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1.
Artigo em Chinês | MEDLINE | ID: mdl-31495106

RESUMO

Objective: To study the effect of particulate matter 2.5 (PM(2.5)) on oncogene expression in human bronchial epithelial (HBE) cells. Methods: HBE cells were selected as the study subjects, and PM(2.5) treatment group (10 µg/ml and 50 µg/ml) , negative control group and positive control group (10 µmol/L Cr(6+)) were set. CCK8 assay was used to test the IC(50) value of PM(2.5). HBE cells were treated with PM(2.5) for 24 h at 10 µg/ml and 50 µg/ml, additionally, cells were treated with blank as negative control, 10 µmol/L Cr(6+) as a positive control for 24 h. After the treatment, mRNA expression of oncogenes including c-myc, c-fos, k-ras and p53 were detected by fluorescent quantitative RT-PCR, the protein expression of oncogenes were detected with western blot. Results: The IC(50) value of PM(2.5) in HBE cells is 70.12 µg/ml. The qRT-PCR data showed that compared with the control group, the expression level of c-myc gene increased by respectively 500.1%、780.7%、305.3% after exposure to 10、50 µg/ml PM(2.5) and positive control group; c-fos gene increased respectively 34.0%、76.7%、131.3% after exposure to 10、50 µg/ml PM(2.5) and positive control group; k-ras gene increased respectively 50.3%、107.0%、49.7% after exposure to 10、50 µg/ml PM(2.5) and positive control group; p53 gene decreased by 28.3%、28.7%、59.7% after exposure to 10、50 µg/ml PM(2.5) and positive control group. The western blot results showed that compared with the control group, c-myc protein increased respectively 29.7%、77.3% after exposure to 50 µg/ml PM(2.5) and positive control group; c-fos protein increased respectively 200.3%、137.0% after exposure to 50 µg/ml PM(2.5) and positive control group; k-ras protein increased respectively 106.3%、130.3%、116.7% after exposure to 10、50 µg/ml PM(2.5) and positive control group; p53 protein decreased by 43.7%、53.3%、52.1% after exposure to 10、50 µg/ml PM(2.5) and positive control group. Conclusion: PM(2.5) could promote the expression of oncogenes in HBE cells, the carcinogenicity of haze might be related to promotion of oncogenes expression induced by PM(2.5).


Assuntos
Células Epiteliais/efeitos dos fármacos , Oncogenes , Material Particulado/toxicidade , Brônquios/citologia , Células Cultivadas , Humanos , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína Supressora de Tumor p53/genética
2.
Toxicol Lett ; 316: 27-34, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31513887

RESUMO

OBJECTIVE: Atherosclerosis is an autoimmune inflammatory disease that is closely associated with long-term exposure to fine particulate matter (PM2.5). CD4+CD25+Foxp3+ regulatory T cells (Tregs) play a critical role in the regulation of T cell-mediated immune responses, and the depletion of CD4+CD25+Foxp3+ Tregs has been thought to play a prominent role in atherosclerosis. Therefore, we investigated the association between the CD4+CD25+Foxp3+ Tregs population and atherosclerotic development in ApoE-/- mice exposed to PM2.5. METHODS: We employed a real-world system to subject 40 ApoE-/- mice to ambient inhalation of PM2.5 (PM2.5 group, n = 20) or filtered air (FA group, n = 20) for 12 weeks. PM2.5 source apportionment, atherosclerotic lesions within aorta, lipid deposition and plaque accumulation in whole artery, serum level of inflammatory factors and lipid profiles, CD4+CD25+Foxp3+ Tregs population in splenocytes, Foxp3 protein and mRNA expressions in descending aorta and spleen were quantified, respectively. RESULTS: The daily average concentration of PM2.5 was 57.4 ± 25.6 µg/m3. Atherosclerotic lesions within aorta, lipid deposition and plaque accumulation in whole artery, serum levels of IL-6, TNF-α, TC and LDL-C in the PM2.5 group increased significantly compared to the FA group. Whereas, serum levels of IL-10 and TGF-ß, CD4+CD25+Foxp3+ Tregs population in splenocytes, Foxp3 protein and mRNA expressions in descending aorta and spleen in the PM2.5 group decreased significantly compared to the FA group. CONCLUSION: These results suggest that PM2.5 could accelerate the development of atherosclerosis in ApoE-/- mice, which is related to CD4+CD25+Foxp3+ Tregs down-regulation, as well as lipid deposition and systemic inflammation.


Assuntos
Aorta/efeitos dos fármacos , Doenças da Aorta/induzido quimicamente , Aterosclerose/induzido quimicamente , Fatores de Transcrição Forkhead/metabolismo , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Material Particulado/toxicidade , Linfócitos T Reguladores/efeitos dos fármacos , Animais , Aorta/imunologia , Aorta/metabolismo , Aorta/patologia , Doenças da Aorta/sangue , Doenças da Aorta/imunologia , Doenças da Aorta/patologia , Aterosclerose/sangue , Aterosclerose/imunologia , Aterosclerose/patologia , Biomarcadores/sangue , LDL-Colesterol/sangue , Citocinas/sangue , Modelos Animais de Doenças , Progressão da Doença , Fatores de Transcrição Forkhead/imunologia , Predisposição Genética para Doença , Mediadores da Inflamação/sangue , Subunidade alfa de Receptor de Interleucina-2/imunologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Tamanho da Partícula , Fenótipo , Placa Aterosclerótica , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Linfócitos T Reguladores/patologia , Fatores de Tempo
3.
Toxicol Lett ; 316: 49-59, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31520698

RESUMO

Epidemiological studies have established the correlations between PM2.5 and a wide variety of pulmonary diseases. However, their underlying pathogeneses have not been clearly elucidated yet. In the present study, the epithelial-mesenchymal transition (EMT) phenotype with enhanced proliferation and migration activity of human pulmonary epithelial cell line BEAS-2B was observed after exposure to low dose PM2.5 exposure (50 µg/ml) for 30 passages. Then, epithelial cells derived-exosomal micro-RNA (miRNA) and intracellular total RNA were extracted, and the differentially expressed exosomal miRNAs (DE-Exo-MiRs) as well as differentially expressed protein coding genes (DEGs) were identified by RNA sequencing (RNA-seq) and transcriptome analysis. We found that chronic PM2.5 exposure stimulated the release of pulmonary epithelium derived exosomes. 45 DE-Exo-MiRs including 32 novelly predicted miRNAs and 843 DEGs between PM2.5 exposed group and the normal control were detected. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that DEGs were significantly enriched in extracellular matrix organization, focal adhesion and cancer related terms. Besides, the enrichment analyses on 7774 mRNA targets of 27 DE-Exo-MiRs predicted by MiRanda software also revealed the potential regulatory role of exosomal miRNAs in pathways in cancer, Wingless/Integrated (Wnt) signaling pathway, focal adhesion related genes and other multiple pathogenic pathways. Moreover, the interactive exosomal miRNA-mRNA pair networks were constructed using Cytoscape software. Our results provided a novel basis for a better understanding of the mechanisms of chronic PM2.5 exposure induced pulmonary disorders including pulmonary fibrosis and cancer, in which exosomal miRNAs (Exo-MiRs) potentially functions by dynamically regulating gene expressions.


Assuntos
Células Epiteliais/efeitos dos fármacos , Exossomos/efeitos dos fármacos , Perfilação da Expressão Gênica/métodos , Pulmão/efeitos dos fármacos , MicroRNAs/genética , Material Particulado/toxicidade , RNA Mensageiro/genética , Transcriptoma/efeitos dos fármacos , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Biologia Computacional , Bases de Dados Genéticas , Células Epiteliais/metabolismo , Células Epiteliais/ultraestrutura , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Exossomos/genética , Exossomos/metabolismo , Exossomos/patologia , Redes Reguladoras de Genes , Humanos , Pulmão/metabolismo , Pulmão/ultraestrutura , MicroRNAs/metabolismo , Tamanho da Partícula , RNA Mensageiro/metabolismo , Medição de Risco , Fatores de Tempo , Testes de Toxicidade Crônica
4.
Toxicol Lett ; 316: 147-153, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31520700

RESUMO

Asthma is a common chronic inflammatory disease which severely reduces the quality of life in patients. Studies have demonstrated that both PM2.5 and cold stress contribute to the development of asthma. However, the combined effects of these two risking factors are unknown. In this study, we investigated the combined effects of PM2.5 exposure and cold stress (PMCS) on asthma, as well as the underlying mechanisms by using a murine model. After different exposures, the immune-pathological changes and redox states in groups were evaluated. Besides, the balance of TH1/TH2 cells and the acetylation levels of H3K9 and H3K14 in IL-4 gene promotor were detected. Our results showed that, compared with other exposures, PMCS led to an increased inflammation and redox levels in mice. It also significantly increased the percentage of TH2 T cells, which was correlated with hyperacetylation of H3K9 and H3K14 in IL-4 gene promoter in CD4+T cells. Furthermore, a significantly increased P300 and decreased HDAC1 were detected in CD4 + T cells in PMCS group. In conclusion, our findings demonstrated that PMCS exacerbated asthma in mice by increasing H3K9 and H3K14 acetylation in IL-4 gene promoter in CD4 + T cells, and P300 and HDAC1 might contribute to their combined effects.


Assuntos
Asma/induzido quimicamente , Temperatura Baixa/efeitos adversos , Histonas/metabolismo , Interleucina-4/metabolismo , Pulmão/efeitos dos fármacos , Material Particulado/toxicidade , Regiões Promotoras Genéticas , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Acetilação , Animais , Asma/genética , Asma/imunologia , Asma/metabolismo , Modelos Animais de Doenças , Proteína p300 Associada a E1A/metabolismo , Histona Desacetilase 1/metabolismo , Interleucina-4/genética , Interleucina-4/imunologia , Pulmão/imunologia , Pulmão/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Ovalbumina , Tamanho da Partícula , Processamento de Proteína Pós-Traducional , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Auxiliares-Indutores/metabolismo
5.
Toxicol Lett ; 316: 119-126, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31539570

RESUMO

In vivo experiments are still widely used for the testing of lung toxicity but there is an ethical and legal obligation to replace, reduce and refine animal testing. Lung A549 cells could serve as an in vitro indicator for acute lung toxicity but little data about the correlation of the cytotoxicity in A549 cells and data leading to CLP classifications are available. We exposed A549 cells to 19 CLP-classified substances with doses of 25, 50, and 100 µg/cm2 either under submerged (SME) condition or with aerosols at the air-liquid interface (ALIF) and determined accuracy, precision, sensitivity and the F1 score with the CLP classifications H330, H332, or H335. When data from both exposure methods were combined, we found accuracies of 0.84 ±â€¯0.05, precisions of 0.74 ±â€¯0.1, sensitivities of 0.93 ±â€¯0.08 and F1 scores of 0.82 ±â€¯0.04. Separated from each other, ALIF exposure was more sensitive at any dose but, at higher doses, also less accurate and precise compared to SME. Considering the 19 substances tested, our data suggest that cytotoxicity in A549 cells could be a reliable in vitro indicator for in vivo toxicity. Thus, we discuss how A549 could be integrated into validation test guidelines.


Assuntos
Lesão Pulmonar Aguda/induzido quimicamente , Alternativas aos Testes com Animais/métodos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Neoplasias Pulmonares/patologia , Material Particulado/toxicidade , Células A549 , Animais , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Humanos , Camundongos , Tamanho da Partícula , Pós , Reprodutibilidade dos Testes , Medição de Risco
6.
Toxicol Lett ; 315: 47-54, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31449845

RESUMO

Particulate matter with a diameter of less than 2.5 µm (PM2.5) easily deposits on lung alveoli and degrades human health. Surfactant protein A (SP-A) is the most abundant pulmonary surfactant protein stored in lamellar bodies (LBs) of alveolar epithelial type II cells. The impacts of PM2.5 on SP-A are multifaceted and intractable, and the underlying mechanism remains unclear. In this study, the expression and distribution of SP-A in Balb/c mice and A549 cells under PM2.5 exposure were investigated. The results showed that the low and medium concentration of PM2.5 gradually enhanced SP-A protein and mRNA expression, whereas the high concentration of PM2.5 conspicuously decreased SP-A protein but not its mRNA compared with the control. The trafficking of SP-A to LBs was gradually disturbed, and concomitantly, the lesions of LBs responsible for the transport and storage of SP-A protein were exacerbated with increased PM2.5 concentration. Reactive oxygen species production abundantly increased upon PM2.5 exposure, and it was antagonized by the oxidant inhibitor N-acetylcysteine. Subsequently, the injured LBs and the decrease in SP-A expression under exposure to the high concentration of PM2.5 were well rescued. The present study provides a new perspective to investigate the adverse effects of PM2.5 or diesel exhaust particles on other proteins transported to and stored in LBs.


Assuntos
Células Epiteliais Alveolares/metabolismo , Material Particulado/toxicidade , Alvéolos Pulmonares/fisiopatologia , Proteína A Associada a Surfactante Pulmonar/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Emissões de Veículos/toxicidade , Animais , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Tamanho da Partícula
7.
Artigo em Japonês | MEDLINE | ID: mdl-31434811

RESUMO

Recently, the main air pollutant has been fine particulate matter (PM2.5), which is taken up by the whole body with severe adverse health effects. The main chemical components of PM2.5 are salts of sulfate (and nitrate) and carbons. However, it remains unknown which components are toxic. Here, the author reviewed the literatures to determine which components are toxic and the main mechanisms underlying their toxicity. Many epidemiological studies have shown that sulfate concentration is strongly related to mortality. However, there is no experimental evidence showing that sulfate at environmental concentrations of PM2.5 causes cardiovascular disease or other disease. On the other hand, carbon components such as elementary carbon (EC) produces high concentrations of reactive oxygen species (ROS) via its phagocytosis by macrophages, and organic carbon (OC) also produces high concentrations of ROS during its metabolic processes, and the ROS cause acute and chronic inflammation. They cause many diseases including cardiovascular disease, asthma and cancer. Furthermore, there are many lines of evidence showing that epigenetic changes such as DNA methylation or microRNA expression induced by particulate matters also induce the development of many diseases such as those mentioned above. It has been reported that carbon components are incorporated into the brain and produce ROS, and that the ROS cause damage to brain cells and Alzheimer's disease and cognitive disorders in the elderly.From these lines of evidence, the author would like to emphasize that the main toxicity of PM2.5 is due to carbon components, and it is important to take countermeasures to decrease the concentration of carbon components in ambient air.


Assuntos
Poluentes Atmosféricos/toxicidade , Carbono/toxicidade , Material Particulado/toxicidade , Sulfatos/toxicidade , Doença de Alzheimer/etiologia , Animais , Asma/etiologia , Doenças Cardiovasculares/etiologia , Epigênese Genética , Cobaias , Humanos , Camundongos , Neoplasias/etiologia , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo
8.
Sci Total Environ ; 687: 839-848, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31412487

RESUMO

The adverse effects of air pollution have been long studied in the lung and respiratory systems, but the molecular changes that this causes at the central nervous system level have yet to be fully investigated and understood. To explore the evolution with time of protein expression levels in the brain of rats exposed to particulate matter of different sizes, we carried out two-dimensional gel electrophoresis followed by determination of dysregulated proteins through Coomassie blue staining-based densities (SameSpots software) and subsequent protein identification using MALDI-based mass spectrometry. Expression differences in dysregulated proteins were found to be statistically significant with p-value <0.05. A systems biology-based approach was utilized to determine critical biochemical pathways involved in the rats' brain response. Our results suggest that rats' brains have a particulate matter size dependent-response, being the mitochondrial activity and the astrocyte function severely affected. Our proteomic study confirms the dysregulation of different biochemical pathways involving energy metabolism, mitochondrial activity, and oxidative pathways as some of the main effects of PM exposure on the rat brain. SIGNIFICANCE: Rat brains exposed to particulate matter with origin in car engines are affected in two main areas: mitochondrial activity, by the dysregulation of many pathways linked to the respiratory chain, and neuronal and astrocytic function, which stimulates brain changes triggering tumorigenesis and neurodegeneration.


Assuntos
Poluentes Atmosféricos/toxicidade , Encéfalo/metabolismo , Material Particulado/toxicidade , Proteoma/metabolismo , Poluição do Ar/estatística & dados numéricos , Animais , Metabolismo Energético/efeitos dos fármacos , Masculino , Estresse Oxidativo/fisiologia , Proteômica , Ratos
9.
Sci Total Environ ; 691: 874-884, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31326811

RESUMO

Exposure to fine particulate matter (PM2.5) increases the risk of metabolic diseases, such as cancer and cardiovascular disease. Disturbed hepatocyte metabolism accelerates the incidence and progression of metabolic diseases. However, toxic effects of PM2.5 on hepatocyte metabolism remain unclear. Accordingly, an untargeted metabolomics approach based on liquid chromatography-mass spectrometry was used to characterize comprehensive metabolic responses of HepG2 cells to PM2.5 exposure and to discover potential therapeutic targets for PM2.5-induced metabolic dysregulation in metabolic diseases. Metabolomics revealed that exposure to liposoluble extracts of PM2.5 samples (LE) triggered substantial changes in 46 metabolic pathways, mainly involved in lipid, amino acid, nucleotide and carbohydrate metabolism, in HepG2 cells. Notably, LE exposure induced accumulation of FFAs and medium-chained acylcarnitines (6-12 carbons), but decreased levels of short-chained acylcarnitines (<5 carbons) in HepG2 cells. Meanwhile, levels of citrate/isocitrate and aconitate were decreased, while 2-hydroxyglutate and succinate accumulated in HepG2 cells treated with LE. Additionally, levels of adenosine triphosphate, guanosine triphosphate, uridine triphosphate and cytidine triphosphate were decreased; however, contents of adenosine monophosphate, guanosine monophosphate, purines and pyrimidines were increased in HepG2 cells treated with LE. Moreover, levels of glutathione, Glu-Cys, Cys-Gly, lipoic acid, methionine sulfoxide, methionine and S-adenosyl-L-methionine were increased, while those of most amino acids were decreased in HepG2 cells treated with LE. These data demonstrated that LE exposure triggered accumulation of FAAs and oncometabolites (2-hydroxyglutate and succinate), mitochondrial dysfunctions characterized by incomplete FFA oxidation and reduced energy supply from TCA cycle and oxidative phosphorylation, disturbances in methylation and redox homeostasis, and the inhibition of most amino acid metabolism in HepG2 cells. Above metabolic disorders indicates potential therapeutic targets for treating PM2.5-induced injury and diseases. To the best of our knowledge, this study provides the first evidence that LE exposure triggered accumulation of medium-chain acylcarnitines, oncometabolites, purines and pyrimidines in HepG2 cells.


Assuntos
Poluentes Atmosféricos/toxicidade , Metaboloma/efeitos dos fármacos , Material Particulado/toxicidade , Cromatografia Líquida , Glutationa , Células Hep G2 , Hepatócitos , Humanos , Lipídeos , Redes e Vias Metabólicas , Metabolômica , Oxirredução , Espectrometria de Massas em Tandem
10.
Chem Biol Interact ; 311: 108762, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31348917

RESUMO

Neurotoxicity caused by particulate matter (PM) has been highlighted as being a potential risk factor for neurodegenerative diseases. However, the effects of brain inflammation in response to traffic-related PM remain unclear. The objective of this study was to investigate the effects of traffic-related PM on microglial responses. We determined the cytotoxicity, oxidative stress, lipid peroxidation, inflammation, activation, autophagy, and apoptosis due to exposure to carbon black (CB) and diesel exhaust particles (DEPs) in Bv2 microglial cells. Additionally, cells were pretreated with corticosteroid to determine alterations in microglial activation and inflammation. For in vivo confirmation, Sprague Dawley (SD) rats were whole-body exposed to traffic-related PM1 (PM with an aerodynamic diameter of <1 µm) for 3 and 6 months. We observed that a decrease in cell viability and increases in dichlorodihydrofluorescein (DCFH), lactate dehydrogenase (LDH), and thiobarbituric acid-reactive substances (TBARSs) occurred due to CB and DEP. Production of interleukin (IL)-6 and soluble tumor necrosis factor (TNF)-α was significantly stimulated by CB and DEP, whereas production of cellular TNF-α was significantly stimulated by CB. Iba1 and prostaglandin E2 (PGE2) significantly increased due to CB and DEP. Consistently, we observed significant increases in Iba1 in the hippocampus of rats after 3 and 6 months of exposure to traffic-related PM1. We found that the light chain 3II (LC3II)/LC3I ratio and caspase-3 activity increased due to CB and DEP exposure. Subsequently, LDH, TBARS, LC3II/I, and caspase-3 activities did not clearly respond to corticosteroid pretreatment followed by DEP exposure in BV2 cells. Results of the present study suggested that traffic-related PM induced cytotoxicity, lipid peroxidation, microglial activation, and inflammation as well as autophagy and caspase-3 regulation in microglia. We demonstrated that microglial activation and inflammation may play important roles in the response of the brain to traffic-related PM.


Assuntos
Inflamação/etiologia , Microglia/efeitos dos fármacos , Material Particulado/toxicidade , Animais , Autofagia/efeitos dos fármacos , Encéfalo/patologia , Proteínas de Ligação ao Cálcio/análise , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dinoprostona/análise , Interleucina-6/metabolismo , L-Lactato Desidrogenase/metabolismo , Masculino , Proteínas dos Microfilamentos/análise , Microglia/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima/efeitos dos fármacos , Emissões de Veículos/toxicidade
11.
Ecotoxicol Environ Saf ; 182: 109425, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31295660

RESUMO

BACKGROUND: Inhalation of fine particulate matter (PM2.5) induces the occurrence of lung inflammation and fibrosis, but its molecular mechanism remains unclear. Resveratrol (RES) is known to have anti-inflammatory properties in many pulmonary diseases. Here, we aimed to investigate the effect of long-term "real-world" ambient PM exposure on lung inflammation and fibrosis and further explore the protective effect and mechanism of RES. METHODS AND RESULTS: RES (50 and 100 mg/kg.bw) was administered to C57BL/6J mice that were exposed to ambient PM for 5 months. The control group breathed filtered air without RES, and the PM group was exposed to PM without RES. The inflammatory cytokine levels in bronchoalveolar lavage fluid (BALF) and lung fibrosis were evaluated by enzyme-linked immune sorbent assay (ELISA) kits and Masson's trichrome staining. The real-time PCR and Western blot analysis were used to determine the signal pathway. In vivo, PM exposure markedly elevated the levels of inflammatory cytokines and TGF-ß1 in BALF, induced lung fibrosis. Meanwhile, PM exposure triggered autophagy process and activated the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome in lung. Also, RES treatment abolished PM-induced lung inflammation and fibrosis, and inhibited autophagic process and NLRP3 inflammasome activation. In vitro, PM2.5-induced cytotoxicity in BEAS-2B cells dose-dependently. Besides, RES alleviated PM2.5-induced cytotoxicity, inhibited autophagic process and NLRP3 inflammasome activity and decreased IL-1ß production in BEAS-2B cells. CONCLUSION: Long-term PM exposure induced lung inflammation and fibrosis, and RES intervention alleviated these adverse effects via inhibiting autophagy-related NLRP3 inflammasome activation.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Fibrose/tratamento farmacológico , Material Particulado/toxicidade , Pneumonia/tratamento farmacológico , Resveratrol/uso terapêutico , Animais , Citocinas/metabolismo , Inibidores Enzimáticos/uso terapêutico , Inflamassomos/metabolismo , Pulmão/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pneumonia/induzido quimicamente , Proteínas , Fibrose Pulmonar , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta1
12.
Sci Total Environ ; 690: 209-216, 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31288112

RESUMO

Failure of large, concrete structures can lead to the generation of very small fragments, including aerosols in the fine fraction, which have aerodynamic diameters of ≤2.5 µm (PM2.5). These aerosols can persist in the environment, pose exposure risks, and potentially cause negative health effects. New trends in construction favor the use of concrete reinforced with steel fibers, but little is known about the nature of the fragments generated during its failure. This study investigated the fragmentation of several steel-fiber reinforced concrete formulations using dynamic compression testing. The release of tumor necrosis factor alpha (TNF-α), an inflammatory marker widely used in both human and animal studies, was then analyzed to determine the effects of the fragments in the aerosol fine fraction on mouse macrophages (RAW 264.7). All concrete formulations studied showed statistically increased TNF-α release, which was inversely correlated with fiber length and fiber content (% weight). In addition, results from a select set of concrete formulations also showed a clear dose-response relationship. This paper postulates the fracture mechanisms by which concrete parameters (i.e., fiber length and content) lead to the generation of PM2.5, producing the observed TNF-α release.


Assuntos
Poluentes Atmosféricos/toxicidade , Materiais de Construção , Macrófagos/efeitos dos fármacos , Material Particulado/toxicidade , Fator de Necrose Tumoral alfa/metabolismo , Animais , Macrófagos/metabolismo , Camundongos
13.
Chemosphere ; 233: 711-723, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31200131

RESUMO

Considering the unique physiochemical properties of concentrated ambient particles (CAPs), it is extremely important to be aware of their toxic effect. A number of studies have investigated the vascular toxicity of CAPs, while potential mechanisms are still not clearly defined. Differentially expressed mRNAs, miRNAs and lncRNAs were analyzed in EA.hy926 endothelial cells after incubation with 2.5 and 10 µg/cm2 urban particulate matter SRM 1648a for 24 h. As a result, the microarray profile showed that 97 mRNA, 18 miRNA, and 356 lncRNA transcripts are dysregulated in 2.5 µg/cm2 group. And the expression of 440 mRNAs, 40 miRNAs, and 1283 lncRNAs significantly changes in 10 µg/cm2 group. Through the miRNA-mRNA-transcription factor (TF) network, hsa-miR-128-3p, miR-18-5p and miR-376a-3p, miR-4306 as well, are key miRNAs in SRM 1648a-induced endothelial damage. Withal, lncRNA-mRNA-TF analysis hinted the importance of lncRNA T018951 and T200627. Subsequently, competing endogenous RNA (CeRNA) network was constructed for the comprehensive analysis of the regulation dogma between mRNAs and non-coding RNAs. It suggested that 35 GO terms and 1 KEGG pathway are significantly enriched in 2.5 µg/cm2 group. Meanwhile, 185 terms and 18 pathways are important in 10 µg/cm2 group. Pathway analysis revealed that Gap junction, Ras and MAPK signaling pathways are most significant in endothelial cell lesion. In conclusion, integrative analysis of mRNA and non-coding RNA in human endothelial cells suggests that a vast majority of non-coding RNAs regulate vascular toxicity in response to SRM 1648a. Moreover, it highlights the need for comprehensive analysis of latent mechanisms through a combination of signaling pathways with epigenetics studies.


Assuntos
Poluentes Ambientais/química , Material Particulado/química , Material Particulado/toxicidade , Linhagem Celular , Células Endoteliais/metabolismo , Poluentes Ambientais/toxicidade , Regulação da Expressão Gênica , Humanos , MicroRNAs/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais , Fatores de Transcrição/metabolismo
14.
Adv Exp Med Biol ; 1176: 101-108, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31175637

RESUMO

Exposure to urban airborne particulate matter (PM) associates with adverse health effects, but the exact mechanisms remain unclear. In this study, we focused on cytotoxicity (MTT), oxidative stress (DCF/FC), DNA damage (PI/FC), necrosis/apoptosis (FC), and autophagy (LC3 expression; WB/FC) triggered by urban dust (UD) in naïve human alveolar epithelial A549 cells and in the cells with reduced glutathione (GSH). The A549 cells were grown in F12K/FCS media supplemented with coarse carbon black (CB; Huber990; 260 nm diameter; 200 µg·ml-1) or urban dust (UD; Standard Reference Materials; 200 µg·ml-1) for 24 h. To deplete intracellular glutathione (GSH), l-buthionine-(S,R)-sulfoximine (BSO; 100 mM; 24 h) was used. Pre-treatment with BSO depleted the cellular GSH by about 30%. A similar effect was noticed after UD. The CB was without any effects on the parameters tested, except for LC3 expression (autophagy) which increased by about twofold. However, UD decreased cell viability by about 27%, decreased cell proliferation in BSO pre-treated cells, increased ROS production, and increased both Hsp70 and LC3 proteins by about twofold, but most changes were unrelated to ROS-mediated GSH depletion. We conclude that urban dust-induced oxidative stress is important in PM toxicity, but other as yet unrecognized mechanisms are also involved.


Assuntos
Células Epiteliais Alveolares , Autofagia , Poeira , Estresse Oxidativo , Material Particulado , Células A549 , Células Epiteliais Alveolares/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Glutationa/metabolismo , Humanos , Estresse Oxidativo/efeitos dos fármacos , Material Particulado/toxicidade , Espécies Reativas de Oxigênio
15.
Environ Sci Pollut Res Int ; 26(23): 23958-23966, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31218585

RESUMO

Health risks have been closely related to increased exposure of fine particulate matter (PM2.5) in general population. Immune system is considered to be a most vulnerable target for airborne pollutants. PM2.5 could make some serious damages to the body organs by inducing immunotoxicity. However, the underlying molecular mechanisms are still unclear. The purpose of this study is aimed to elucidate the possible mechanisms of PM2.5-mediated immunotoxicity on spleen organ by using SD rat models. This research demonstrated that the spleen structure damage induced by PM2.5 treatment was more pronounced in winter than in summer. Mechanistically, TUNEL staining show a considerable increase in spleen apoptosis by summer and winter PM2.5 exposures compared with control. However, winter PM2.5 exposure caused more toxicity in the spleen than summer PM2.5 exposure. Furthermore, our results illustrated that PM2.5 triggered oxidative stress and ERS in spleen tissues of SD rats, and lead to apoptosis via upregulation of CHOP and caspase-12. Likewise, the protein levels of LC3 were significantly increased and p62 was decreased by PM2.5 exposure, thereby activated the autophagy of spleen in SD rats in a concentration-dependent manner. In conclusion, this study supported that PM2.5 mediated the immunotoxicity by the occurrence of stimulation of ERS and autophagy in SD rats. Taken together, these findings suggest PM2.5 as potential agent of immunotoxicity that needs an urgent attention. Graphical abstract Graphical abstract contains poor quality of text inside the artwork. Please do not re-use the file that we have rejected or attempt to increase its resolution and re-save. It is originally poor, therefore, increasing the resolution will not solve the quality problem. We suggest that you provide us the original format. We prefer replacement figures containing vector/editable objects rather than embedded images. Preferred file formats are eps, ai, tiff and pdf.Thanks you attention. We will provide tiff format image.


Assuntos
Poluentes Atmosféricos/toxicidade , Sistema Imunitário/efeitos dos fármacos , Material Particulado/toxicidade , Poluentes Atmosféricos/análise , Animais , Apoptose , Autofagia , Marcação In Situ das Extremidades Cortadas , Masculino , Estresse Oxidativo , Material Particulado/análise , Ratos , Ratos Sprague-Dawley , Estações do Ano , Baço
16.
Environ Sci Pollut Res Int ; 26(24): 25326-25340, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31254199

RESUMO

Exposure to PM10 generated by biomass burning may reduce lung function and induce cytogenetic effects, especially in chronic obstructive pulmonary disease patients. This study investigated the frequency of DNA-damaged cells, cells with cytokinetic defect, and different types of cell death using a buccal micronucleus cytome assay. The correlations between each biomarker and lung function were investigated. The changes in these biomarkers associated with high pollutant levels (PM10 > 50 µg/m3) and low pollutant levels (PM10 < 50 µg/m3) were evaluated to explore whether PM10 exposure induced genotoxic damages and cytokinetic defects in COPD patients when the daily average PM10 concentration reached above 50 µg/m3. Fifty-eight COPD patients and 26 healthy subjects living in Chiang Dao district, Chiang Mai, Thailand, were recruited in this study. The results revealed that buccal cells with micronuclei (high vs low 1.09 ± 1.95 vs 0.29 ± 0.64 in COPD patients) and binucleated cells (high vs low 11.43 ± 18.68 vs 1.60 ± 1.31 and 7.77 ± 12.76 vs 1.00 ± 1.17 in COPD and healthy subjects, respectively) observed during the high pollutant period were more frequent than in the low pollutant period. Moreover, exposure to PM10 increased the risk of micronucleus induction in COPD patients 295.23-fold.


Assuntos
Dano ao DNA , Material Particulado/toxicidade , Doença Pulmonar Obstrutiva Crônica/patologia , Idoso , Biomarcadores , Biomassa , Morte Celular , Citocinese , Feminino , Humanos , Masculino , Testes para Micronúcleos , Pessoa de Meia-Idade , Mucosa Bucal , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Tailândia/epidemiologia
17.
Environ Pollut ; 252(Pt B): 1235-1245, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31252121

RESUMO

Previous meta-analyses on associations between air pollution (AP) and type 2 diabetes mellitus (T2DM) were mainly focused on studies conducted in high-income countries. Evidence should be updated by including more recent studies, especially those conducted in low- and middle-income countries. We therefore conducted a systematic review and meta-analysis of epidemiological studies to conclude an updated pooled effect estimates between long-term AP exposure and the prevalence and incidence of T2DM. We searched PubMed, Embase, and Web of Science to identify studies regarding associations of AP with T2DM prevalence and incidence prior to January 2019. A random-effects model was employed to analyze the overall effects. A total of 30 articles were finally included in this meta-analysis. The pooled results showed that higher levels of AP exposure were significantly associated with higher prevalence of T2DM (per 10 µg/m3 increase in concentrations of particles with aerodynamic diameter < 2.5 µm (PM2.5): odds ratio (OR) = 1.09, 95% confidence interval (95%CI): 1.05, 1.13; particles with aerodynamic diameter < 10 µm (PM10): OR = 1.12, 95%CI: 1.06, 1.19; nitrogen dioxide (NO2): OR = 1.05, 95%CI:1.03, 1.08). Besides, higher level of PM2.5 exposure was associated with higher T2DM incidence (per 10 µg/m3 increase in concentration of PM2.5: hazard ratio (HR) = 1.10, 95%CI:1.04, 1.16), while the associations between PM10, NO2 and T2DM incidence were not statistically significant. The associations between AP exposure and T2DM prevalence showed no significant difference between high-income countries and low- and middle-incomes countries. However, different associations were identified between PM2.5 exposure and T2DM prevalence in different geographic areas. No significant differences were found in associations of AP and T2DM prevalence/incidence between females and males, except for the effect of NO2 on T2DM incidence. Overall, AP exposure was positively associated with T2DM. There still remains a need for evidence from low- and middle-income countries on the relationships between AP and T2DM.


Assuntos
Poluentes Atmosféricos/análise , Poluição do Ar/análise , Diabetes Mellitus Tipo 2/epidemiologia , Exposição Ambiental/análise , Material Particulado/análise , Poluentes Atmosféricos/toxicidade , Diabetes Mellitus Tipo 2/induzido quimicamente , Feminino , Humanos , Incidência , Masculino , Dióxido de Nitrogênio/análise , Razão de Chances , Material Particulado/toxicidade , Prevalência
18.
Sci Total Environ ; 684: 657-669, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31158627

RESUMO

Environmental pollution caused by plastic waste is a growing global problem. Discarded plastic products and debris (microplastic particles) in the oceans detrimentally affect marine ecosystems and may impact human. Humans are exposed to plastic debris via the consumption of seafood and drinking water, contact with food packaging, or inhalation of particles. The accumulation of microplastic particles in humans has potential health risks such as cytotoxicity, hypersensitivity, unwanted immune response, and acute response like hemolysis. We investigated the cellular responses of secondary polypropylene microplastics (PP particles) of approximately ~20 µm and 25-200 µm in different condition and size to normal cells, immune cells, blood cells, and murine immune cells by cytokine analysis, ROS assay, polarization assay and proliferation assay. We found that PP particles showed low cytotoxicity effect in size and concentration manner, however, a high concentration, small sized, DMSO method of PP particles stimulated the immune system and enhanced potential hypersensitivity to PP particles via an increase in the levels of cytokines and histamines in PBMCs, Raw 264.7 and HMC-1 cells.


Assuntos
Leucócitos/efeitos dos fármacos , Material Particulado/toxicidade , Polipropilenos/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Linhagem Celular , Humanos , Camundongos , Tamanho da Partícula , Células RAW 264.7
19.
Environ Sci Pollut Res Int ; 26(20): 20581-20594, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31104233

RESUMO

The reduction of estrogen levels, as a result of menopause, is associated with the development of metabolic diseases caused by alterations in oxidative stress (OS), inflammatory biomarkers, and 70-kDa heat-shock protein (HSP70) expression. Additionally, exposure to fine particulate matter air pollution modifies liver OS levels and predisposes organisms to metabolic diseases, such as type 2 diabetes (T2DM). We investigated whether ovariectomy affects hepatic tissue and alters glucose metabolism in female rats exposed to particulate air pollution. First, 24 female Wistar rats received an intranasal instillation of saline or particles suspended in saline 5 times per week for 12 weeks. The animals then received either bilateral ovariectomy (OVX) or false surgery (sham) and continued to receive saline or particles for 12 additional weeks, comprising four groups: CTRL, Polluted, OVX, and Polluted+OVX. Ovariectomy increased body weight and adiposity and promoted edema in hepatic tissue, hypercholesterolemia, glucose intolerance, and a pro-inflammatory profile (reduced IL-10 levels and increased IL-6/IL-10 ratio levels), independent of particle exposure. The Polluted+OVX group showed an increase in neutrophils and neutrophil/lymphocyte ratios, decreased antioxidant defense (SOD activity), and increased liver iHSP70 levels. In conclusion, alterations in the reproductive system predispose female organisms to particulate matter air pollution effects by affecting metabolic, oxidative, pro-inflammatory, and heat-shock protein expression.


Assuntos
Proteínas de Choque Térmico HSP70/metabolismo , Inflamação/metabolismo , Ovariectomia/efeitos adversos , Estresse Oxidativo , Material Particulado/toxicidade , Adiposidade/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Glicemia/metabolismo , Citocinas/metabolismo , Feminino , Fígado/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Ganho de Peso/efeitos dos fármacos
20.
Environ Sci Pollut Res Int ; 26(18): 18200-18207, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31041709

RESUMO

Previous studies have shown that exposure to particulate matter (PM) increased variety of health problems, particularly cardiovascular diseases leading to premature mortality. The cardiac effects of particulate matter containing PM10 include increased infarct size, decreased heart function, and increased arrhythmias in experimental ischemia-reperfusion models in rats. The aim of this study was to evaluate the effects of particles with an aerodynamic diameter smaller than 10 µm (PM10) on isolated-rat heart and also to determine the efficacy of gallic acid (GA) as a preventive agent in oxidative damage. The healthy rats were divided into 8 equal groups which served as, control, GA, PM10 (0.5, 2.5, and 5 mg/kg), and PM10+GA groups. PM10 administered into the lungs via the trachea in two stages with 48-h interval. After all experiments, the electrocardiogram was recorded. Then, the hemodynamic parameters and ventricular arrhythmias in rat isolated-hearts were assessed using Langendorff apparatus and according to the Lambeth conventions. In addition, the inflammation and oxidative stress factors in cardiac tissues were evaluated in all groups. The obtained results showed that the exposure to PM caused to decrease in cardiac hemodynamic and electrocardiogram parameters. Also, in PM10 rat groups, the IL-6, TNF-α, and oxidative stress parameters were increased. Gallic acid preserved the value of cardiac parameters and inflammation in rat hearts. In summary, we added a novel therapeutic effect of gallic acid for cardiac dysfunction induced by particulate matter. These findings could be related to antioxidant and antiinflammation properties and the obtained results suggest that natural antioxidant like gallic acid could be a therapeutic agent in prevention and management of health issues in the polluted areas of the world.


Assuntos
Poluentes Atmosféricos/toxicidade , Ácido Gálico/farmacologia , Coração/efeitos dos fármacos , Material Particulado/toxicidade , Substâncias Protetoras/farmacologia , Animais , Arritmias Cardíacas/induzido quimicamente , Eletrocardiografia , Inflamação/induzido quimicamente , Inflamação/complicações , Masculino , Estresse Oxidativo/efeitos dos fármacos , Material Particulado/antagonistas & inibidores , Ratos , Ratos Sprague-Dawley
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