Nrf2 is an important transcription factor implicated in the oxidative stress response, which has been reported to play an important role in the way by which air pollution particulate matter (PM2.5) ...induces adverse health effects. This study investigates the mechanism by which Nrf2 exerts its protective effect in PM2.5 induced toxicity in lung cells. Lung cells silenced for Nrf2 (shNrf2) demonstrated diverse susceptibility to various PM extracts; water extracts containing high levels of dissolved metals exhibited higher capacity to generate mitochondrial reactive oxygen species (ROS) and hence increased oxidative stress levels. Organic extracts containing high levels of polycyclic aromatic hydrocarbons (PAHs) increased mortality and reduced ROS production in the silenced cells. shNrf2 cells exhibited a higher basal mitochondrial respiration rate compared to the control cells. Following exposure to water extracts, the mitochondrial respiration increased, which was not observed with the organic extracts. shNrf2 cells exposed to the organic extracts showed lower mitochondrial membrane potential and lower mtDNA copy number. Nrf2 may act as a signaling mediator for the mitochondria function following PM2.5 exposure.
Display omitted
•Nrf2 has a crucial role in PM2.5 induced toxicity.•PAHs and metals possess different toxicity mechanisms.•Nrf2 affects the mitochondrial membrane potential.•Metals from PM2.5 may act as uncouplers.
Exposure to air pollution can induce oxidative stress, inflammation and adverse health effects. To understand how seasonal and chemical variations drive health impacts, we investigated indications ...for oxidative stress and inflammation in mice exposed to water and organic extracts from urban fine particles/PM2.5 (particles with aerodynamic diameter ≤ 2.5 μm) collected in Beijing, China. Higher levels of pollution components were detected in heating season (HS, winter and part of spring) PM2.5 than in the non-heating season (NHS, summer and part of spring and autumn) PM2.5. HS samples were high in metals for the water extraction and high in polycyclic aromatic hydrocarbons (PAHs) for the organic extraction compared to their controls. An increased inflammatory response was detected in the lung and liver following exposure to the organic extracts compared to the water extracts, and mostly in the HS PM2.5. While reduced antioxidant response was observed in the lung, it was activated in the liver, again, more in the HS extracts. Nrf2 transcription factor, a master regulator of stress response that controls the basal oxidative capacity and induces the expression of antioxidant response, and its related genes were induced. In the liver, elevated levels of lipid peroxidation adducts were measured, correlated with histologic analysis that revealed morphologic features of cell damage and proliferation, indicating oxidative and toxic damage. In addition, expression of genes related to detoxification of PAHs was observed. Altogether, the study suggests that the acute effects of PM2.5 can vary seasonally with stronger health effects in the HS than in the NHS in Beijing, China and that some secondary organs may be susceptible for the exposure damage. Specifically, the liver is a potential organ influenced by exposure to organic components such as PAHs from coal or biomass burning and heating.
Display omitted
•Extracts from PM collected in Beijing harm the lung and liver.•Extracts of collected heating season (HS)-PM contained higher levels of metals and Poly aromatic hydrocarbons (PAH) than the non-HS extracts.•In the lungs, the organic extracts increased oxidative damage and reduced protection mechanisms.•In the liver, exposure to organic extracts increased Nrf2 protection genes.•PAH from coal and biomass burning may lead to observed damage in the liver.
Inhalation of traffic-associated atmospheric particulate matter (PM2.5) is recognized as a significant health risk. In this study, we focused on a single (“subclinical response”) exposure to ...water-soluble extracts from PM collected at a roadside site in a major European city to elucidate potential components that drive pulmonary inflammatory, oxidative, and defense mechanisms and their systemic impacts. Intratracheal instillation (IT) of the aqueous extracts induced a 24 h inflammatory response characterized by increased broncho-alveolar lavage fluid (BALF) cells and cytokines (IL-6 and TNF-α), increased reactive oxygen species production, but insignificant lipids and proteins oxidation adducts in mouse lungs. This local response was largely self-resolved by 48 h, suggesting that it could represent a subclinical response to everyday-level exposure. Removal of soluble metals by chelation markedly diminished the pulmonary PM-mediated response. An artificial metal solution (MS) recapitulated the PM extract response. The self-resolving nature of the response is associated with activating defense mechanisms (increased levels of catalase and glutathione peroxidase expression), observed with both PM extract and MS. In conclusion, metals present in PM collected near roadways are largely responsible for the observed transient local pulmonary inflammation and oxidative stress. Simultaneous activation of the antioxidant defense response may protect against oxidative damage.
Exposure to particulate matter (PM) pollution in cities and urban canyons can be harmful to the exposed population. However, the underlying mechanisms that lead to health effects are not yet ...elucidated. It is postulated that exposure to repeated, small, environmentally relevant concentrations can affect lung homeostasis. This study examines the impact of repeated exposures to urban PM on mouse lungs with focus on inflammatory and oxidative stress parameters. Aqueous extracts from collected urban PM were administered to mice by 5 repeated intra-tracheal instillations (IT). Multiple exposures, led to an increase in cytokine levels in both bronchoalveolar lavage fluid and in the blood serum, indicating a systemic reaction. Lung mRNA levels of antioxidant/phase II detoxifying enzymes decreased by exposure to the PM extract, but not when metals were removed by chelation. Finally, disruption of lung tissue oxidant-inflammatory/defense balance was evidenced by increased levels of lipid and protein oxidation. Unlike response to a single IT exposure to the same dose and source of extract, multiple exposures result in lung oxidative damage and a systemic inflammatory reaction. These could be attributed to compromised capacity to activate the protective Nrf2 tissue defense system. It is suggested that water-soluble metals present in urban PM, potentially from break and tire wear, may constitute major drivers of the pulmonary and systemic responses to multiple exposure to urban PM.
•Repeated exposure to urban PM cause systemic inflammation and oxidative damage to lung tissue lipids and proteins.•Repeated exposure to these PM extracts decreased transcription of Nrf2 protective genes.•Single as opposed to repeated exposure, induced confined lung response accompanied by activated defense mechanisms.•Metals, potentially from break and tire wear, drive the pulmonary response with exposure to urban PM.
Repeated exposures to urban PM water extracts resulted in systemic inflammation and oxidative damage accompanied by decreased expression of Nrf2 protective gene targets in mice lungs.
Humic-like substances (HULIS) account for a major redox-active fraction of biomass burning organic aerosols (BBOA). During atmospheric transport, fresh acidic BB-HULIS in droplets and humid aerosols ...are subject to neutralization and pH-modified aging process. In this study, solutions containing HULIS isolated from wood smoldering emissions were first adjusted with NaOH and NH3 to pH values in the range of 3.6–9.0 and then aged under oxic dark conditions. Evolution of HULIS oxidative potential (OP) and total peroxide content (equivalent H2O2 concentration, H2O2eq) were measured together with the changes in solution absorbance and chemical composition. Notable immediate responses such as peroxide generation, HULIS autoxidation, and an increase in OP and light absorption were observed under alkaline conditions. Initial H2O2eq, OP, and absorption increased exponentially with pH, regardless of the alkaline species added. Dark aging further oxidized the HULIS and led to pH-dependent toxic and chemical changes, exhibiting an alkaline-facilitated initial increase followed by a decrease of OP and H2O2eq. Although highly correlated with HULIS OP, the contributions of H2O2eq to OP are minor but increased both with solution pH and dark aging time. Alkalinity-assisted autoxidation of phenolic compounds and quinoids with concomitant formation of H2O2 and other alkalinity-favored peroxide oxidation reactions are proposed here for explaining the observed HULIS OP and chemical changes in the dark. Our findings suggest that alkaline neutralization of fresh BB-HULIS represents a previously overlooked peroxide source and pathway for modifying aerosol redox-activity and composition. Additionally, these findings imply that the lung fluid neutral environment can modify the OP and peroxide content of inhaled BB-HULIS. The results also suggest that common separation protocols of HULIS using base extraction methods should be treated with caution when evaluating and comparing their composition, absorption, and relative toxicity.
Display omitted
•pH plays a crucial role in determining fresh BB-HULIS characters•Light absorption, OP, and peroxide yield of fresh BB-HULIS increase exponentially with solution pH•Increase solution alkalinity promotes BB-HULIS autoxidation and facilitates OP and peroxides changes in dark aging•Alkalinity-assisted autoxidation of BB-HULIS in lung fluid represents potential health hazard
•Carbonyl compounds dominated semivolatile compounds in SOA.•Hydroxyl radical oxidation SOA bear a low oxidative potential and weak cytotoxicity.•Hydroxyl radical oxidation increases light absorption ...and decreases scattering of SOA.•Airborne SOA induces a cooling effect.
Biomass burning (BB) is an important source of primary organic aerosols (POA). These POA contain a significant fraction of semivolatile organic compounds, and can release them into the gas phase during the dilution process in transport. Such evaporated compounds were termed “secondarily evaporated BB organic gases (SBB-OGs)” to distinguish them from the more studied primary emissions. SBB-OGs contribute to the formation of secondary organic aerosols (SOA) through reactions with atmospheric oxidants, and thus may influence human health and the Earth's radiation budget. In this study, tar materials collected from wood pyrolysis were taken as proxies for POA from smoldering-phase BB and were used to release SBB-OGs constantly in the lab. OH-initiated oxidation of the SBB-OGs in the absence of NOx was investigated using an oxidation flow reactor, and the chemical, optical, and toxicological properties of SOA were comprehensively characterized. Carbonyl compounds were the most abundant species in identified SOA species. Human lung epithelial cells exposed to an environmentally relevant dose of the most aged SOA did not exhibit detectable cell mortality. The oxidative potential of SOA was characterized with the dithiothreitol (DTT) assay, and its DTT consumption rate was 15.5 ± 0.5 pmol min−1 μg−1. The SOA present comparable light scattering to BB-POA, but have lower light absorption with imaginary refractive index less than 0.01 within the wavelength range of 360–600 nm. Calculations based on Mie theory show that pure airborne SOA with atmospherically relevant sizes of 50–400 nm have a cooling effect; when acting as the coating materials, these SOA can counteract the warming effect brought by airborne black carbon aerosol.
Adverse health effects due to exposure to particulate matter (PM) are among the most important global environmental health risks. However, the effects of exposure to secondary organic aerosols (SOA), ...a major component of the global aerosol, are largely unknown. Here we exposed lung epithelial cells (A549) to fresh and aged SOA particles and investigated the effect of SOA atmospheric aging on cell viability and gene expression. Naphthalene- and α-pinene-derived SOA were formed in an oxidation flow reactor that simulates atmospheric SOA formation and aging dominated by OH radical oxidation under NO x -free conditions. The SOA mass and chemical composition were characterized on-line using a scanning mobility particle sizer and aerosol mass spectrometer. Fresh and aged SOA were directed to an air–liquid interface cell exposure system. Aged naphthalene- and α-pinene-derived SOA were somewhat more toxic than fresh SOA. Aged naphthalene SOA contained peroxide levels that were higher than those of fresh SOA. The level of induction of Nrf2 signaling increased following exposure to aged naphthalene SOA. Given the global prevalence of SOA and its observed toxicity, this study calls for more studies aimed at understanding the underlying mechanics.
Display omitted
•A comprehensive comparison between SOANap-SP and SOAβPin-SP shows differences in their chemical composition.•SOANap-SP has a higher cytotoxic potential than SOAβPin-SP.•SOANap-SP has ...stronger potency in inducing inflammatory and genotoxicity response than that of SOAβPin-SP.•SOANap-SP activates Nrf-, AhR-, MMP- and MAPK signaling pathways.
The health effects of exposure to secondary organic aerosols (SOAs) are still limited. Here, we investigated and compared the toxicities of soot particles (SP) coated with β-pinene SOA (SOAβPin-SP) and SP coated with naphthalene SOA (SOANap-SP) in a human bronchial epithelial cell line (BEAS-2B) residing at the air–liquid interface. SOAβPin-SP mostly contained oxygenated aliphatic compounds from β-pinene photooxidation, whereas SOANap-SP contained a significant fraction of oxygenated aromatic products under similar conditions. Following exposure, genome-wide transcriptome responses showed an Nrf2 oxidative stress response, particularly for SOANap-SP. Other signaling pathways, such as redox signaling, inflammatory signaling, and the involvement of matrix metalloproteinase, were identified to have a stronger impact following exposure to SOANap-SP. SOANap-SP also induced a stronger genotoxicity response than that of SOAβPin-SP. This study elucidated the mechanisms that govern SOA toxicity and showed that, compared to SOAs derived from a typical biogenic precursor, SOAs from a typical anthropogenic precursor have higher toxicological potency, which was accompanied with the activation of varied cellular mechanisms, such as aryl hydrocarbon receptor. This can be attributed to the difference in chemical composition; specifically, the aromatic compounds in the naphthalene-derived SOA had higher cytotoxic potential than that of the β-pinene-derived SOA.
In this study we investigated the possible causal role for soluble metal species extracted from roadway traffic emissions in promoting particulate matter (PM)-induced reactive oxygen species (ROS) ...production and antioxidant response element (ARE) promoter activation. To this end, these responses have been evaluated in alveolar macrophage and epithelial lung cells that have been exposed to ‘Unfiltered’, ‘Filtered’ and ‘Filtered+Chelexed’ water extracts of PM samples collected from the roadway urban environments of Thessaloniki, Milan and London. Except for Thessaloniki, our results demonstrate that filtration resulted in a minor decrease in ROS activity of the fine PM fraction, suggesting that ROS activity is attributed mainly to water-soluble PM species. In contrast to ROS, ARE activity was mediated predominantly by the water-soluble component of PM present in both the fine and coarse extracts. Further removal of metals by Chelex treatment from filtered water extracts showed that soluble metal species are the major factors mediating ROS and ARE activities of the soluble fraction, especially in the London PM extracts. Finally, utilizing step-wise multiple-regression analysis, we show that 87% and 78% of the total variance observed in ROS and ARE assays, respectively, is accounted for by changes in soluble metal concentration. Using a statistical analysis we find that As, Zn and Fe best predict the ROS-generating/ARE-activating capacity of the near roadway particulate matter in the pulmonary cells studied. Collectively, our findings imply that soluble metals present in roadside PM are potential drivers of both pro- and anti-oxidative effects of PM in respiratory tract.
•Anti/pro-oxidative effects of soluble metals in near roadway PM samples are demonstrated.•Aerosol soluble metal species (e.g. As, Zn, Fe) play a role in ROS and ARE activity.•Metal concentration in near roadway PM correlates with ROS and ARE activity.•Fine particles are important contributors to near roadway PM metal concentrations.
In 2018, 3.8 million premature deaths were attributed to exposure to biomass burning nanoparticles from wood combustion. The objective of this study was to investigate and compare the toxic effect of ...wood-combustion-related biomass burning nanoparticles from three different combustion stages (i.e., flaming, smoldering, and pyrolysis) on alveolar lung cells, by studying cell proliferation, and structural and behavioral parameters. A549 lung epithelial cells were treated with 31, 62, 125, 250, and 500 µg/mL of water-soluble particulate pollutants from wood burning, and measured by means of real-time cell analysis, cell imaging, and phase imaging microscopy. At low concentrations (31 and 62 µg/mL), all three types of wood burning samples exhibited no toxicity. At 125 µg/mL, they caused decreased cell proliferation compared to the control. Exposure to higher concentrations (250 and 500 µg/mL) killed the cells. Cell physical parameters (area, optical volume, eccentricity, perimeter, and optical thickness) and behavioral parameters (migration, motility, and motility speed) did not change in response to exposure to wood burning materials up to a concentration of 125 µg/mL. Exposure to higher concentrations (250 and 500 µg/mL) changed cell perimeter, optical thickness for smoldering and flaming particles, and led to decreased migration, motility, and motility speed of cells. In conclusion, all three of the combustion water-soluble organic pollutants were identified as equally toxic by real-time cell analysis (RTCA) results. The parameters describing cell structure suggest that pyrolysis particles were slightly less toxic than others.
PDF
