/genética , Naftalenos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Sequência de Bases , Clonagem Molecular , Copépodes/enzimologia , Copépodes/genética , DNA Complementar/genética , Relação Dose-Resposta a Droga , Glutationa Transferase/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , RNA Mensageiro/genética , Testes de Toxicidade Aguda
3.
Environ Pollut ; 259: 113838, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32023785

RESUMO

To date limited information's are available concerning unintentional productions, screening, profiling, and health risks of polychlorinated naphthalenes (PCNs) in ambient environment and occupational environment. Literature reveals that dust is a neglected environmental matrix never measured for PCNs. To our knowledge, this is the first study to investigate the concentrations and health risks of PCNs in indoor dust, air, and blood of major e-waste recycling hubs in Pakistan. Indoor air (n = 125), dust (n = 250), and serum (n = 250) samples were collected from five major e-waste hubs and their vicinity to measure 39 PCN congeners using GC-ECNI-MS. ∑39PCN concentrations in indoor air, dust, and serum (worker > resident > children) samples ranged from 7.0 to 9583 pg/m3, from 0.25 to 697 ng/g, and from 0.15 to 401 pg/g lipid weight, respectively. Predominant PCN congeners in indoor air and dust were tri- and tetra-CNs, while tetra- and penta-CNs were dominant in human serum samples. The higher PCNs contribution was recorded at the recycling units, while the lower was observed at the shops of the major e-waste hubs. Higher contribution of combustion origin CNs in air, dust and human samples showed combustion sources at the major e-waste hubs, while Halowax and Aroclor based technical mixture showed minor contribution in these samples. Mean toxic equivalent (TEQ) concentrations of PCNs were 2.79E+00 pg-TEQ/m3, 1.60E-02 ng-TEQ/g, 8.11E-01 pg-TEQ/g, 7.14E-01 pg-TEQ/g, and 6.37E-01 pg-TEQ/g for indoor air, dust, and serum samples from workers, residents, and children, respectively. In our study, CNs- 66/67 and -73 in indoor air, dust, and human serum were the great contributors to total TEQ concentrations of PCNs. This first base line data directs government and agencies to implement rules, regulation to avoid negative health outcomes and suggests further awareness in regard of provision of proper knowledge to the target population.


Assuntos
Resíduo Eletrônico , Exposição Ambiental , Naftalenos , Criança , Poeira , Resíduo Eletrônico/efeitos adversos , Exposição Ambiental/efeitos adversos , Monitoramento Ambiental , Humanos , Naftalenos/análise , Naftalenos/química , Naftalenos/toxicidade , Paquistão , Medição de Risco
4.
J Biochem Mol Toxicol ; 34(1): e22420, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31746523

RESUMO

Oxidative stress-induced toxicity plays a major role in ocular diseases such as retinal degeneration, age-related cataract (ARC) formation and macular dystrophy. In this study, we explored the possible role of resveratrol (RSV) at the different dose levels (10, 20 and 40 mg/kg/day, ip) in an experimental model of naphthalene (1 g/kg/day, po)-induced age-related cataracts. Morphological changes in the eyes of the rats in two groups, the RSV and the ARC groups, were monitored weekly, and biochemical parameters in the lenses were assessed after completion of the experimental work. A comparison between the rats in the two groups showed that treatments at RSV doses of 20 and 40 mg/kg/day significantly retarded lenticular opacity, restored antioxidants (CAT, SOD, GPX, GSH), Ca2+ ATPase function, and protein contents, and reduced lipid peroxidation in the lenses of the animals in the RSV group. The treatment with resveratrol at a dose of 10 mg/kg/day did not show any anti-cataractogenic effects. Based on the results of our investigation, we conclude that supplemental doses of resveratrol at 40 mg/kg/day effectively prevent cataract formation associated with the aging via increased soluble protein contents and Ca2+ homeostasis, apart from the antioxidant restoration. The results demonstrate that RSV treatment may be considered as a promising preventive or supplemental measure for delaying and/or preventing the formation of ARCs.


Assuntos
Catarata/induzido quimicamente , Catarata/prevenção & controle , Naftalenos/toxicidade , Resveratrol/farmacologia , Animais , Relação Dose-Resposta a Droga , Masculino , Ratos , Ratos Sprague-Dawley , Resveratrol/administração & dosagem
5.
Toxicol Lett ; 319: 129-137, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31730886

RESUMO

The increasing use of synthetic cannabinoids (SCBs) in recreational settings is becoming a new paradigm of drug abuse. Although SCBs effects mimic those of the Cannabis sativa plant, these drugs are frequently more potent and hazardous. It is known that endocannabinoid signalling plays a crucial role in diverse reproductive events such as placental development. Moreover, the negative impact of the phytocannabinoid Δ9-tetrahydrocannabinol (THC) in pregnancy outcome, leading to prematurity, intrauterine growth restriction and low birth weight is well recognized, which makes women of childbearing age a sensitive group to developmental adverse effects of cannabinoids. Placental trophoblast turnover relies on regulated processes of proliferation and apoptosis for normal placental development. Here, we explored the impact of the SCBs JWH-018, JWH-122 and UR-144 and of the phytocannabinoid THC in BeWo cell line, a human placental cytotrophoblast cell model. All the cannabinoids caused a significant decrease in cell viability without LDH release, though this effect was only detected for the highest concentrations of THC. Moreover, a cell cycle arrest at the G2/M phase was also observed. JWH-018 and JWH-122 increased reactive oxygen species (ROS) production and THC, UR-144 and JWH-122 caused loss of mitochondrial membrane potential. All the compounds were able to induce caspase-9 activation. The involvement of apoptotic pathways was further confirmed through the significant increase in caspase -3/-7 activities. For UR-144, this effect was reversed by the CB1 antagonist AM281, for JWH-018 and THC this effect was mediated by both cannabinoid receptors CB1 and CB2 while for JWH-122 it was cannabinoid receptor-independent. This work demonstrates that THC and SCBs are able to induce apoptotic cell death. Although they may act through different mechanisms and potencies, the studied cannabinoids have the potential to disrupt gestational fundamental events.


Assuntos
Apoptose/efeitos dos fármacos , Canabinoides/toxicidade , Dronabinol/toxicidade , Indóis/toxicidade , Naftalenos/toxicidade , Placenta/citologia , Placenta/efeitos dos fármacos , Adulto , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Feminino , Humanos , L-Lactato Desidrogenase/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Gravidez , Espécies Reativas de Oxigênio/metabolismo , Trofoblastos/efeitos dos fármacos
6.
Ecotoxicol Environ Saf ; 189: 110051, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31812022

RESUMO

Naphthalene has remained a challenge how to eradicate it from the water because of its carcinogenic risk to humans. In the present study, naphthalene prominently increased the rates of embryonic mortality and malformation, and decreased the hatchability of zebrafish which have a high developmental similarity to humans. Moreover, multiple-organ toxicity were notably found in naphthalene-treated zebrafish. Here, irradiated graphene aerogel (IGA) was successfully prepared from high-energy electron beam to generate more wrinkles, folds, defects and a strong absorption capability for naphthalene, compared with the non-irradiated graphene aerogel. IGA was outstandingly found to remove naphthalene from the embryo culture medium, and subsequently inhibit the embryotoxicity and maintain tissue integrity by restoring cardiac function, attenuating apoptosis signals, recovering eye morphology and structure, reducing expression of heat shock protein 70 in the tissues and promoting behavioral capacity. Meanwhile, no obvious negative impact of IGA was found in the developing zebrafish from embryo to larvae. Consequently, reduction in the toxicity of naphthalene during zebrafish embryogenesis was mediated by IGA as an advanced strategy.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Grafite/química , Naftalenos/análise , Poluentes Químicos da Água/análise , Peixe-Zebra , Animais , Grafite/efeitos da radiação , Grafite/toxicidade , Hidrogéis , Larva/efeitos dos fármacos , Naftalenos/toxicidade , Propriedades de Superfície , Testes de Toxicidade Aguda , Poluentes Químicos da Água/toxicidade
7.
Chemosphere ; 244: 125448, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31812059

RESUMO

Here, we characterized the dioxin-like activities of 42 polychlorinated naphthalenes (PCNs) and 6 technical Halowax formulations by using the DR-CALUX (dioxin-responsive chemically activated luciferase expression) assay with rat hepatoma luciferase-expressing H4IIE cells. Of the 42 PCNs examined, 31 showed dioxin-like activities, for which the mass-based REP-EC5TCDD (potency relative to that of 2,3,7,8-tetrachlorodibenzo-p-dioxin based on the 5% effective concentration determined from the dose-response curve for 2,3,7,8-TCDD) ranged from 0.00000012 to 0.0051, indicating that some of the PCNs (e.g., 1,2,3,6,7,8-HxCN and 1,2,3,4,6,7-HxCN) had dioxin-like activities that were equal to or higher than the WHO-TEFs and the mass-based REP-EC5TCDD reported for dioxins such as octachlorodibenzo-p-dioxin, octachlorodibenzofuran, 3,3',4,4'-tetrachlorobiphenyl (PCB-77), 3,4,4',5-tetrachlorobiphenyl (PCB-81), and 3,3',4,4',5,5'-hexachlorobiphenyl (PCB-169). For PeCNs to OCN with high dioxin-like activities, REPs determined in previous studies were comparable to the REP values obtained in the present study. The TCDD-EQs (2,3,7,8-TCDD equivalents) obtained experimentally for the Halowax formulations decreased in the order HW1051 (37 mg/kg) > HW1014 (30 mg/kg) > HW1013 (5.6 mg/kg) > HW1099 (2.9 mg/kg) > HW1001 (0.60 mg/kg) > HW1031 (<0.10 mg/kg) and were comparable to the theoretical TCDD-EQs calculated by multiplying the concentration and REP of each PCN. In addition, the theoretical TCDD-EQs for PCNs in emission gases produced by thermal processes were below the Japanese emission standard of 0.1-10 ng WHO-toxicity equivalent (TEQ)/m3N, and 3 to 4 orders of magnitude lower than the corresponding WHO-TEQ. Based on a comparison of theoretical and experimental TCDD-EQs, we found that our REP-based approach was suitable for the risk management of industrially produced and unintentionally generated dioxin-like PCNs. This approach will be particularly useful for the risk management of unintentionally generated PCNs in emission gases because the contribution of dioxin-like PCNs to the whole dioxin-like toxicity of emission gases can be elucidated.


Assuntos
Dioxinas/toxicidade , Poluentes Ambientais/toxicidade , Naftalenos/toxicidade , Animais , Benzofuranos , Bioensaio , Luciferases/metabolismo , Bifenilos Policlorados , Dibenzodioxinas Policloradas , Ratos , Gestão de Riscos , Testes de Toxicidade
8.
Eur J Med Chem ; 188: 111986, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31884407

RESUMO

Breast cancer is the second leading cause of deaths in women globally. Present communication deals with design and synthesis of a few diarylnaphthyls as possible anti-breast cancer agents. Among the thirty three representatives with significant antiproliferative activity compounds 23 and 50 were quite efficacious against human breast cancer cells. Compound 50 induced apoptosis in both MCF-7 and MDA-MB-231 cells and exerted S phase and G2/M phase arrest respectively via distinct mechanistic pathways. It showed moderate microtubule destabilization. Further, it exhibited DNA topoisomerase-II inhibition effect in MCF-7 cells. It was well tolerable and found safe up to 300 mg/kg dose in Swiss albino mice. The dual action antiproliferative effect of compound 50 is quite interesting and warrants for future development.


Assuntos
Antineoplásicos/farmacologia , Naftalenos/farmacologia , Pirrolidinas/farmacologia , Inibidores da Topoisomerase II/farmacologia , Moduladores de Tubulina/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/toxicidade , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Masculino , Camundongos , Simulação de Acoplamento Molecular , Naftalenos/síntese química , Naftalenos/toxicidade , Pirrolidinas/síntese química , Pirrolidinas/toxicidade , Inibidores da Topoisomerase II/síntese química , Inibidores da Topoisomerase II/toxicidade , Moduladores de Tubulina/síntese química , Moduladores de Tubulina/toxicidade
9.
Environ Int ; 136: 105436, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31887713

RESUMO

Polychlorinated naphthalenes are teratogenic environmental contaminants. Mother milk is the most important food for nursing infants. The World Health Organization actively promotes breastfeeding for its immunological, psychological, and economic advantages. We firstly measured concentrations of polychlorinated naphthalenes in human milk from 19 provinces in China and estimated their potential health risks to nursing infants and their possible sources. Concentrations ranged from 211.07 to 2497.43 pg/g lipid. The high prevalence of highly toxic hexachlorinated naphthalenes (Hexa-CN66/67) in human milk samples indicated a higher health risk in the sampling areas. Cancer risk posed to nursing infants was not significant, but potential non-carcinogenic adverse health effects were suggested and should be emphasized in some sampling areas. Unintentional emission of polychlorinated naphthalenes from industries that employ thermal processes appears to be the main source for PCNs in human milk in most sampling areas. Correlation analysis also suggested PCNs as impurities in polychlorinated biphenyl mixtures as a previously unrecognized source of polychlorinated naphthalenes in human milk.


Assuntos
Leite Humano , Naftalenos , Bifenilos Policlorados , China , Dibenzofuranos Policlorados , Monitoramento Ambiental , Humanos , Lactente , Leite Humano/química , Naftalenos/toxicidade , Bifenilos Policlorados/toxicidade , Medição de Risco
10.
Anal Chim Acta ; 1095: 154-161, 2020 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-31864617

RESUMO

A latent turn-on fluorescent probe for the detection of malononitrile (NCCH2CN), a precursor of hydrogen cyanide (HCN) in the mammalian tissue metabolism, is developed based on reaction-based fluorophore generation for the first time. Malononitrile is utilized within a wide spectrum of academic and industrial applications, and it is a key reagent to make o-chlorobenzylidene malononitrile (CS gas; tear gas), which is used for riot control. Due to its extensive use as well as potential health risks and the environmental pollution, malononitrile monitoring method has been required. In this paper, we discovered that our key sensing platform, 6-(dimethylamino)-3-hydroxy-2-naphthaldehyde (named Mal-P1), responds sensitively and selectively towards malononitrile. The Knoevenagel condensation induced benzo [g]coumarin formation of Mal-P1 with malononitrile showed significant fluorescence turn-on response. In addition, Mal-P1 showed the malononitrile sensing ability in environmental samples (real water, CS gas) and imaging ability in biological sample (HeLa cell line) using fluorescence microscopy with low cytotoxicity. The successful demonstrations will facilitate further applications in a variety of fields.


Assuntos
Aldeídos/química , Corantes Fluorescentes/química , Naftalenos/química , Nitrilos/análise , Poluentes Químicos da Água/análise , Aldeídos/síntese química , Aldeídos/toxicidade , Água Potável/análise , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Células HeLa , Humanos , Lagos/análise , Limite de Detecção , Microscopia Confocal , Microscopia de Fluorescência , Naftalenos/síntese química , Naftalenos/toxicidade , Nitrilos/química , Rios/química , Água do Mar/análise , Espectrometria de Fluorescência , Poluentes Químicos da Água/química , o-Clorobenzilidenomalonitrila/síntese química
11.
Analyst ; 144(23): 6922-6927, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31660553

RESUMO

Formaldehyde (FA), as a reactive carbonyl species, is endogenously generated in various biological processes. Abnormal levels of FA could lead to various cellular dysfunction and pathological conditions. Here, we develop a new activatable fluorescent probe for highly selective visualization of FA in living cells. Our probe (Naph-1) is designed using a naphthalene derivative as the fluorophore and hydrazone as a recognition site for FA. Naph-1 is essentially nonemissive. After reacting with FA, the amine moiety is converted into a Schiff base with electron-withdrawing ability and the fluorescence is simultaneously turned on due to synergetic intramolecular charge transfer and favoured excited state intramolecular proton transfer effects. Naph-1 exhibits a large Stokes shift upon reaction with FA. Furthermore, it possesses high selectivity and superior sensitivity toward FA with an estimated limit of detection of 0.35 µM. Moreover, Naph-1 is also successfully applied to image both endogenous and exogenous formaldehyde in living cells. These features demonstrate that Naph-1 holds great potential in the detection and imaging of formaldehyde in biological systems.


Assuntos
Corantes Fluorescentes/química , Formaldeído/análise , Hidrazonas/química , Naftalenos/química , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Formaldeído/química , Células HeLa , Humanos , Hidrazonas/síntese química , Hidrazonas/toxicidade , Limite de Detecção , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Naftalenos/síntese química , Naftalenos/toxicidade
12.
Ecotoxicol Environ Saf ; 185: 109707, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31561078

RESUMO

Effective biodegradation of hydrophobic pollutants, such as 1-chloronaphthalene, is strictly associated with the adaptation of environmental bacteria to their assimilation. This study explores the relation between the modifications of cell properties of bacteria belonging to Pseudomonas and Serratia genera resulting from a 12-month exposure to 1-chloronaphthalene, and their biodegradation efficiency. In the presented study, both bacterial strains exhibited higher (70%) degradation of this compound after exposure compared to unexposed (55%) systems. This adaptation can be associated with increased ratio of polysaccharides in the outer layers of bacterial cells, which was confirmed using infrared spectroscopy analysis. Additionally, the analysis of Raman spectra indicated conformational changes of extracellular carbohydrates from α- to ß-anomeric structure. Moreover, the changes in the cell surface hydrophobicity and cell membrane permeability differed between the strains and the Pseudomonas strain exhibited more significant modifications of these parameters. The results suggest that adaptation strategies of both tested strains are different and involve diverse reconstructions of the cell wall and membranes. The results provide a novel and deep insight into the interactions between environmental bacterial strains and chloroaromatic compounds, which opens new perspectives for applying spectrometric methods in investigation of cell adaptation strategies as a result of long-term contact with toxic pollutants.


Assuntos
Aclimatação/efeitos dos fármacos , Poluentes Ambientais/análise , Naftalenos/análise , Pseudomonas/efeitos dos fármacos , Serratia/efeitos dos fármacos , Biodegradação Ambiental , Poluentes Ambientais/toxicidade , Interações Hidrofóbicas e Hidrofílicas , Naftalenos/toxicidade , Polissacarídeos Bacterianos/metabolismo , Pseudomonas/metabolismo , Serratia/metabolismo
13.
Am J Physiol Lung Cell Mol Physiol ; 317(5): L602-L614, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31461302

RESUMO

Chronic obstructive pulmonary disease (COPD) is a life-threatening lung disease. Although cigarette smoke was considered the main cause of development, the heterogeneous nature of the disease leaves it unclear whether other factors contribute to the predisposition or impaired regeneration response observed. Recently, epigenetic modification has emerged to be a key player in the pathogenesis of COPD. The addition of methyl groups to arginine residues in both histone and nonhistone proteins by protein arginine methyltransferases (PRMTs) is an important posttranslational epigenetic modification event regulating cellular proliferation, differentiation, apoptosis, and senescence. Here, we hypothesize that coactivator-associated arginine methyltransferase-1 (CARM1) regulates airway epithelial cell injury in COPD pathogenesis by controlling cellular senescence. Using the naphthalene (NA)-induced mouse model of airway epithelial damage, we demonstrate that loss of CC10-positive club cells is accompanied by a reduction in CARM1-expressing cells of the airway epithelium. Furthermore, Carm1 haploinsuffficent mice showed perturbed club cell regeneration following NA treatment. In addition, CARM1 reduction led to decreased numbers of antisenescent sirtuin 1-expressing cells accompanied by higher p21, p16, and ß-galactosidase-positive senescent cells in the mouse airway following NA treatment. Importantly, CARM1-silenced human bronchial epithelial cells showed impaired wound healing and higher ß-galactosidase activity. These results demonstrate that CARM1 contributes to airway repair and regeneration by regulating airway epithelial cell senescence.


Assuntos
Senescência Celular , Células Epiteliais/patologia , Proteína-Arginina N-Metiltransferases/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Mucosa Respiratória/patologia , Cicatrização , Idoso , Animais , Apoptose , Diferenciação Celular , Proliferação de Células , Células Epiteliais/metabolismo , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Naftalenos/toxicidade , Doença Pulmonar Obstrutiva Crônica/metabolismo , Mucosa Respiratória/metabolismo
14.
Talanta ; 204: 762-768, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31357363

RESUMO

Herein we reported a two-photon (TP) fluorescence "turn-on" probe MNPO, exhibiting high selectivity and sensitivity towards intracellular cysteine (Cys) with excellent lysosomal localization. The probe displayed fast response towards Cys over homocysteine (Hcy), glutathione (GSH), and other various analytes under physiological conditions. Low cytotoxicity made it successful for TP imaging of Cys in HeLa cells with an ultralow probe concentration of 250 nM, and a rapid response of only 10 min. Simultaneously, colocalization experiments in lysosome demonstrated its ability for specific in situ detection of lysosomal Cys in living cells, which shed light on its potential applications in biomedical applications. Beyond that MNPO was successfully applied for TP imaging of Cys in mice organ tissues such as heart, liver, and spleen, and the penetration depth of mice heart tissue was up to 184 µm, which disclosed the predominant TP characteristic. We believe that this study will provide some useful information toward diagnosis and treatment of pathogenesis associated with Cys or lysosomes in future.


Assuntos
Cisteína/análise , Corantes Fluorescentes/química , Lisossomos/metabolismo , Alcenos/síntese química , Alcenos/química , Alcenos/toxicidade , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Células HeLa , Humanos , Limite de Detecção , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Naftalenos/síntese química , Naftalenos/química , Naftalenos/toxicidade , Fótons
15.
Talanta ; 203: 90-98, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31202355

RESUMO

In this work, we designed a kind of novel fluorescent probes based on naphthalene-benzoindole conjugate derived for sensitively monitoring the pH fluctuation in environment and biological systems. In the spectral method, these two probes both show significant red shift, color change and fluorescence quenching due to the effect of intramolecular charge transfer (ICT) mechanism. Moreover, we found that the probe bearing with carboxyl group displayed a more hydrophilicity than the one bearing with hydrogen atom instead, and the former exhibits a faster response and higher fluorescence intensity. Besides, the probe bearing with carboxyl group shows lower cytotoxicity, evidences by the vitro study. It indicates that this probe has great potential in application in living cell imaging as well as pH-fluctuation monitoring.


Assuntos
Corantes Fluorescentes/química , Indóis/química , Naftalenos/química , Animais , Linhagem Celular Tumoral , Colorimetria/métodos , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Humanos , Concentração de Íons de Hidrogênio , Indóis/síntese química , Indóis/toxicidade , Camundongos , Microscopia de Fluorescência/métodos , Modelos Químicos , Naftalenos/síntese química , Naftalenos/toxicidade
16.
Neuropharmacology ; 155: 10-21, 2019 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-31103616

RESUMO

Patients under cannabis-based therapies are usually chronically exposed to cannabinoids. Chronic treatment with a cannabinoid receptor agonist, WIN 55,212-2, affects brain metabolism and modifies functional connectivity between brain areas responsible for memory and learning. Therefore, it is of uttermost importance to discover strategies to mitigate the negative side-effects of cannabinoid-based therapies. Previously, we showed that a single treatment with the synthetic cannabinoid WIN 55,212-2 disrupts recognition memory, an effect mediated by cannabinoid receptor 1 (CB1R) and cancelled by concomitant administration of adenosine A2A receptor (A2AR) antagonists. We herein evaluate if memory deficits induced by chronic exposure to WIN 55,212-2 can also be reverted by A2AR antagonism, and assessed the synaptic mechanisms that could be involved in that reversal. We show that chronic administration of KW-6002 (istradefylline) (3 mg/kg/28days) reverts memory deficits (evaluated through the Novel Object Recognition Test) induced by chronic cannabinoid exposure (WIN 55,212-2, 1 mg/kg/28 days). Long Term Potentiation (LTP) of synaptic potentials recorded from the CA1 area of the hippocampus was impaired by WIN 55,212-2 (300 nM), an effect partially rescued by the A2AR antagonist, SCH 58261 (100 nM). Chronic administration of KW-6002 or WIN 55,212-2 did not affect A2AR or CB1R binding in the hippocampus and in the prefrontal cortex. These results, showing that A2AR antagonism can still revert memory deficits after chronic administration of a cannabinoid, an effect that involves mitigation of synaptic plasticity impairment, strongly indicate that adenosine A2ARs are appropriate targets to tackle side-effects of putative therapies involving the activation of cannabinoid receptors.


Assuntos
Antagonistas do Receptor A2 de Adenosina/uso terapêutico , Canabinoides/toxicidade , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/prevenção & controle , Receptor A2A de Adenosina , Antagonistas do Receptor A2 de Adenosina/farmacologia , Animais , Benzoxazinas/toxicidade , Masculino , Transtornos da Memória/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Morfolinas/toxicidade , Naftalenos/toxicidade , Purinas/farmacologia , Purinas/uso terapêutico , Receptor A2A de Adenosina/metabolismo
17.
Pediatrics ; 143(6)2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31064798

RESUMO

Naphthalene poisoning due to exposure to mothballs is a common cause of toxicity in children worldwide. Naphthalene toxicity is known to cause hemolytic anemia, methemoglobinemia, and hepatic and renal injury. Neonates are more susceptible to the effects of oxidative stress from naphthalene because of their low glutathione stores and immaturity of hepatic enzymes. However, there are no reported cases of chronic fetal exposure to naphthalene during pregnancy. We report a novel case of chronic fetal exposure to naphthalene-containing mothballs that occurred from the second trimester through the third trimester of pregnancy. Our patient presented with hyperbilirubinemia, requiring exchange transfusion, severe hemolytic anemia, pulmonary hypertension, respiratory failure, and renal failure and progressed to develop "bronze baby" syndrome. Pregnant mothers should be diligently screened for such exposures and if found should receive psychiatric evaluation and counseling to prevent such devastating effects in neonates.


Assuntos
Ingestão de Alimentos , Naftalenos/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Adulto , Anemia Hemolítica/sangue , Anemia Hemolítica/induzido quimicamente , Anemia Hemolítica/diagnóstico , Ingestão de Alimentos/fisiologia , Feminino , Humanos , Hiperbilirrubinemia/sangue , Hiperbilirrubinemia/induzido quimicamente , Hiperbilirrubinemia/diagnóstico , Recém-Nascido , Masculino , Naftalenos/administração & dosagem , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue
18.
Sci Total Environ ; 682: 151-159, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31112816

RESUMO

Napropamide is a chiral acetamide herbicide commonly applied to control Echinochloa crus-galli in maize. The inhibition effect may be enantioselective for Echinochloa crus-galli and maize. It may also be affected by the potential allelopathy at field condition. To investigate this, we have examined the inhibition effect of napropamide on Echinochloa crus-galli mono-cultured or co-cultured with maize at field conditions. Our results on morphology, physiology, chlorophyll content and chlorophyll fluorescence suggest that R-napropamide has stronger inhibitory effect than Rac-napropamide and S-napropamide on Echinochloa crus-galli, while none of them affects maize. We found that both glutathione-S-transferase (GST) genes and oxidative enzymes (superoxide dismutase, malondialdehyde) played roles in the inhibition. Accumulations of napropamide in Echinochloa crus-galli were more prominent in roots than in shoots, and no enantioselectivity was found in medium dissipation. We have observed relative allelopathy when applying napropamide to Echinochloa crus-galli co-cultured with maize. The results warrant further field studies on the enantioselectivity and allelopathy of herbicides.


Assuntos
Alelopatia/fisiologia , Echinochloa/efeitos dos fármacos , Herbicidas/farmacologia , Naftalenos/farmacologia , Zea mays/efeitos dos fármacos , Echinochloa/anatomia & histologia , Echinochloa/genética , Echinochloa/fisiologia , Herbicidas/toxicidade , Naftalenos/toxicidade , Estereoisomerismo , Zea mays/anatomia & histologia , Zea mays/genética , Zea mays/fisiologia
19.
Microbiologyopen ; 8(9): e00855, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31119875

RESUMO

In this study, we compared the expression of CYP153, sodA, sodC, and recA genes and ROS generation in hydrocarbon-degrading Rhodococcus erythropolis in the presence of cyclohexane, naphthalene, and diesel fuel. The expression of cytochrome P450, sodA (encoding Fe/Mn superoxide dismutase), recA, and superoxide anion radical generation rate increased after the addition of all studied hydrocarbons. The peak of CYP153, sodA, and recA gene expression was registered in the presence of naphthalene. The same substrate upregulated the Cu/Zn superoxide dismutase gene, sodC. Cyclohexane generated the highest level of superoxide anion radical production. Hydrogen peroxide accumulated in the medium enriched with diesel fuel. Taken together, hydrocarbon biotransformation leads to oxidative stress and upregulation of antioxidant enzymes and CYP153 genes, and increases DNA reparation levels in R. erythropolis cells.


Assuntos
Cicloexanos/toxicidade , Gasolina/toxicidade , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Naftalenos/toxicidade , Estresse Oxidativo , Rhodococcus/efeitos dos fármacos , Rhodococcus/metabolismo , Proteínas de Bactérias/biossíntese , Proteínas de Bactérias/genética , Biotransformação , Cicloexanos/metabolismo , Perfilação da Expressão Gênica , Naftalenos/metabolismo , Espécies Reativas de Oxigênio/análise
20.
Chemosphere ; 228: 577-585, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31075638

RESUMO

Although Persistent Organic Pollutants (POPs) are some of the most dangerous environmental toxicants, data on their impact on hemostasis are virtually limited. 1,2,3,5,6,7-hexachloronaphthalene (PCN67) seems to be one of the most toxic congeners of polychlorinated naphthalenes (PCNs), which have recently been listed as POPs. The toxic effects of PCNs are similar to other chlorinated aromatics, e.g. polychlorinated dibenzo-p-dioxins (PCDDs), so an impact on hemostasis could not be excluded. Therefore, this study examines, for the first time, if short-term (two and four weeks) exposure of a mixture of hexachloronaphthalene congeners with a PCN67 as a predominant component to female Wistar rats may have an impact on selected hemostasis parameters, such as overall potential and kinetic parameters of clot formation and fibrinolysis; hematology and basic coagulology parameters. It also examines the influence of PCN67 on the stability of erythrocyte membranes. Obtained results indicate that PCN67 may be an important disturbing factor regarding both coagulation and fibrinolysis processes, as well as platelet count. Exposure to PCN67 significantly affected clot formation and lysis processes and diminished fibrinogen concentration after both administration periods. After two weeks of administration, an increased activated partial thromboplastin time (APTT) was noted; after four weeks - decreased platelet count with concomitant increased in mean platelet volume. Moreover, PCN67 may exert adverse effects on the red blood cells membrane stability, which were manifested by a statistically significant increase of red blood cells lysis.


Assuntos
Hemostasia/efeitos dos fármacos , Naftalenos/toxicidade , Projetos Piloto , Animais , Poluentes Ambientais/análise , Poluentes Ambientais/toxicidade , Membrana Eritrocítica/efeitos dos fármacos , Feminino , Hemólise/efeitos dos fármacos , Tempo de Tromboplastina Parcial , Contagem de Plaquetas , Dibenzodioxinas Policloradas , Ratos , Ratos Wistar
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA