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The heterogeneity and complexity of solvent-extracted organic matter associated with PM 2.5 (SEOM-PM 2.5 ) is well known; however, there is scarce information on its biological effects in human cells. This work aimed to evaluate the effect of SEOM-PM 2.5 collected in northern Mexico City during the cold-dry season (November 2017) on NL-20 cells, a human bronchial epithelial cell line. The SEOM obtained accounted for 15.5% of the PM 2.5 mass and contained 21 polycyclic aromatic hydrocarbons (PAHs). The cell viability decreased following exposure to SEOM-PM 2.5 , and there were noticeable morphological changes such as increased cell size and the presence of cytoplasmic vesicles in cells treated with 5-40 μg/mL SEOM-PM 2.5 . Exposure to 5 μg/mL SEOM-PM 2.5 led to several alterations compared with the control cells, including the induction of double-stranded DNA breaks based (p < 0.001); nuclear fragmentation and an increased mitotic index (p < 0.05); 53BP1 staining, a marker of DNA repair by non-homologous end-joining (p < 0.001); increased BiP protein expression; and reduced ATF6, IRE1α, and PERK gene expression. Conversely, when exposed to 40 μg/mL SEOM-PM 2.5 , the cells showed an increase in reactive oxygen species formation (p < 0.001), BiP protein expression (p < 0.05), and PERK gene expression (p < 0.05), indicating endoplasmic reticulum stress. Our data suggest concentration-dependent toxicological effects of SEOM-PM 2.5 on NL-20 cells, including genotoxicity, genomic instability, and endoplasmic reticulum stress., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Alterations in dopaminergic transmission are associated with neurological disorders, such as depression, autism, and Parkinson's disease. Exposure of rats to ambient fine (FP) or ultrafine (UFP) particles induces oxidative and inflammatory responses in the striatum, a neuronal nucleus with dense dopaminergic innervation and critically involved in the control of motor activity. Objectives: We used an ex vivo system to evaluate the effect of in vivo inhalation exposure to FP and UFP on motor activity and dopaminergic transmission. Materials and Methods: Male adult Wistar rats were exposed to FP, UFP, or filtered air for 8 weeks (subchronic exposure; 5 h/day, 5 days/week) in a particle concentrator. Motor activity was evaluated using the open-field test. Uptake and release of [ 3 H]-dopamine were assessed in striatal synaptosomes, and dopamine D 2 receptor (D 2 R) affinity for dopamine was evaluated by the displacement of [ 3 H]-spiperone binding to striatal membranes. Results: Exposure to FP or UFP significantly reduced spontaneous motor activity (ambulatory distance: FP -25%, UFP -32%; ambulatory time: FP -24%, UFP -22%; ambulatory episodes: FP -22%, UFP -30%), decreased [ 3 H]-dopamine uptake (FP -18%, UFP -24%), and increased, although not significantly, [ 3 H]-dopamine release (113.3 ± 16.3 and 138.6 ± 17.3%). Neither FP nor UFP exposure affected D 2 R density or affinity for dopamine. Conclusions: These results indicate that exposure to ambient particulate matter reduces locomotion in rats, which could be related to altered striatal dopaminergic transmission: UFP was more potent than FP. Our results contribute to the evidence linking environmental factors to changes in brain function that could turn into neurological and psychiatric disorders.HIGHLIGHTSYoung adult rats were exposed to fine (FP) or ultrafine (UFP) particles for 40 days.Exposure to FP or UFP reduced motor activity.Exposure to FP or UFP reduced dopamine uptake by striatal synaptosomes.Neither D 2 R density or affinity for dopamine was affected by FP or UFP.UFP was more potent than FP to exert the effects reported.

PM 2.5 exposure is associated with a glomerular filtration rate (GFR) reduction, and renal tissue damage. The goal of this study was demonstrate the acute effect of PM 2.5 on the kidney. Male rats were acutely exposed to PM 2.5 or filtered air. Blood pressure was mesure and early kidney biomarkers were evaluated in serum and urine samples, and also IL-1β, IL-6 and TNFα were determined. Oxidative biomarkers, angiotensin/bradykinin-related proteins, KIM-1, IL-6 and histology were determined. Blood pressure, GFR, and early kidney damage biomarkers increase together with oxidative biomarkers and angiotensin/bradykinin endocrine-related proteins increased after exposure to PM 2.5 . Urinary IL-6 increased after exposure to PM 2.5 , whereas in kidney cortex decreased. Histological changes were observed and accompanied by the induction of KIM-1. Acute exposure to PM 2.5 not decline kidney function. However, it can induce early kidney damage biomarkers, oxidative stress, inflammation and angiotensin mediators, which perhabs culminates in a lose of renal function., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The exposure to environmental pollutants, such as fine and ultrafine particles (FP and UFP), has been associated with increased risk for Parkinson's disease, depression and schizophrenia, disorders related to altered dopaminergic transmission. The striatum, a neuronal nucleus with extensive dopaminergic afferents, is a target site for particle toxicity, which results in oxidative stress, inflammation, astrocyte activation and modifications in dopamine content and D 2 receptor (D 2 R) density. In this study we assessed the in vitro effect of the exposure to FP and UFP on dopaminergic transmission, by evaluating [ 3 H]-dopamine uptake and release by rat striatal isolated nerve terminals (synaptosomes), as well as modifications in the affinity and signaling of native and cloned D 2 Rs. FP and UFP collected from the air of Mexico City inhibited [ 3 H]-dopamine uptake and increased depolarization-evoked [ 3 H]-dopamine release in striatal synaptosomes. FP and UFP also enhanced D 2 R affinity for dopamine in membranes from either rat striatum or CHO-K1 cells transfected with the long isoform of the human D 2 R (hD 2L R)2LR). In CHO-K1-hD2L In CHO-K1-hD 2L R cells or striatal slices, FP and UFP increased the potency of dopamine or the D 2 R agonist quinpirole, respectively, to inhibit forskolin-induced cAMP formation. The effects were concentration-dependent, with UFP being more potent than FP. These results indicate that FP and UFP directly affect dopaminergic transmission., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: A rich body of literature exists that has demonstrated adverse human health effects following exposure to ambient air particulate matter (PM), and there is strong support for an important role of ultrafine (nanosized) particles. At present, relatively few human health or epidemiology data exist for engineered nanomaterials (NMs) despite clear parallels in their physicochemical properties and biological actions in in vitro models., Objectives: NMs are available with a range of physicochemical characteristics, which allows a more systematic toxicological analysis. Therefore, the study of ultrafine particles (UFP, <100 nm in diameter) provides an opportunity to identify plausible health effects for NMs, and the study of NMs provides an opportunity to facilitate the understanding of the mechanism of toxicity of UFP., Methods: A workshop of experts systematically analyzed the available information and identified 19 key lessons that can facilitate knowledge exchange between these discipline areas., Discussion: Key lessons range from the availability of specific techniques and standard protocols for physicochemical characterization and toxicology assessment to understanding and defining dose and the molecular mechanisms of toxicity. This review identifies a number of key areas in which additional research prioritization would facilitate both research fields simultaneously., Conclusion: There is now an opportunity to apply knowledge from NM toxicology and use it to better inform PM health risk research and vice versa. https://doi.org/10.1289/EHP424.

Background: Observed seasonal differences in particulate matter (PM) associations with human health may be due to their composition and to toxicity-related seasonal interactions., Objectives: We assessed seasonality in PM composition and in vitro PM pro-inflammatory potential using multiple PM samples., Methods: We collected 90 weekly PM10 and PM2.5 samples during the rainy-warm and dry-cold seasons in five urban areas with different pollution sources. The elements, polycyclic aromatic hydrocarbons (PAHs), and endotoxins identified in the samples were subjected to principal component analysis (PCA). We tested the potential of the PM to induce tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6) secretion in cultured human monocytes (THP-1), and we modeled pro-inflammatory responses using the component scores., Results: PM composition varied by size and by season. PCA identified two main components that varied by season. Combustion-related constituents (e.g., vanadium, benzo[a]pyrene, benzo[a]anthracene) mainly comprised component 1 (C1). Soil-related constituents (e.g., endotoxins, silicon, aluminum) mainly comprised component 2 (C2). PM from the rainy-warm season was high in C2. PM (particularly PM2.5) from the dry-cold season was rich in C1. Elevated levels of cytokine production were associated with PM10 and C2 (rainy-warm season), whereas reduced levels of cytokine production were associated with PM2.5 and C1 (dry-cold season). TNFα secretion was increased following exposure to PM with high (vs. low) C2 content, but TNFα secretion in response to PM was decreased following exposure to samples containing ≥ 0.1% of C1-related PAHs, regardless of C2 content. The results of the IL-6 assays suggested more complex interactions between PM components and particle size., Conclusions: Variations in PM soil and PAH content underlie seasonal and PM size-related patterns in TNFα secretion. These results suggest that the mixture of components in PM explains some seasonal differences in associations between health outcomes and PM in epidemiologic studies., Citation: Manzano-León N, Serrano-Lomelin J, Sánchez BN, Quintana-Belmares R, Vega E, Vázquez-López I, Rojas-Bracho L, López-Villegas MT, Vadillo-Ortega F, De Vizcaya-Ruiz A, Rosas Perez I, O'Neill MS, Osornio-Vargas AR. 2016. TNFα and IL-6 responses to particulate matter in vitro: variation according to PM size, season, and polycyclic aromatic hydrocarbon and soil content. Environ Health Perspect 124:406-412; http://dx.doi.org/10.1289/ehp.1409287.

Particulate matter (PM)-associated metals can contribute to adverse cardiopulmonary effects following exposure to air pollution. The aim of this study was to investigate how variation in the composition and size of ambient PM collected from two distinct regions in Mexico City relates to toxicity differences. Male Wistar Kyoto rats (14 wk) were intratracheally instilled with chemically characterized PM10 and PM2.5 from the north and PM10 from the south of Mexico City (3 mg/kg). Both water-soluble and acid-leachable fractions contained several metals, with levels generally higher in PM10 South. The insoluble and total, but not soluble, fractions of all PM induced pulmonary damage that was indicated by significant increases in neutrophilic inflammation, and several lung injury biomarkers including total protein, albumin, lactate dehydrogenase activity, and γ-glutamyl transferase activity 24 and 72 h postexposure. PM10 North and PM2.5 North also significantly decreased levels of the antioxidant ascorbic acid. Elevation in lung mRNA biomarkers of inflammation (tumor necrosis factor [TNF]-α and macrophage inflammatory protein [MIP]-2), oxidative stress (heme oxygenase [HO]-1, lectin-like oxidized low-density lipoprotein receptor [LOX]-1, and inducibile nitric oxide synthase [iNOS]), and thrombosis (tissue factor [TF] and plasminogen activator inhibitor [PAI]-1), as well as reduced levels of fibrinolytic protein tissue plasminogen activator (tPA), further indicated pulmonary injury following PM exposure. These responses were more pronounced with PM10 South (PM10 South > PM10 North > PM2.5 North), which contained higher levels of redox-active transition metals that may have contributed to specific differences in selected lung gene markers. These findings provide evidence that surface chemistry of the PM core and not the water-soluble fraction played an important role in regulating in vivo pulmonary toxicity responses to Mexico City PM.

Spatial variation in particulate matter-related health and toxicological outcomes is partly due to its composition. We studied spatial variability in particle composition and induced cellular responses in Mexico City to complement an ongoing epidemiologic study. We measured elements, endotoxins, and polycyclic aromatic hydrocarbons in two particle size fractions collected in five sites. We compared the in vitro proinflammatory response of J774A.1 and THP-1 cells after exposure to particles, measuring subsequent TNFα and IL-6 secretion. Particle composition varied by site and size. Particle constituents were subjected to principal component analysis, identifying three components: C(1) (Si, Sr, Mg, Ca, Al, Fe, Mn, endotoxin), C(2) (polycyclic aromatic hydrocarbons), and C(3) (Zn, S, Sb, Ni, Cu, Pb). Induced TNFα levels were higher and more heterogeneous than IL-6 levels. Cytokines produced by both cell lines only correlated with C(1) , suggesting that constituents associated with soil induced the inflammatory response and explain observed spatial differences., (© 2013 Wiley Periodicals, Inc.)

We have previously reported that airborne particulate matter air pollution (PM) activates the intrinsic apoptotic pathway in alveolar epithelial cells through a pathway that requires the mitochondrial generation of reactive oxygen species (ROS) and the activation of p53. We sought to examine the source of mitochondrial oxidant production and the molecular links between ROS generation and the activation of p53 in response to PM exposure. Using a mitochondrially targeted ratiometric sensor (Ro-GFP) in cells lacking mitochondrial DNA (rho0 cells) and cells stably expressing a small hairpin RNA directed against the Rieske iron-sulfur protein, we show that site III of the mitochondrial electron transport chain is primarily responsible for fine PM (PM2.5)-induced oxidant production. In alveolar epithelial cells, the overexpression of SOD1 prevented the PM2.5-induced ROS generation from the mitochondria and prevented cell death. Infection of mice with an adenovirus encoding SOD1 prevented the PM2.5-induced death of alveolar epithelial cells and the associated increase in alveolar-capillary permeability. Treatment with PM2.5 resulted in the ROS-mediated activation of the oxidant-sensitive kinase ASK1 and its downstream kinase JNK. Murine embryonic fibroblasts from ASK1 knock-out mice, alveolar epithelial cells transfected with dominant negative constructs against ASK1, and pharmacologic inhibition of JNK with SP600125 (25 microM) prevented the PM2.5-induced phosphorylation of p53 and cell death. We conclude that particulate matter air pollution induces the generation of ROS primarily from site III of the mitochondrial electron transport chain and that these ROS activate the intrinsic apoptotic pathway through ASK1, JNK, and p53.

Exposure to high levels of particulate matter <2.5 µm (PM2.5) causes cardiorespiratory diseases due to oxidative stress and inflammation. The toxicity of PM2.5 depends on particle size and composition. PM2.5 can reach organs far from the lungs, such as the brain, heart, kidneys, and adipose tissue, affecting their function. Moreover, endotoxin, an important component of PM2.5, has recently been suggested as a risk factor for the development of metabolic, autoimmune, neurodegenerative, and renal diseases. Most published studies focus only on cardiorespiratory symptoms, airway inflammation, and impaired lung function. An amplified inflammation of the airways can transcend to other organs and cause genetic, biochemical, tissue, and physiological alterations. This review focuses on the role of endotoxin as an air pollutant, its adverse health effects, and the discussion on whether it should be considered as an air quality parameter. [ABSTRACT FROM AUTHOR]