Acute systemic and lung inflammation in C57Bl/6J mice after intratracheal aspiration of particulate matter from small-scale biomass combustion appliances based on old and modern technologies

Inflammation is regarded as an important mechanism behind mortality and morbidity experienced by cardiorespiratory patients exposed to urban air particulate matter (PM). Small-scale biomass combustion is an important source of particulate air pollution. In this study, we investigated association between inflammatory responses and chemical composition of PM₁ emissions from seven different small-scale wood combustion appliances representing old and modern technologies. Healthy C57Bl/6J mice were exposed by intratracheal aspiration to single dose (10?mg/kg) of particulate samples. At 4 and 18?h after the exposure, bronchoalveolar lavage fluid (BALF) as well as serum was collected for subsequent analyses of inflammatory indicators (interleukin (IL)-6, IL-1β, IL-12, and IL-10; tumor necrosis factor-α (TNF-α); keratinocyte-derived chemoattractant (KC), and interferon-γ (IFN-γ)) in multiplexing assay. When the responses to the PM₁ samples were compared on an equal mass basis, the PM from modern technology appliances increased IL-6, KC, and IL-1β levels significantly in BALF at 4 and 18?h after the exposure. In contrast, these responses were seen only at 4?h time point in serum. Increased cytokine concentrations correlated with metal-rich ash related compounds which were more predominant in the modern technology furnaces emissions. These particles induced both local and systemic inflammation. Instead, polycyclic hydrocarbon (PAH) rich PM₁ samples from old technology (OT) evoked only minor inflammatory responses. In conclusion, the combustion technology largely affects the toxicological and chemical characteristics of the emissions. The large mass emissions of old combustion technology should be considered, when evaluating the overall harmfulness between the appliances. However, even the small emissions from modern technologies may pose significant toxic risks.     

Different biological effects of PM2.5 from coal combustion,gasoline exhaust and urban ambient air relate to the PAH/metal compositions

Few studies have compared the biological effects of PM_2.5 from coal combustion, gasoline exhaust and urban ambient air, and the roles of polycyclic aromatic hydrocarbons (PAHs) and metals playing in the process remain unclear. In this study, PM_2.5 samples from coal combustion, gasoline exhaust and urban ambient air were analyzed for 16 PAHs and 23 metals. Cytotoxic and inflammatory effects of different PM_2.5 were evaluated on differentiated THP-1 and A549 cells, respectively. We found that the coal combustion PM_2.5 samples induced stronger cytotoxic and inflammatory effects (p < 0.05). Pearson’s correlation and principal component analysis showed that the PAHs containing four or more benzenoid rings and specific metals of cadmium, thallium, zinc and lead were positively related to the biological effects. Our results suggested that coal combustion PM_2.5 might be a more serious health hazard. Specific PAHs and metals might be account for the PM_2.5 induced biological effects.     

Inflammatory response and endothelial dysfunction in the hearts of mice co‐exposed to SO2, NO2, and PM2.5

SO₂, NO₂, and PM_2.5 are typical air pollutants produced during the combustion of coal. Increasing evidence indicates that air pollution has contributed to the development and progression of heart‐related diseases over the past decades. However, little experimental data and few studies of SO₂, NO₂, and PM_2.5 co‐exposure in animals exist; therefore, the relevant mechanisms underlying this phenomenon are unclear. An important characteristic of air pollution is that co‐exposure persists at a low concentration throughout a lifetime. In the present study, we treated adult mice with SO₂, NO₂, and PM_2.5 at various concentrations (0.5 mg/m³ SO₂, 0.2 mg/m³ NO₂ 6 h/d, with intranasal instillation of 1 mg/kg PM_2.5 every other day during these exposures; or 3.5 mg/m³ SO₂, 2 mg/m³ NO₂ 6 h/d, and 10 mg/kg PM_2.5 for 28 d). Blood pressure (BP), heart rate (HR), histopathological damage, and inflammatory and endothelial cytokines in the heart were assessed. The results indicate that co‐exposure caused endothelial dysfunction by elevating endothelin‐1 (ET‐1) expression and repressing the endothelial nitric oxide synthase (eNOS) level as well as stimulating the inflammatory response by increasing the levels of cyclooxygenase‐2 (COX‐2), inducible nitric oxide synthase (iNOS), tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6). Additionally, these alterations were confirmed by histological staining. Furthermore, we observed decreased BP and increased HR after co‐exposure. Our results indicate that co‐exposure to SO₂, NO₂, and PM_2.5 may be a major risk factor for cardiac disease and may induce injury to the hearts of mammals and contribute to heart disease. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1996–2005, 2016.     

The selective MMP-12 inhibitor, AS111793 reduces airway inflammation in mice exposed to cigarette smoke

BACKGROUND: Macrophage elastase (MMP-12) is involved in the inflammatory process of chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate in mice the effect of MMP-12 inhibition on the inflammatory process induced by cigarette smoke (CS) or by lipopolysaccharide (LPS) exposure of the airways. EXPERIMENTAL APPROACH: C57BL/6 mice were given, orally, either the selective MMP-12 inhibitor AS111793 (3, 10, 30 and 100 mg kg(-1)), the PDE-4 inhibitor roflumilast (3 mg kg(-1)) or vehicle, then exposed to CS (for 3 days) or to LPS (100 microg mL(-1), 30 min). Subsequent to the last smoke or LPS exposure, bronchoalveolar lavages (BAL) were performed and lungs were removed and homogenized to analyze various markers of inflammation at appropriate times. KEY RESULTS: Inhibition of MMP-12 by AS111793 (10 and 30 mg kg(-1)) was associated with a reduction of the increase in neutrophil number in BAL fluids after 4 days and of macrophages after 11 days. On day 4, AS111793 also significantly reduced all the inflammation markers that had increased after CS exposure, including soluble TNF receptors I and II, MIP-1gamma, IL-6 and pro-MMP-9 activity in BAL fluids, and KC/CXCL1, fractalkine/CX3CL1, TIMP-1 and I-TAC/CXCL11 in lung parenchyma. In contrast, inhibition of MMP-12 did not reduce neutrophil influx, pro-MMP-9 activity or KC/CXCL1 release in BAL fluids of mice exposed to LPS. CONCLUSION: Inhibition of MMP-12 with AS111793, reduced the inflammatory process associated with exposure of mice to CS, strongly suggesting a specific involvement of MMP-12 in lung inflammation following CS exposure.     

Synergistic effect of carbon nuclei and polyaromatic hydrocarbons on respiratory and immune responses

Particulate matter with aerodynamic diameter ≤2.5 μm (PM_2.5) is generally composed of carbon nuclei associated with various organic carbons, metals, ions and biological materials. Among these components, polyaromatic hydrocarbons (PAHs) such as benzo(a)pyrene (BaP) and quinones have detrimental effects on airway epithelial cells and immunodisrupting effects, which leads to the exacerbation of respiratory allergies. The effects of PAHs and the carbon nuclei, separately as well as in combination, remain to be established. We investigated the effects of BaP, 9,10‐phenanthroquinone (9,10‐PQ), and 1,2‐napthoquinone (1,2‐NQ) and their combined effects with heated diesel exhaust particle (H‐DEP) as carbon nuclei of typical PM_2.5. We exposed human airway epithelial cells (BEAS‐2B), murine bone marrow‐derived antigen‐presenting cells (APCs), and murine splenocytes to BaP, 9,10‐PQ, or 1,2‐NQ in the presence and absence of H‐DEP. Several important inflammatory cytokines and cell surface molecules were measured. PAHs alone did not have apparent cytotoxic effects on BEAS‐2B, whereas combined exposure with H‐DEP induced noticeable detrimental effects which mainly reflected the action of H‐DEP itself. BaP increased CD86 expression as an APC surface molecule regardless of the presence or absence of H‐DEP. None of the BaP, 9,10‐PQ, or 1,2‐NQ exposure alone or their combined exposure with H‐DEP resulted in any significant activation of splenocytes. These results suggest that PAHs and carbon nuclei show additive effects, and that BaP with the carbon nuclei may contribute to exacerbations of allergic respiratory diseases including asthma by PM_2.5, especially via antigen‐presenting cell activation.     

Heterogeneities in Inflammatory and Cytotoxic Responses of RAW 264.7 Macrophage Cell Line to Urban Air Coarse,Fine, and Ultrafine Particles From Six European Sampling Campaigns

We investigated the cytotoxic and inflammatory activities of size-segregated particulate samples (particulate matter, PM) from contrasting air pollution situations in Europe. Coarse (PM_10?2.5), fine (PM_2.5?0.2), and ultrafine (PM_0.2) particulate samples were collected with a modified Harvard high-volume cascade impactor (HVCI). Mouse RAW 264.7 macrophages were exposed to the samples for 24 h. Selected inflammatory mediators, nitric oxide (NO) and cytokines (tumor necrosis factor alpha [TNFα], interleukin 6 [IL-6], macrophage inflammatory protein-2 [MIP-2]), were measured together with cytotoxicity (MTT test), and analysis of apoptosis and cell cycle (propidium iodide staining). The PM_10?2.5 samples had a much higher inflammatory activity than the PM_2.5?0.2 and PM_0.2 samples, but the PM_2.5?0.2 samples showed the largest differences in inflammatory activity, and the PM_0.2 samples in cytotoxicity, between the sampling campaigns. The PM_2.5?0.2 samples from traffic environments in springtime Barcelona and summertime Athens had the highest inflammatory activities, which may be related to the high photochemical activity in the atmosphere during the sampling campaigns. The PM_0.2 sample from wintertime Prague with proven impacts from local coal and biomass combustion had very high cytotoxic and apoptotic activities and caused a distinct cell cycle arrest. Thus, particulate size, sources, and atmospheric transformation processes affect the toxicity profile of urban air particulate matter. These factors may explain some of the heterogeneity observed in particulate exposure-response relationships of human health effects in epidemiological studies.     

Involvement of EGF receptor signaling and NLRP12 inflammasome in fine particulate matter‐induced lung inflammation in mice

Epidemiological studies have shown that exposure to ambient fine particulate matter (PM_2.5) is associated with respiratory diseases. Lung inflammation is a central feature of many pulmonary diseases, which can be induced by PM_2.5 exposure. However, the mechanisms underlying PM_2.5‐induced lung inflammation remain unclear. To characterize the role of epidermal growth factor receptor (EGFR) and inflammasome in PM_2.5‐induced lung inflammation in mice, 30 BALB/c mice were intrabroncheally instilled with saline and PM_2.5 suspension (4.0 mg/kg b.w.) for 5 consecutive days, respectively. Bronchoalveolar lavage (BAL) was conducted and BAL fluid (BALF) was collected. The levels of reactive oxygen species (ROS), inducible nitric oxide synthase (iNOS), epidermal growth factor (EGF), CXCL1, interleukin (IL)?1β, and IL‐18 in BALF were determined using ELISA. mRNA levels of IL‐6, IL‐1β, IL‐18, CXCL1, IL‐10, NLRP3, Caspase‐1, and NLRP12 in lung tissues were determined by RT‐PCR. Phospho‐EGFR (Tyr1068) and phospho‐Akt (Thr308) in lung tissues were examined using immunohistochemical staining and Western blotting, respectively. Protein levels of Caspase‐1, NLRP3, NF‐κB‐p52/p100, and NF‐κB‐p65 in bronchial epithelium were examined using immunohistochemical staining. It was shown that PM_2.5 exposure induced lung inflammation. Levels of total protein, ROS, iNOS, EGF, and CXCL1 and cell number in the BALF of mice exposed to PM_2.5 were markedly elevated relative to the control. mRNA levels of CXCL1, IL‐1β, and IL‐18 in lung tissues of PM_2.5‐exposed mice were increased in comparison with the control. However, level of NLRP12 mRNA in lung tissues of PM_2.5‐exposed mice was reduced. Phospho‐EGFR (Tyr1068) and phospho‐Akt (Thr308) levels in the lungs of PM_2.5‐instilled mice were higher than those in the lungs of the control. The protein levels of NF‐κB‐p52/p100 and NF‐κB‐p65 in bronchial epithelium of PM_2.5‐exposed mice were also increased compared with the control. This study suggests that EGF‐EGFR‐Akt‐NF‐κB signaling and NLRP12 inflammasome may be associated with PM_2.5‐induced lung inflammation in mice. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1121–1134, 2017.     

Associations of urban air particulate composition with inflammatory and cytotoxic responses in RAW 246.7 cell line

Epidemiological studies show heterogeneities in the particulate pollution-related exposure–effect relationships among cardiorespiratory patients, but the connection to chemical composition and toxic properties of the inhaled particles is largely unknown. To identify the chemical constituents and sources responsible for the diverse inflammatory and cytotoxic effects of urban air, fine (PM_2.5–0.2) and coarse (PM_10–2.5) particulate samples were collected during contrasting air pollution situations. We exposed mouse RAW 246.7 macrophages for 24?hrs to PM_2.5–0.2 and PM_10–2.5 samples from six European cities. The concentrations of proinflammatory cytokines (IL-6, TNFα), chemokine (MIP-2), and nitric oxide were measured from the cell culture medium, and the cytotoxicity was assayed. Spearman’s correlations between the chemical constituents and cellular responses were analyzed. In the PM_2.5–0.2 size range, the tracers of photo-oxidation of organics in the atmosphere (oxalate, succinate, malonate), some transition metals (Ni, V, Fe, Cu, Cr), and insoluble soil constituents (Ca, Al, Fe, Si) correlated positively with the response parameters. In contrast, the tracers of incomplete biomass (monosaccharide anhydrides) and coal (As) combustion, and polycyclic aromatic hydrocarbons (PAHs), had negative correlations with the inflammatory activity. The compositions of PM_10–2.5 samples were more uniform and there were only occasional high correlations between the chemical constituents, endotoxin, and the response parameters. The present results suggest that the local sources of incomplete combustion and resuspended road dust are important producers of harmful fine particulate constituents that may, however, operate via diverse toxicity mechanisms. The results agree well with our recent findings in the mouse lung.     

Inflammation and tissue damage in mouse lung by single and repeated dosing of urban air coarse and fine particles collected from six European cities

The authors have previously demonstrated heterogeneities in the inflammatory activities of urban air fine (PM_2.5–0.2) and coarse (PM_10–2.5) particulate samples collected from six European cities with contrasting air pollution situations. The same samples (10?mg/kg) were intratracheally instilled to healthy C57BL/6J mice either once or repeatedly on days 1, 3, and 6 of the study week. The lungs were lavaged 24?h after the single dose or after the last repeated dosing. In both size ranges, repeated dosing of particles increased the total cell number in bronchoalveolar lavage fluid (BALF) more than the respective single dose, whereas cytokine concentrations were lower after repeated dosing. The lactate dehydrogenase (LDH) responses increased up to 2-fold after repeated dosing of PM_2.5–0.2 samples and up to 6-fold after repeated dosing of PM_10–2.5 samples. PM_10–2.5 samples evoked a more extensive interstitial inflammation in the mouse lungs. The constituents with major contributions to the inflammatory responses were oxidized organic compounds and transition metals in PM_2.5–0.2 samples, Cu and soil minerals in PM_10–2.5 samples, and Zn in both size ranges. In contrast, poor biomass and coal combustion were associated with elevated levels of polycyclic aromatic hydrocarbons (PAHs) and a consistent inhibitory effect on the inflammatory activity of PM_2.5–0.2 samples. In conclusion, repeated intratracheal instillation of both fine and coarse particulate samples evoked enhanced pulmonary inflammation and cytotoxicity compared to single-dose administration. The sources and constituents of urban air particles responsible for these effects appear to be similar to those encountered in the authors’ previous single-dose study.     

Efficiency of log wood combustion affects the toxicological and chemical properties of emission particles

Context: Particulate matter (PM) has been identified as a major environmental pollutant causing severe health problems. Large amounts of the harmful particulate matter (PM) are emitted from residential wood combustion, but the toxicological properties of wood combustion particles are poorly known.

Objective: To investigate chemical and consequent toxicological characteristics of PM₁ emitted from different phases of batch combustion in four heating appliances.

Materials and methods: Mouse RAW264.7 macrophages and human BEAS-2B bronchial epithelial cells were exposed for 24 h to different doses (15–300 µg/mL) of wood combustion particles. After the exposure, cytotoxicity, genotoxicity, production of the inflammatory mediators (TNF-α and MIP-2) and effects on the cell cycle were assessed. Furthermore, the detected toxicological responses were compared with the chemical composition of PM₁ samples including PAHs, metals and ions.

Results: All the wood combustion samples exerted high cytotoxicity, but only moderate inflammatory activity. The particles emitted from the inefficient phase of batch combustion in the sauna stove (SS) induced the most extensive cytotoxic and genotoxic responses in mammalian cells. Polycyclic aromatic hydrocarbons (PAHs) and other organic compounds in PM₁ samples might have contributed to these effects. Instead, water-soluble metals seemed to participate in the cytotoxic responses triggered by the particles from more efficient batch combustion in the masonry heaters. Overall, the toxicological responses were decreased when the combustion phase was more efficient.

Conclusion: Efficiency of batch combustion plays a significant role in the harmfulness of PM even under incomplete wood combustion processes.     

Dose and Time Dependency of Inflammatory Responses in the Mouse Lung to Urban Air Coarse,Fine, and Ultrafine Particles From Six European Cities

We investigated the dose and time dependency of inflammatory and cytotoxic responses to size-segregated urban air particulate samples in the mouse lung. Coarse (PM_10?2.5), fine (PM_2.5?0.2), and ultrafine (PM_0.2) particles were collected in six European cities (Duisburg, Prague, Amsterdam, Helsinki, Barcelona, Athens) in selected seasons using a modified Harvard high-volume cascade impactor. Healthy C57Bl/6J mice were intratracheally exposed to the particulate samples in a 24-h dose-response study (1, 3, and 10 mg/kg) and in 4-, 12-, and 24-h time course studies (10 mg/kg). After the exposures, the lungs were lavaged and the bronchoalveolar lavage fluid (BALF) was assayed for indicators of inflammation and tissue damage: total cell number, cell differential, total protein, and lactate dehydrogenase (LDH) and cytokine (tumor necrosis alpha [TNF-α], interleukin-6 [IL-6], and keratinocyte-derived chemokine [KC]) concentrations. In general, PM_10?2.5 samples had higher inflammatory activity than PM_2.5?0.2 samples. PM_0.2 samples showed negligible inflammatory activity. PM_10?2.5 and PM_2.5?0.2 samples caused large increases in BALF cytokine concentrations at 4 h, but not at 12 or 24 h, after exposure. The BALF total cell number and total protein concentrations increased significantly at 12 h for both the PM_10?2.5 and PM_2.5?0.2 samples, but only PM_10?2.5 samples produced consistent, significant increases at 24 h after exposure. There was more heterogeneity in BALF cytokine and neutrophil cell number responses to PM_2.5?0.2 samples than to PM_10?2.5 samples between the sampling campaigns. Thus, particle size, sources, and atmospheric transformation processes affect the inflammatory activity and response duration of urban air particulate matter in the mouse lung.     

Chemical Compositions Responsible for Inflammation and Tissue Damage in the Mouse Lung by Coarse and Fine Particulate Samples from Contrasting Air Pollution in Europe

Inflammation is regarded as an important mechanism in mortality and morbidity associated with exposures of cardiorespiratory patients to urban air particulate matter. We investigated the association of the chemical composition and sources of urban air fine (PM_2.5?0.2) and coarse (PM_10?2.5) particulate samples with the inflammatory activity in the mouse lung. The particulate samples were collected during selected seasons in six European cities using a high-volume cascade impactor. Healthy C57BL/6J mice were intratracheally instilled with a single dose (10 mg/kg) of the particulate samples. At 4, 12, and 24 h after the exposure, the lungs were lavaged and the bronchoalveolar lavage fluid (BALF) was assayed for indicators of inflammation and tissue damage: cell number, total protein, and cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-6, and KC). Dicarboxylic acids and transition metals, especially Ni and V, in PM_2.5?0.2 correlated positively and some secondary inorganic ions (NO₃^-, NH₄⁺) negatively with the inflammatory activity. Total organic matter and SO₄^2- had no consistent correlations. In addition, the soil-derived constituents (Ca²⁺, Al, Fe, Si) showed positive correlations with the PM_2.5?0.2-induced inflammatory activity, but their role in PM_10?2.5 remained obscure, possibly due to largely undefined biogenic material. Markers of poor biomass and coal combustion, i.e., monosaccharide anhydrides and As, were associated with elevated PAH contents in PM_2.5?0.2 and a consistent immunosuppressive effect. Overall, our results support epidemiological findings that the local sources of incomplete combustion and resuspended road dust are important in urban air particulate pollution-related health effects.     

The effects of ambient particulate matter on human adipose tissue

ABSTRACT

The effects of particulate matter (PM) air pollution on adipose tissue have mainly been studied in animal models. The aim of this study was to examine the potential associations between PM exposure and 25 cellular markers in human omental (OM) and subcutaneous (SC) adipose tissue. The PM exposure assessments for both PM_2.5 (PM <2.5 μm in diameter) and PM₁₀ (<10 μm) were based upon a novel hybrid satellite-based spatio-temporally resolved model. We calculated the PM exposure above the background threshold for 1 week (acute phase), 3 and 6 months (intermediate phase), and 1 year (chronic phase) prior to tissue harvesting and tested the associations with adipose cell metabolic effects using multiple linear regressions and heat maps strategy. Chemokine levels were found to increase after acute and intermediate exposure duration to PM₁₀. The levels of stress signaling biomarkers in the SC and OM tissues rose after acute exposure to PM₁₀ and PM_2.5. Macrophage and leucocyte counts were associated with severity of PM exposure in all three duration groups. Adipocyte diameter decreased in all exposure periods. Our results provide evidence for significant contribution of air pollutants exposure to adipose tissue inflammation as well as for pathophysiological mechanisms of metabolic dysregulation that may be involved in the observed responses.     

Experimental Exposure to Wood-Smoke Particles in Healthy Humans: Effects on Markers of Inflammation,Coagulation, and Lipid Peroxidation

Particulate air pollution is known to increase cardiovascular morbidity and mortality. Proposed mechanisms underlying this increase include effects on inflammation, coagulation factors, and oxidative stress, which could increase the risk of coronary events and atherosclerosis. The aim of this study was to examine whether short-term exposure to wood smoke affects markers of inflammation, blood hemostasis, and lipid peroxidation in healthy humans. Thirteen subjects were exposed to wood smoke and clean air in a chamber during two 4-h sessions, 1 wk apart. The mass concentrations of fine particles at wood smoke exposure were 240–280 μg/m³, and number concentrations were 95,000–180,000/cm³. About half of the particles were ultrafine (< 100 nm). Blood and urine samples were taken before and after the experiment. Exposure to wood smoke increased the levels of serum amyloid A, a cardiovascular risk factor, as well as factor VIII in plasma and the factor VIII/von Willebrand factor ratio, indicating a slight effect on the balance of coagulation factors. Moreover, there was an increased urinary excretion of free 8-iso-prostaglandin_2α, a major F₂-isoprostane, though this was based on nine subjects only, indicating a temporary increase in free radical-mediated lipid peroxidation. Thus, wood-smoke particles at levels that can be found in smoky indoor environments seem to affect inflammation, coagulation, and possibly lipid peroxidation. These factors may be involved in the mechanisms whereby particulate air pollution affects cardiovascular morbidity and mortality. The exposure setup could be used to establish which particle characteristics are critical for the effects.     

Changes in Lung Function and Airway Inflammation Among Asthmatic Children Residing in a Woodsmoke-Impacted Urban Area

Fine particulate matter (PM_2.5) is associated with respiratory effects, and asthmatic children are especially sensitive. Preliminary evidence suggests that combustion-derived particles play an important role. Our objective was to evaluate effect estimates from different PM_2.5 exposure metrics in relation to airway inflammation and lung function among children residing in woodsmoke-impacted areas of Seattle. Nineteen children (ages 6–13 yr) with asthma were monitored during the heating season. We measured 24-h outdoor and personal concentrations of PM_2.5 and light-absorbing carbon (LAC). Levoglucosan (LG), a marker of woodsmoke, was also measured outdoors. We partitioned PM_2.5 exposure into its ambient-generated (E_ag) and nonambient (E_na) components. These exposure metrics were evaluated in relation to daily changes in exhaled nitric oxide (FE_NO), a marker of airway inflammation, and four lung function measures: midexpiratory flow (MEF), peak expiratory flow (PEF), forced expiratory volume in the first second (FEV₁), and forced vital capacity (FVC). E_ag, but not E_na, was correlated with combustion markers. Significant associations with respiratory health were seen only among participants not using inhaled corticosteroids. Increases in FE_NO were associated with personal PM_2.5, personal LAC, and E_ag but not with ambient PM_2.5 or its combustion markers. In contrast, MEF and PEF decrements were associated with ambient PM_2.5, its combustion markers, and E_ag, but not with personal PM_2.5 or personal LAC. FEV₁ was associated only with ambient LG. Our results suggest that lung function may be especially sensitive to the combustion-generated component of ambient PM_2.5, whereas airway inflammation may be more closely related to some other constituent of the ambient PM_2.5 mixture.     

Effects of organic chemicals from diesel exhaust particles on adipocytes differentiated from human mesenchymal stem cells

Exposure to fine particulate matter (PM_2.5) from incomplete fossil fuel combustion (coal, oil, gas and diesel) has been linked to increased morbidity and mortality due to metabolic diseases. PM_2.5 exaggerate adipose inflammation and insulin resistance in mice with diet-induced obesity. Here, we elucidate the hypothesis that such systemic effects may be triggered by adhered particle components affecting adipose tissue directly. Studying adipocytes differentiated from primary human mesenchymal stem cells, we found that lipophilic organic chemicals (OC) from diesel exhaust particles induced inflammation-associated genes and increased secretion of the chemokine CXLC8/interleukin-8 as well as matrix metalloprotease 1. The oxidative stress response gene haem oxygenase-1 and tumour necrosis factor alpha were seemingly not affected, while aryl hydrocarbon receptor-regulated genes, cytochrome P450 1A1 (CYP1A1) and CYP1B1 and plasminogen activator inhibitor-2, were clearly up-regulated. Finally, expression of β-adrenergic receptor, known to regulate adipocyte homoeostasis, was down-regulated by exposure to these lipophilic OC. Our results indicate that low concentrations of OC from combustion particles have the potential to modify expression of genes in adipocytes that may be linked to metabolic disease. Further studies on mechanisms linking PM exposure and metabolic diseases are warranted.     

Changes of respiratory system in mice exposed to PM4.0 or TSP from exhaust gases of combustion of cashew nut shell

Air pollution is a topic discussed all over the world and the search for alternatives to reduce it is of great interest to many researchers. The use of alternative energy sources and biofuels seems to be the environmentally safer solution. In this work, the deleterious effects on the respiratory system of mice exposed to PM_4.0 or TSP, present in exhaust gases from the combustion of CNS were investigated, through data from respiratory system mechanics, oxidative stress, histopathology and morphometry of the parenchyma pulmonary. The results show changes in all variables of respiratory system mechanics, in oxidative stress, the histopathological analysis and lung morphometry. The results provide experimental support for epidemiological observations of association between effects on the respiratory system and exposure to PM_4.0 or TSP from CNS combustion exhaust gases, even at acute exposure. It can serve as a basis for regulation or adjustment of environmental laws that control the emissions of these gases.     

Respiratory symptoms,lung function decrement and chronic obstructive pulmonary disease in pre-menopausal Indian women exposed to biomass smoke

Abstract

Background: The impact of chronic exposure to smoke from biomass burning on respiratory health has been examined.

Methods: Six-hundred and eighty-one non-smoking women (median age 35 years) from eastern India who cook exclusively with biomass (wood, dung and crop residues) and 438 age-matched women from similar neighborhood who cook with liquefied petroleum gas (LPG) were examined. Pulmonary function test was done by spirometry. The concentrations of particulate matter having diameter of < 10?µm (PM₁₀) and < 2.5?µm (PM_2.5) in indoor air was measured by real-time aerosol monitor.

Results: Compared with LPG users, biomass users had greater prevalence of upper (50.9 versus 28.5%) and lower respiratory symptoms (71.8 versus 30.8%) and dyspnea (58.4 versus 19.9%). They showed reduction in all parameters measured by spirometer especially in mid-expiratory volume. PM₁₀ and PM_2.5 concentration in biomass using kitchen were 2–3-times more than LPG-using kitchen, and the decline in spirometry values was positively associated PM₁₀ and PM_2.5 levels in indoor air after controlling education, family income and kitchen location as potential confounders. Overall, 29.7% of biomass users and 16.4% of LPG users had deficient lung function, and restrictive type of deficiency was predominant. Chronic obstructive pulmonary disease (COPD) was diagnosed in 4.6% of biomass and 0.9% of LPG users. Women who predominantly used dung cake and did not possess separate kitchen had poorer lung function.

Conclusion: Cumulative exposure to biomass smoke causes lung function decrement and facilitates COPD development even in non-smoking and relatively young pre-menopausal women.     

Resveratrol relieves particulate matter (mean diameter < 2.5 μm)‐induced oxidative injury of lung cells through attenuation of autophagy deregulation

Oxidative stress and inflammation are critically implicated in ambient fine particulate matter (mean diameter < 2.5 μm; PM_2.5)‐induced lung injury. Autophagy, playing a crucial role in various physiopathological conditions, modulates cellular homeostasis and stress adaptation. Resveratrol is a phytoalexin that exerts potent antioxidant effects on cardiopulmonary diseases. To date, the mechanisms by which resveratrol protects against PM_2.5 remain to be elucidated. In the present study, we investigated the effect of resveratrol on PM_2.5‐induced oxidative injury. The potential role of nuclear factor erythroid‐2‐related factor 2 and autophagy in this progress was explored. Human bronchial epithelial cells were treated with PM_2.5 and the cytotoxicity and oxidative stress markers were determined. The results showed that PM_2.5 decreased cell viability and elevated the level of lactate dehydrogenase. The levels of malondialdehyde and reactive oxygen species were increased by PM_2.5 exposure. PM_2.5 also induced a significant increase of the inflammatory cytokines including interleukin (IL)‐6, IL‐8, IL‐1β and tumor necrosis factor α. Meanwhile, PM_2.5 triggered autophagy formation and alteration of the nuclear factor erythroid‐2‐related factor 2 pathway. Furthermore, human bronchial epithelial cells were co‐treated with PM_2.5 and resveratrol in the presence or absence of 3‐methylamphetamine, an inhibitor of autophagic formation. It was revealed that resveratrol intervention abolished PM_2.5‐induced oxidative injury partially through the suppression of autophagy deregulation. Findings from this study could provide new insights into the molecular mechanisms of pulmonary intervention during PM_2.5 exposure.     

Application of the margin-of-exposure (MoE) approach to substances in food that are genotoxic and carcinogenic e.g.: Benzo[a]pyrene and polycyclic aromatic hydrocarbons

Benzo[a]pyrene (BaP) and a number of other polycyclic aromatic hydrocarbons (PAH) are mutagenic and are also carcinogenic in rodent bioassays. Oral carcinogenicity data are not available for individual PAH other than BaP, and so BaP has been used as a marker of the carcinogenicity of, and exposure to, PAHs. Carcinogenicity studies of coal tar mixtures, considered to be representative of the genotoxic and carcinogenic PAH in food, have been used for dose-response modelling. Modelling the number of tumour-bearing mice resulted in a BMDL₁₀ of 0.122 mg BaP/kg-bw/day, which was lower than that for any of the individual tumours and was considered to be most appropriate since the different PAH may have different mechanisms of carcinogenicity. An average dietary exposure estimates of 0.008 μg BaP/kg-bw/day was identified from the range of national estimates. The calculated MoE was 15,000.