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1.
Artigo em Inglês | MEDLINE | ID: mdl-33525689

RESUMO

Recent technical developments brought negative side effects such as air pollution and large-scale fires, increasingly exposing people to diesel engine exhaust particles (DEP). Testing how DEP inhalation triggers pathophysiology in animal models could be useful in determining how it affects humans. To this end, the aim of this study was to investigate the effects of pulmonary exposure to DEP for seven consecutive days in experimental male C5BL6/N mice. Twenty-four C5BL6/N mice were treated with one of the three test materials: distilled water for control, a low DEP exposure (5 mg/kg), or a high DEP exposure (15 mg/kg). Exposure to DEP induced decreased body weight; however, it gradually increased pulmonary weight in a DEP-dose-dependent manner. DEP exposure significantly elevated soot accumulation in the lungs, with the alteration of pulmonary homeostasis. It also elevated infiltrated immune cells, thus significantly increasing inflammatory cytokine mRNA and protein production in the lungs and broncho-alveolar lavage fluid, respectively. Pulmonary DEP exposure also altered behavioral responses in the open field test (OFT). Low exposure elevated moving distance and speed, while significantly decreasing the number of trials to enter the central zone. Different concentrations of DEP resulted in different behavioral changes; however, while anxiety levels increased, their degree was independent of DEP concentrations. Results suggest that DEP exposure may possess pro-inflammatory responses in the lungs and trigger anxiety.


Assuntos
Pneumonia , Emissões de Veículos , Animais , Ansiedade/induzido quimicamente , Líquido da Lavagem Broncoalveolar , Citocinas , Masculino , Camundongos , Material Particulado/toxicidade , Pneumonia/induzido quimicamente , Emissões de Veículos/toxicidade
2.
Ecotoxicol Environ Saf ; 213: 112035, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33581487

RESUMO

Air pollution has been documented to contribute to severe respiratory diseases like asthma and chronic obstructive pulmonary disorder (COPD). Although these diseases demonstrate a shift in the lung microbiota towards Proteobacteria, the effects of traffic generated emissions on lung microbiota profiles have not been well-characterized. Thus, we investigated the hypothesis that exposure to traffic-generated emissions can alter lung microbiota and immune defenses. Since a large population of the Western world consumes a diet rich in fats, we sought to investigate the synergistic effects of mixed vehicle emissions and high-fat diet consumption. We exposed 3-month-old male C57Bl/6 mice placed either on regular chow (LF) or a high-fat (HF: 45% kcal fat) diet to mixed emissions (ME: 30 µg PM/m3 gasoline engine emissions+70 µg PM/m3 diesel engine emissions) or filtered air (FA) for 6 h/d, 7 d/wk for 30 days. Levels of pulmonary immunoglobulins IgA, IgG, and IgM were analyzed by ELISA, and lung microbial profiling was done using qPCR and Illumina 16 S sequencing. We observed a significant decrease in lung IgA in the ME-exposed animals, compared to the FA-exposed animals, both fed a HF diet. Our results also revealed a significant decrease in lung IgG in the ME-exposed animals both on the LF diet and HF diet, in comparison to the FA-exposed animals. We also observed an expansion of Enterobacteriaceae belonging to the Proteobacteria phylum in the ME-exposed groups on the HF diet. Collectively, we show that the combined effects of ME and HF diet result in decreased immune surveillance and lung bacterial dysbiosis, which is of significance in lung diseases.


Assuntos
Pulmão/microbiologia , Proteobactérias , Emissões de Veículos/toxicidade , Poluição do Ar , Animais , Dieta Hiperlipídica , Disbiose , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microbiota
3.
Ecotoxicol Environ Saf ; 210: 111871, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33422840

RESUMO

AIM: Ambient fine particulate matter (PM2.5) consists of various components, and their respective contributions to the toxicity of PM2.5 remains to be determined. To provide specific recommendations for preventing adverse effects due to PM2.5 pollution, we determined whether the induction of pulmonary inflammation, the putative pathogenesis for the morbidity and mortality due to PM2.5 exposure, was fractioned through solubility-dependent fractioning. METHODS: In the present study, the water and heptane solubilities-dependent serial fractioning of diesel exhaust particulate matter (DEP), a prominent source of urban PM2.5 pollution, was performed. The pro-inflammatory actions of these resultant fractions were then determined using both an intratracheal instillation mouse model and cultured BEAS-2B cells, a human bronchial epithelial cell line. RESULTS: Instillation of the water-insoluble, but not -soluble fraction elicited significant pulmonary inflammatory and acute phase responses, comparable to those induced by instillation of DEP. The water-insoluble fraction was further fractioned using heptane, a polar organic solvent, and instillation of heptane-insoluble, but not -soluble fraction elicited significant pulmonary inflammation and acute phase responses. Furthermore, we showed that DEP and water-insoluble DEP, but not water-soluble DEP, activated pro-inflammatory signaling in cultured BEAS-2B cells, ruling out the possibility that the solubility impacts the in vivo distribution and thus the pulmonary inflammatory response.


Assuntos
Reação de Fase Aguda/induzido quimicamente , Poluentes Atmosféricos/toxicidade , Inflamação/induzido quimicamente , Pulmão/efeitos dos fármacos , Material Particulado/toxicidade , Emissões de Veículos/toxicidade , Reação de Fase Aguda/patologia , Animais , Brônquios/citologia , Linhagem Celular , Células Epiteliais/efeitos dos fármacos , Humanos , Inflamação/patologia , Pulmão/patologia , Masculino , Camundongos Endogâmicos C57BL
4.
Environ Toxicol Pharmacol ; 83: 103583, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33434645

RESUMO

Air pollution has association with chronic obstructive pulmonary disease (COPD) and reduced life expectancy. This study investigated the deleterious effects caused by tobacco smoke and diesel exhaust particles (DEP) from vehicles operating under EURO 3 and EURO 5 standards. Experiments were carried out on C57BL/6 mice divided into six groups: control group, group exposed to cigarette smoke (CS), two groups exposed to DEP (AAE3 and AAE5), and two groups exposed to tobacco smoke and vehicle DEP (CSE3 and CSE5). Results showed that, when compared to AA, groups AAE3 and AAE5 showed changes in respiratory mechanics, and that DEP originating from EURO 5 diesel vehicles was less harmful when compared to DEP originating from EURO 3 diesel vehicles. Analyses of groups CSE3 and CSE5 revealed increased inspiratory capacity and decreased tissue elastance, when compared to their respective controls, suggesting an exacerbation of changes in respiratory system mechanics compatible with COPD development.


Assuntos
Poluentes Atmosféricos/toxicidade , Pulmão/efeitos dos fármacos , Fumaça/efeitos adversos , Emissões de Veículos/toxicidade , Animais , Enfisema/patologia , Enfisema/fisiopatologia , Pulmão/patologia , Pulmão/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Veículos Automotores , Tabaco , Produtos do Tabaco
5.
Environ Toxicol Pharmacol ; 83: 103584, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33460804

RESUMO

Airway pollution can affect the central nervous system, but whether this causes glial activation and inflammation in the nucleus of solitary tract (NTS) remains unclear. We used a rat model with exposure to diesel exhaust particulate matter (DEP) at 200 µg/m3 (low exposure) and 1000 µg/m3 (high exposure) for 14 days. Activation of microglia and astrocytes in the NTS was assessed using Iba-1 and glial fibrillary acidic protein (GFAP) staining. The expression of neurotrophic factors including brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), and nerve growth factor (NGF) in the NTS were evaluated by immunofluorescence. Changes in the intracellular structure of NTS neurons were observed via electron microscopy. Inflammatory cytokines and oxidant stress levels in the medulla were also measured. Exposure to DEP can cause NTS inflammation as well as airway inflammation, especially in the H-exposure group. We showed that the numbers of microglia and astrocytes in the NTS, as well as NGF expression in the NTS, were significantly higher in both exposure groups than in controls, but BDNF or GDNF expression was not detected. Exposure to DEP induced ultrastructural changes in NTS neurons as reflected by endoplasmic reticulum dilation, ribosomal loss, mitochondrial vacuolization, and a sparse myelin sheath. Medulla inflammation and an imbalance of oxidants and antioxidants also resulted from exposure to DEP. The H-exposure group showed an imbalance of oxidants and antioxidants with decreased levels of SOD and GSH and increased levels of MDA and ROS compared to the control group (both p < 0.01) in the medulla. Inflammatory cytokines (IL-1ß, IL-6, and TNF-α) were also significantly increased in the H-exposure group. Fourteen days of exposure to DEP can affect the NTS neurons in rat. Glial activation and inflammation may play important roles in the response of the NTS to DEP.


Assuntos
Poluentes Atmosféricos/toxicidade , Encéfalo/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Neuroglia/efeitos dos fármacos , Emissões de Veículos/toxicidade , Administração por Inalação , Animais , Encéfalo/patologia , Encéfalo/ultraestrutura , Inflamação/etiologia , Inflamação/patologia , Pulmão/patologia , Masculino , Microscopia Eletrônica , Neuroglia/patologia , Neuroglia/ultraestrutura , Ratos Sprague-Dawley
6.
Int J Mol Sci ; 22(2)2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33430368

RESUMO

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired social communication, poor social interactions, and repetitive behaviors. We aimed to examine autism-like behaviors and related gene expressions in rats exposed to diesel exhaust (DE)-origin secondary organic aerosol (DE-SOA) perinatally. Sprague-Dawley pregnant rats were exposed to clean air (control), DE, and DE-SOA in the exposure chamber from gestational day 14 to postnatal day 21. Behavioral phenotypes of ASD were investigated in 10~13-week-old offspring using a three-chambered social behavior test, social dominance tube test, and marble burying test. Prefrontal cortex was collected to examine molecular analyses including neurological and immunological markers and glutamate concentration, using RT-PCR and ELISA methods. DE-SOA-exposed male and female rats showed poor sociability and social novelty preference, socially dominant behavior, and increased repetitive behavior. Serotonin receptor (5-HT(5B)) and brain-derived neurotrophic factor (BDNF) mRNAs were downregulated whereas interleukin 1 ß (IL-ß) and heme oxygenase 1 (HO-1) mRNAs were upregulated in the prefrontal cortex of male and female rats exposed to DE-SOA. Glutamate concentration was also increased significantly in DE-SOA-exposed male and female rats. Our results indicate that perinatal exposure to DE-SOA may induce autism-like behavior by modulating molecules such as neurological and immunological markers in rats.


Assuntos
Poluentes Atmosféricos/toxicidade , Transtorno do Espectro Autista/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Emissões de Veículos/toxicidade , Aerossóis/toxicidade , Animais , Transtorno do Espectro Autista/induzido quimicamente , Fator Neurotrófico Derivado do Encéfalo/genética , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/genética , Humanos , Interleucina-1beta/genética , Masculino , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , Ratos , Ratos Sprague-Dawley , Receptores de Serotonina/genética
7.
Sci Total Environ ; 751: 142235, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-33181987

RESUMO

Inhaled particulate matter (PM) from combustion- and friction-sourced air pollution adversely affects organs distant from the lung. A putative mechanism for the remote effect of inhaled PM is that ultrafine, nano-sized fraction (<100 nm) translocates across the air-tissue barrier, directly interacting with phagocytic tissue cells. Although PM is reported in other tissues, whether it is phagocytosed by non-respiratory tissue resident cells is unclear. Using the placenta as an accessible organ for phagocytic cells, we sought to seek evidence for air pollution-derived PM in tissue resident phagocytes. Macrophage-enriched placental cells (MEPCs) were isolated, and examined by light and electron microscopy. MEPC carbon was assessed by image analysis (mean µm2/1000 cells); particle composition and numbers were investigated using magnetic analyses and energy dispersive X-ray spectroscopy. MEPCs phagocytic capacity was assessed by culture with diesel exhaust PM in vitro. Fifteen placentas were analysed. Black inclusions morphologically compatible with inhaled PM were identified within MEPCs from all samples (mean ± SEM carbon loading, 1000 MEPCs/participant of 0.004 ± 0.001 µm2). High resolution scanning/transmission electron microscopy revealed abundant nano-sized particle aggregates within MEPCs. MEPC PM was predominantly carbonaceous but also co-associated with a range of trace metals, indicative of high temperature (i.e. exogenous) generation. MEPCs contained readily-measurable amounts of iron-rich, ferrimagnetic particles, in concentrations/particle number concentrations ranging, respectively, from 8 to 50 ng/g and 10 to 60.107 magnetic particles/g (wet wt) MEPCs. Extracted MEPCs (n = 20/ placenta) were phagocytic for PM since all cells showed increased carbon area after culture with diesel PM in vitro (mean ± SEM increase 7.55 ± 1.26 µm2 carbon PM). These findings demonstrate that inhaled, metal-bearing, air pollution-derived PM can not only translocate to distant organs, but is taken up by tissue resident phagocytes in vivo. The human placenta, and hence probably the fetus, thus appears to be a target for such particles.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Nanopartículas , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/análise , Feminino , Humanos , Tamanho da Partícula , Material Particulado/análise , Gravidez , Emissões de Veículos/análise , Emissões de Veículos/toxicidade
8.
Ecotoxicol Environ Saf ; 209: 111753, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33348255

RESUMO

Emerging evidence demonstrated that traffic-related air pollution induced adverse effects on cardiovascular system. We designed a population-based cross-sectional study to explore the association between residential proximity to major roadways, traffic density and the prevalence of valvular heart disease (VHD). A total of 34040 subjects from a Rural Health Project between 2013 and 2018 were collected. According to the inclusion and exclusion criteria, 4158 participants were enrolled in the final analysis. And we calculated the subjects' proximity to major roadways and collected the traffic density on the major roadways. Transthoracic echocardiography (TTE) was performed to diagnose the VHD, according to the current AHA/ACC (the American Heart Association and the American College of Cardiology) guidelines. Differences between groups were examined by the one-way ANOVAs for continuous variables and the chi-square tests for categorical variables. A logistic regression models were used to assess the associations. The stratified analysis by age and sex were conducted to further analyze the association. The restricted cubic spline analysis was performed to further evaluate the association between road way distance and VHD. Bonferroni test was used to adjust the significance level. The subjects closer to the major roads had the higher risk of tricuspid regurgitation (TR) (odds risk, OR = 1.519, 95% confidence intervals, 95%CI: 1.058-2.181), especially in female. The risk of VHD was positive (high traffic density VS low traffic density, OR = 1.799, 95%CI: 1.221-2.651), especially in female. In addition, the high traffic density was associated with the risk of mitral regurgitation (MR) (OR = 1.758, 95%CI: 1.085-2.848). The restricted cubic spline analysis found a threshold distance of about 300 m, where had the lowest risk of VHD, aortic regurgitation (AR), MR, TR. Our results found a positive association between traffic-related air pollution and VHD especially in female.


Assuntos
Poluição do Ar/estatística & dados numéricos , Exposição Ambiental/estatística & dados numéricos , Doenças das Valvas Cardíacas/epidemiologia , Emissões de Veículos/toxicidade , Adulto , Estudos Transversais , Ecocardiografia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência
9.
Toxicol Lett ; 339: 39-50, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33373663

RESUMO

Traffic-generated air pollutants have been correlated with alterations in blood-brain barrier (BBB) integrity, which is associated with pathologies in the central nervous system (CNS). Much of the existing literature investigating the effects of air pollution in the CNS has predominately been reported in males, with little known regarding the effects in females. As such, this study characterized the effects of inhalation exposure to mixed vehicle emissions (MVE), as well as the presence of female sex hormones, in the CNS of female ApoE-/- mice, which included cohorts of both ovariectomized (ov-) and ovary-intact (ov+) mice. Ov + and ov- were placed on a high-fat diet and randomly grouped to be exposed to either filtered-air (FA) or MVE (200 PM/m3: 50 µg PM/m3 gasoline engine + 150 µg PM/m3 from diesel engine emissions) for 6 h/d, 7d/wk, for 30d. MVE-exposure resulted in altered cerebral microvascular integrity and permeability, as determined by the decreased immunofluorescent expression of tight junction (TJ) proteins, occludin, and claudin-5, and increased IgG extravasation into the cerebral parenchyma, compared to FA controls, regardless of ovary status. Associated with the altered cerebral microvascular integrity, we also observed an increase in matrix metalloproteinases (MMPs) -2/9 activity in the MVE ov+, MVE ov-, and FA ov- groups, compared to FA ov+. There was also elevated expression of intracellular adhesion molecule (ICAM)-1, inflammatory interleukins (IL-1, IL-1ß), and tumor necrosis factor (TNF-α) mRNA in the cerebrum of MVE ov + and MVE ov- animals. IκB kinase (IKK) subunits IKKα and IKKß mRNA expressions were upregulated in the cerebrum of MVE ov- and FA ov- mice. Our findings indicate that MVE exposure mediates altered integrity of the cerebral microvasculature correlated with increased MMP-2/9 activity and inflammatory signaling, regardless of female hormones present.


Assuntos
Poluentes Atmosféricos/toxicidade , Encéfalo/efeitos dos fármacos , Sistema Nervoso Central/efeitos dos fármacos , Inflamação/induzido quimicamente , Camundongos/genética , Microvasos/efeitos dos fármacos , Emissões de Veículos/toxicidade , Animais , Apolipoproteínas E/efeitos dos fármacos , Feminino , Humanos , Modelos Animais , Fragmentos de Peptídeos/efeitos dos fármacos
10.
J Environ Sci (China) ; 101: 326-338, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33334527

RESUMO

This work assessed the impact of fuelling an automotive engine with palm biodiesel (pure, and two blends of 10% and 20% with diesel, B100, B10 and B20, respectively) operating under representative urban driving conditions on 17 priority polycyclic aromatic hydrocarbon (PAH) compounds, oxidative potential of ascorbic acid (OPAA), and ecotoxicity through Daphnia pulex mortality test. PM diluted with filtered fresh air (WD) gathered in a minitunel, and particulate matter (PM) collected directly from the exhaust gas stream (W/oD) were used for comparison. Results showed that PM collecting method significantly impact PAH concentration. Although all PAH appeared in both, WD and W/oD, higher concentrations were obtained in the last case. Increasing biodiesel concentration in the fuel blend decreased all PAH compounds, and those with 3 and 5 aromatic rings were the most abundant. Palm biodiesel affected both OPAA and ecotoxicity. While B10 and B20 exhibited the same rate of ascorbic acid (AA) depletion, B100 showed significant faster oxidation rate during the first four minutes and oxidized 10% more AA at the end of the test. B100 and B20 were significantly more ecotoxic than B10. The lethal concentration LC50 for B10 was 6.13 mg/L. It was concluded that palm biodiesel decreased PAH compounds, but increased the oxidative potential and ecotoxicity.


Assuntos
Poluentes Atmosféricos , Hidrocarbonetos Policíclicos Aromáticos , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Biocombustíveis/análise , Biocombustíveis/toxicidade , Gasolina/análise , Gasolina/toxicidade , Estresse Oxidativo , Óleo de Palmeira , Material Particulado/análise , Material Particulado/toxicidade , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Emissões de Veículos/análise , Emissões de Veículos/toxicidade
11.
Sci Total Environ ; 750: 141700, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32861077

RESUMO

Despite adverse health effects, ultrafine particulate matter (UFP), i.e., PM less than 0.1 µm in diameter, is an emerging pollutant not subject to regulation. UFP may cause both lung inflammation and cardiopulmonary disease and may enter the brain directly via the olfactory bulb, affecting the nervous system. In highly urbanized environments, diesel and gasoline vehicles are among the major sources of UFP including combustion-generated solid particle pollutant and metal-based particles. Metal-based UFP are of much concern, as they may promote inflammation and DNA damage via oxidative stress with generation of free radicals and reactive oxygen species (ROS). We used the honeybee as an alternative sampling system of UFP in an area of the Po Valley (Northern Italy), which is subject to intense traffic. Worker bees are widely recognised as efficient samplers of air pollutants, including airborne PM. During flight and foraging activity, pubescence of the bees promotes the accumulation of electrical charge on the body's surface, enhancing attraction to air pollutants. Bees living near the main Italian highway, the Autostrada A1, displayed a contamination of nanosized Fe-oxides/hydroxides and baryte. Sources of Fe-bearing and baryte ultrafine particles are primarily the vehicles speeding on the motorway. Pollen collected by forager bees and honey produced by the bee colony displayed contamination by nanosized Fe-oxides/hydroxides and baryte. Such a contamination exposes pollinators and humans to UFP ingestion, endangering the safety of food produced at traffic-influenced sites. Given the global spread of traffic, our findings suggest that exposure and environmental impact of ultrafine Fe-oxides/hydroxides and baryte are potentially ubiquitous, although usually overlooked in environmental policy discussions.


Assuntos
Poluentes Atmosféricos , Emissões de Veículos , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Animais , Abelhas , Poeira , Humanos , Itália , Tamanho da Partícula , Material Particulado/análise , Material Particulado/toxicidade , Emissões de Veículos/análise , Emissões de Veículos/toxicidade
12.
Chemosphere ; 268: 129314, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33352509

RESUMO

Our understanding of the impact of in utero exposure to PM on post-natal immune function and the subsequent response to PM exposure is limited. Similarly, very few studies have considered the effect of exposure to PM from different sources. Thus, the aim of this study was to examine how in utero exposure to PM from different sources effects the post-natal response to pro-inflammatory and immune stimuli. C56BL/6J pregnant mice were exposed intranasally on gestational day (E)7.5, E12.5 and E17.5-50 µg of diesel exhaust particles (DEP), silica or saline. At 4-weeks post-natal age, sub-groups of male and female mice were exposed intranasally to 50 µg of DEP or saline. Lung inflammatory responses were assessed 6 h later by quantifying inflammatory cells and cytokine production (MCP-1, MIP-2, IL-6). In separate groups of mice, the spleen was harvested to quantify B and T cell populations. Splenocytes were isolated and exposed to lipopolysaccharide or poly I:C for assessment of cytokine production. Exposure to DEP in utero decreased %CD1dhighCD5+ B cells in female mice and IFN-γ production by splenocytes in both sexes. Male mice had elevations in macrophage and lymphocyte numbers in response to DEP whereas female mice only had elevated IL-6, MCP-1 and MIP-2 levels. In utero exposure to silica had no effect on these measures. These data suggest that in utero exposure to PM alters immune development and post-natal immune function. This response is dependent on the source of PM, which has implications for understanding the community health effects of exposure to air pollution.


Assuntos
Poluição do Ar , Emissões de Veículos , Animais , Feminino , Lipopolissacarídeos , Pulmão , Masculino , Camundongos , Material Particulado/toxicidade , Gravidez , Dióxido de Silício/toxicidade , Emissões de Veículos/toxicidade
13.
Int J Mol Sci ; 22(1)2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33374749

RESUMO

Gasoline engine emissions have been classified as possibly carcinogenic to humans and represent a significant health risk. In this study, we used MucilAir™, a three-dimensional (3D) model of the human airway, and BEAS-2B, cells originating from the human bronchial epithelium, grown at the air-liquid interface to assess the toxicity of ordinary gasoline exhaust produced by a direct injection spark ignition engine. The transepithelial electrical resistance (TEER), production of mucin, and lactate dehydrogenase (LDH) and adenylate kinase (AK) activities were analyzed after one day and five days of exposure. The induction of double-stranded DNA breaks was measured by the detection of histone H2AX phosphorylation. Next-generation sequencing was used to analyze the modulation of expression of the relevant 370 genes. The exposure to gasoline emissions affected the integrity, as well as LDH and AK leakage in the 3D model, particularly after longer exposure periods. Mucin production was mostly decreased with the exception of longer BEAS-2B treatment, for which a significant increase was detected. DNA damage was detected after five days of exposure in the 3D model, but not in BEAS-2B cells. The expression of CYP1A1 and GSTA3 was modulated in MucilAir™ tissues after 5 days of treatment. In BEAS-2B cells, the expression of 39 mRNAs was affected after short exposure, most of them were upregulated. The five days of exposure modulated the expression of 11 genes in this cell line. In conclusion, the ordinary gasoline emissions induced a toxic response in MucilAir™. In BEAS-2B cells, the biological response was less pronounced, mostly limited to gene expression changes.


Assuntos
Brônquios/citologia , Células Epiteliais/efeitos dos fármacos , Emissões de Veículos/toxicidade , Adenilato Quinase/metabolismo , Células Cultivadas , Quebras de DNA de Cadeia Dupla , Impedância Elétrica , Células Epiteliais/metabolismo , Humanos , L-Lactato Desidrogenase/metabolismo , Mucinas/metabolismo , Testes de Toxicidade/métodos , Transcriptoma
14.
Int J Mol Sci ; 21(24)2020 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-33352854

RESUMO

Air pollution is mainly caused by burning of fossil fuels, such as diesel, and is associated with increased morbidity and mortality due to adverse health effects induced by inflammation and oxidative stress. Dimethyl fumarate (DMF) is a fumaric acid ester and acts as an antioxidant and anti-inflammatory agent. We investigated the potential therapeutic effects of DMF on pulmonary damage caused by chronic exposure to diesel exhaust particles (DEPs). Mice were challenged with DEPs (30 µg per mice) by intranasal instillation for 60 consecutive days. After the first 30 days, the animals were treated daily with 30 mg/kg of DMF by gavage for the remainder of the experimental period. We demonstrated a reduction in total inflammatory cell number in the bronchoalveolar lavage (BAL) of mice subjected to DEP + DMF as compared to those exposed to DEPs alone. Importantly, DMF treatment was able to reduce lung injury caused by DEP exposure. Intracellular total reactive oxygen species (ROS), peroxynitrite (OONO), and nitric oxide (NO) levels were significantly lower in the DEP + DMF than in the DEP group. In addition, DMF treatment reduced the protein expression of kelch-like ECH-associated protein 1 (Keap-1) in lung lysates from DEP-exposed mice, whereas total nuclear factor κB (NF-κB) p65 expression was decreased below baseline in the DEP + DMF group compared to both the control and DEP groups. Lastly, DMF markedly reduced DEP-induced expression of nitrotyrosine, glutathione peroxidase-1/2 (Gpx-1/2), and catalase in mouse lungs. In summary, DMF treatment effectively reduced lung injury, inflammation, and oxidative and nitrosative stress induced by chronic DEP exposure. Consequently, it may lead to new therapies to diminish lung injury caused by air pollutants.


Assuntos
Fumarato de Dimetilo/farmacologia , Estresse Oxidativo , Pneumonia/etiologia , Pneumonia/metabolismo , Emissões de Veículos , Poluentes Atmosféricos/efeitos adversos , Animais , Biomarcadores , Líquido da Lavagem Broncoalveolar/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Camundongos , NF-kappa B/metabolismo , Oxirredução , Pneumonia/tratamento farmacológico , Pneumonia/patologia , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Emissões de Veículos/toxicidade
15.
Artigo em Inglês | MEDLINE | ID: mdl-33202948

RESUMO

Growing evidence links prenatal exposure to particulate matter (PM2.5) with reduced lung function and incidence of pulmonary diseases in infancy and childhood. However, the underlying biological mechanisms of how prenatal PM2.5 exposure affects the lungs are incompletely understood, which explains the lack of an ideal in vitro lung development model. Human pluripotent stem cells (hPSCs) have been successfully employed for in vitro developmental toxicity evaluations due to their unique ability to differentiate into any type of cell in the body. In this study, we investigated the developmental toxicity of diesel fine PM (dPM2.5) exposure during hPSC-derived alveolar epithelial cell (AEC) differentiation and three-dimensional (3D) multicellular alveolar organoid (AO) development. We found that dPM2.5 (50 and 100 µg/mL) treatment disturbed the AEC differentiation, accompanied by upregulation of nicotinamide adenine dinucleotide phosphate oxidases and inflammation. Exposure to dPM2.5 also promoted epithelial-to-mesenchymal transition during AEC and AO development via activation of extracellular signal-regulated kinase signaling, while dPM2.5 had no effect on surfactant protein C expression in hPSC-derived AECs. Notably, we provided evidence, for the first time, that angiotensin-converting enzyme 2, a receptor to mediate the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) entry into target cells, and the cofactor transmembrane protease serine 2 were significantly upregulated in both hPSC-AECs and AOs treated with dPM2.5. In conclusion, we demonstrated the potential alveolar development toxicity and the increase of SARS-Cov-2 susceptibility of PM2.5. Our findings suggest that an hPSC-based 2D and 3D alveolar induction system could be a useful in vitro platform for evaluating the adverse effects of environmental toxins and for virus research.


Assuntos
Infecções por Coronavirus , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Pandemias , Material Particulado/toxicidade , Peptidil Dipeptidase A/genética , Células-Tronco Pluripotentes/efeitos dos fármacos , Pneumonia Viral , Betacoronavirus , Células Epiteliais/efeitos dos fármacos , Humanos , Organoides/efeitos dos fármacos , Regulação para Cima , Emissões de Veículos/toxicidade
16.
PLoS One ; 15(10): e0239338, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33085669

RESUMO

OBJECTIVES: Up to 10% of Bladder Cancers may arise following occupational exposure to carcinogens. We hypothesised that different cancer phenotypes reflected different patterns of occupational exposure. METHODS: Consecutive participants, with bladder cancer, self-completed a structured questionnaire detailing employment, tasks, exposures, smoking, lifestyle and family history. Our primary outcome was association between cancer phenotype and occupational details. RESULTS: We collected questionnaires from 536 patients, of whom 454 (85%) participants (352 men and 102 women) were included. Women were less likely to be smokers (68% vs. 81% Chi sq. p<0.001), but more likely than men to inhale environmental tobacco smoke at home (82% vs. 74% p = 0.08) and use hair dye (56% vs. 3%, p<0.001). Contact with potential carcinogens occurred in 282 (62%) participants (mean 3.1 per worker (range 0-14)). High-grade cancer was more common than low-grade disease in workers from the steel, foundry, metal, engineering and transport industries (p<0.05), and in workers exposed to crack detection dyes, chromium, coal/oil/gas by-products, diesel fumes/fuel/aircraft fuel and solvents (such as trichloroethylene). Higher staged cancers were frequent in workers exposed to Chromium, coal products and diesel exhaust fumes/fuel (p<0.05). Various workers (e.g. exposed to diesel fuels or fumes (Cox, HR 1.97 (95% CI 1.31-2.98) p = 0.001), employed in a garage (HR 2.19 (95% CI 1.31-3.63) p = 0.001), undertaking plumbing/gas fitting/ventilation (HR 2.15 (95% CI 1.15-4.01) p = 0.017), undertaking welding (HR 1.85 (95% CI 1.24-2.77) p = 0.003) and exposed to welding materials (HR 1.92 (95% CI 1.27-2.91) p = 0.002)) were more likely to have disease progression and receive radical treatment than others. Fewer than expected deaths were seen in healthcare workers (HR 0.17 (95% CI 0.04-0.70) p = 0.014). CONCLUSIONS: We identified multiple occupational tasks and contacts associated with bladder cancer. There were some associations with phenotype, although our study design precludes robust assessment.


Assuntos
Doenças Profissionais/patologia , Exposição Ocupacional/análise , Neoplasias da Bexiga Urinária/patologia , Idoso , Poluentes Ocupacionais do Ar/toxicidade , Carcinógenos/toxicidade , Estudos Transversais , Emprego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Doenças Profissionais/mortalidade , Fenótipo , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Fumar , Inquéritos e Questionários , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/mortalidade , Emissões de Veículos/toxicidade
17.
Parasitol Res ; 119(9): 2783-2798, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32683559

RESUMO

Due to the increasing consumption of platinum (Pt), especially in automobile exhaust catalysts, environmental concentrations of Pt are of emerging concern worldwide. Limited information exists on environmental concentrations, particularly in Pt mining regions, while South Africa is the world's main supplier of Pt. Moreover, other metals are also released as by-products of Pt mining, which might also cause environmental concern. Certain fish parasite taxa have the ability to accumulate metals orders of magnitude higher than their hosts and can be used to reliably detect metals with naturally low abundance. Studies on Pt accumulation in parasite-host systems are limited. Therefore, the aims of the present study were (1) to determine the accumulation of a variety of metals (cadmium (Cd), chromium (Cr), copper (Cu), nickel (Ni), lead (Pb), platinum (Pt), and zinc (Zn)) in helminth fish parasites compared with their hosts from a reference site and an impoundment impacted by Pt mining activities; (2) to assess whether there is a difference between bioaccumulation of metals in infected and uninfected hosts, as well as between hosts with different infection intensities; and (3) to compare the biomarker responses (acetylcholine esterase activity (AChE), metallothionein content (MT), catalase activity (CAT), reduced glutathione content (GSH), malondialdehyde content (MDA), protein carbonyls induction (PC), superoxide dismutase activity (SOD), and cellular energy allocation (CEA)) between infected and uninfected hosts. The cestode Atractolytocestus huronensis accumulated significantly higher concentrations of Cr, Ni, and Pt than their host Cyprinus carpio, while the nematode Contracaecum sp. accumulated significantly higher concentrations of Pt and Zn than their host Clarias gariepinus. Infected fish showed lower metal concentrations compared to uninfected fish, while the parasites had no significant effects on their hosts' biomarker responses. The parasites demonstrated the bioavailability of metals derived from Pt mining activities and their ability to resist its toxic effects. Thus, these parasites are promising sensitive accumulation indicators for Cr, Ni, Pb, and Pt contaminations from Pt mining activities.


Assuntos
Bioacumulação/fisiologia , Cestoides/química , Metais Pesados/análise , Nematoides/química , Emissões de Veículos/análise , Poluentes Químicos da Água/análise , Acetilcolinesterase/metabolismo , Animais , Cádmio/análise , Cádmio/toxicidade , Carpas/parasitologia , Catalase/metabolismo , Peixes-Gato/parasitologia , Cobre/análise , Cobre/toxicidade , Ecossistema , Monitoramento Ambiental , Glutationa/análise , Malondialdeído/análise , Metalotioneína/análise , Metais Pesados/toxicidade , Parasitos , Platina/análise , Platina/toxicidade , África do Sul , Superóxido Dismutase/metabolismo , Emissões de Veículos/toxicidade , Poluentes Químicos da Água/toxicidade
18.
Ecotoxicol Environ Saf ; 202: 110881, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32574863

RESUMO

Exposure to ambient PM2.5 may correlate with the decline of semen quality, and the underlying biological mechanism has not been fully understood. In the present study, mice were intratracheally instilled with diesel exhaust PM2.5 (DEP), and its effects on the spermatogenic process as well as the alterations of testicular gene expression profile were assessed. Our results showed that chronic exposure to DEP impaired the fertility of male mice without influencing their libido. Compared with Vehicle-exposed group, the sperm count and motility from DEP-exposed mice were significantly decreased. In addition, immunohistological staining of γH2AX and DMC1, biomarkers for meiotic double strand breaks (DSBs), demonstrated that chronic exposure to DEP comprised the repair of meiotic DSBs, thus disrupting the spermatogenesis. Deep RNA sequencing test showed altered expressions of testicular genes including the GnRH signaling pathway. In summary, our research demonstrated that chronic exposure to DEP may disrupt spermatogenesis through targeting the meiotic recombination, providing a new perspective for the research on the male reproductive system damage caused by air pollution.


Assuntos
Poluentes Atmosféricos/toxicidade , Espermatogênese/efeitos dos fármacos , Emissões de Veículos/toxicidade , Animais , Fertilidade , Masculino , Camundongos , Material Particulado/toxicidade , Análise do Sêmen , Espermatozoides/efeitos dos fármacos , Testículo
19.
PLoS One ; 15(6): e0234963, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32584832

RESUMO

Homogeneous Charge Compression Ignition (HCCI) combustion is a potential candidate for dealing with the stringent regulations on vehicle emissions while still providing very good energy efficiency. Despite the promising results obtained in preliminary studies, the lack of autoignition control has delayed its launch in the engine industry. In the development of the HCCI concept, the availability of reliable computer models has proved extremely valuable, due to their flexibility and lower cost compared with experiments using real engines. In order to obtain the best formulation of a fuel surrogate formulated with n-heptane, toluene and cyclohexane that efficiently estimate the autoignition behaviour, regression adjustments are made to the Root-Mean-Square Errors (RMSE) of experimental Starts of Combustion (SOC) from the modeled SOC. The canonical form of the Scheffé polynomials is widely used to fit the data from mixture experiments, however the experimenter might have only partial knowledge. In this paper we present the adaptation of the robust methodology for possibly misspecified blending model and an algorithm to obtain tailor-made optimal designs for mixture experiments, instead of using standard designs which are indiscriminately employed, to make good estimations of the parameters blending model. We maximize the determinant of the mean squared error matrix of the least square estimator over a realistic neighbourhood of the fitted regression mixture model. The maximized determinant is then minimized over the class of possible designs, yielding an optimal design. Thus, the computed desings are robust to the exact form of the true blending model. Standard mixture designs, as the simplex lattice, are around 25% efficient for estimation purposes compared with the designs obtained in this work when deviances from the considered model occur during the experiments. Once an optimal-robust design was selected (based on the level of certainty about model adequacy), we computed the optimal mixture that best reproduces the combustion property to be imitated. Optimal mixtures obtained when the considered model is inadequate agree with the results achieved in empirical studies, which validates the methodology proposed in this work.


Assuntos
Misturas Complexas/química , Desenho Assistido por Computador , Fontes Geradoras de Energia , Modelos Químicos , Veículos Automotores/legislação & jurisprudência , Algoritmos , Simulação por Computador , Cicloexanos/química , Heptanos/química , Tolueno/química , Emissões de Veículos/legislação & jurisprudência , Emissões de Veículos/toxicidade
20.
Environ Res ; 188: 109752, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32516633

RESUMO

Given the inconsistency of epidemiologic evidence for associations between maternal exposures to traffic-related metrics and adverse birth outcomes, this manuscript aims to provide clarity on this topic. Pooled meta-estimates were calculated using random-effects analyses. Subgroup analyses were conducted by study area, study design, and Newcastle-Ottawa quality score (NOS). Funnel plots and Egger's test were conducted to evaluate the publication bias, and Fail-safe Numbers (Fail-safe N) were measured to evaluate the robustness of models. From the initial 740 studies (last search, July 11, 2019), 26 studies were included in our analysis. The pooled odds ratio for the change in small for gestational age associated with per 500 m decrease in the distance to roads was 1.016 (95% CI: 1.004, 1.029). Subgroup analyses revealed significant positive associations between term low birth weight and traffic density in higher-quality literatures with higher NOS [1.060 (95% CI: 1.002, 1.121)], cohort studies [1.020 (95% CI: 1.006, 1.033)], and studies in North America [1.018 (95% CI: 1.005, 1.131)]. The buffer of traffic density made no difference in the effect size. Traffic density seemed to be a better indicator of traffic pollution than the distance to roads.


Assuntos
Nascimento Prematuro , Emissões de Veículos , Benchmarking , Feminino , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Veículos Automotores , América do Norte , Parto , Gravidez , Nascimento Prematuro/epidemiologia , Emissões de Veículos/toxicidade
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