Particle and Fibre Toxicology最新文献

A growing body of epidemiological evidence links maternal exposure to air pollution with an increased risk of adverse pregnancy outcomes, such as preterm birth and low birth weight. Cerium dioxide nanoparticles (CeO₂ NPs or nanoceria) are emerging pollutants, used as additives in diesel fuels and cigarettes for their catalytic properties, and released into the environment. Due to their high surface-to-volume ratio and reactivity, CeO₂ NPs develop a surface coating during combustion, which may incorporate other released fuel-borne chemicals, such as benzo[a]pyrene (BaP), a known carcinogen, mutagen and reprotoxicant, raising concerns about their combined impacts on human health. To better reflect environmental reality, we produced BaP-coated CeO₂ NPs and exposed primary human trophoblasts and chorionic villi. Our findings show that BaP-coated CeO₂ NPs activate the aryl hydrocarbon receptor (AhR) pathway, enhancing trophoblast differentiation and syncytium formation, with effects distinct from those of BaP or CeO₂ NPs alone, or their unbound mixture. Additionally, exposure to CeO₂ NPs alone altered homeostasis of mitochondria, affecting their phenotype and function. While individual exposures or BaP-coated CeO₂ NPs had no detectable impact, parallel co-exposure resulted in a slight but significant reduction in basal respiration. Finally, uncoated CeO₂ NPs altered placental steroidogenesis, increasing estrone level while decreasing dehydroepiandrosterone level, with sex-specific effects. These findings suggest that CeO₂ NPs can influence the biological effects of BaP in the human placenta, including modulating trophoblast differentiation, as well as disrupting mitochondria homeostasis and steroid production, with potential implications for pregnancy outcomes in polluted environments.

Background: Wildland fires in the United States have increased in frequency and scale over the past 30 years exposing millions of people to hazardous air pollutants. Among others, aging individuals are particularly vulnerable to the effects of wildfire smoke. In this study, we assessed the neurobiological impacts of wood smoke (WS) on aged mice and the potential of anti-aging therapeutics to mitigate these impacts.

Methods: Female C57BL/6 J mice, aged 18 months, were divided into 10 groups and exposed to either filtered air (FA; 5 groups) or biomass derived WS (5 groups) for 4 h/day, every other day, for 14 days (7 exposures total) with an average particulate matter (PM) concentration of 448 µg/m³ per exposure. One FA control group and one WS exposed group were euthanized 24 h after the last exposure. The remaining 8 groups (4 FA and 4 WS exposed) were treated with either vehicle control, resveratrol and nicotinamide mononucleotide (RNMN), dasatinib and quercetin (DQ), or both RNMN and DQ (RNDQ) for 10 weeks.

Results: A significant reduction in NAD + within the prefrontal cortex was observed following the 14-day exposure to WS along with a reduction in serotonin. Serotonin reductions were observed up to 10 weeks post-exposure and co-occurred with neuroinflammation and behavioral alterations, including increased immobility in a forced swim test. RNMN conferred the greatest mitigating effect after WS exposure, while RNDQ treatment resulted in an upregulation of markers associated with aging in the brain. While the metabolic shift in the PFC following WS exposure was relatively modest, mice exposed to FA and vehicle control (10 weeks of natural aging) exhibited the greatest metabolic shift, including perturbed nicotinamide metabolism.

Conclusion: Taken together, these findings highlight that subacute (14-day) exposure to WS results in persistent neurometabolomic and behavioral alterations in an aged mouse model and that intervention with RNMN may be a useful strategy to mitigate the adverse neurological outcomes observed. Further studies are needed to assess the specific impact of either resveratrol or NMN in isolation and to fully elucidate age-specific, as well as sex- and species-determinant, WS exposure response pathways.

Background: Burn pits, a method for disposal of military waste outside the United States, produce toxic substances, to which 3.5 million military personnel have been and continue to be exposed. Mild asthma (persistent or intermittent symptoms of asthma but no change in pulmonary function tests) is found among military personnel. We investigated whether burn pit combustion products (CPs) are more detrimental to the airways of asthmatic than non-asthmatic mice.

Methods: Mice were exposed to house dust mite antigen (HDM) or phosphate-buffered saline (PBS) 5 times over 2 weeks to initiate asthma-like airway injury. Condensates of CPs or saline were generated by flaming combustion of military cardboard, plastic and military plywood. CPs were aspirated oropharyngeally at 24 h after the final HDM or PBS instillation. The lungs were studied 24 h later.

Results: HDM increased recruitment of eosinophils and mucus projection, both Muc5ac and Muc5b mRNAs and protein. Following exposure to CPs, mice exposed to HDM had a greater inflammatory response and injury, as measured by increased neutrophil recruitment and the concentration of protein in the bronchoalveolar lavage (BAL), than control mice exposed to PBS. Expression of neutrophil chemokines was enhanced. CPs had no effect on HDM-induced eosinophil recruitment or expression of Th2 cytokines. CPs had no effect on mucus production in PBS or HDM mice. However, CPs increased intraluminal mucus, as revealed by AB-PAS staining, only in HDM mice, suggesting that CPs impaired mucociliary clearance (MCC), the lung's primary defense system, only in asthmatic airways. Lung RNA sequencing revealed that CPs increased genes and gene pathways describing inflammatory processes and impaired structure and function of cilia to a greater degree in HDM mice.

Conclusions: These data indicate that asthmatic mice are more susceptible to CP-induced lung remodeling and dysfunction than non-asthmatic mice. Enhanced chemokine expression suggests that the CXCL1,2,5/CXCR2 axis may be the mechanism of the increased neutrophil recruitment. A potential mechanism of mucus accumulation is that inhalation of CPs amplifies the changes in cilia and MCC caused by asthma and triggers a positive feedback loop of enhanced inflammation induced by this accumulating mucus.

Exposure to air pollution has been increasingly recognized as a risk factor for neurodevelopmental disorders, and gut microbiome may play a critical role. However, current evidence still remains scarce. In the present study, mice were exposed to real-time ambient air pollution from conception through young adulthood, with neurobehavioral performance and gut microbiome being assessed across different developmental stages. Neurodevelopmental changes including emotional and cognitive impairments were observed in behavioral tests, accompanied by pathological and inflammation changes in brain, which were more pronounced in adolescence than in young adulthood. Alterations in the compositions and functions of gut microbiome were also revealed by fecal metagenomic sequencing. Mediation analysis showed that gut microbiome alterations significantly contributed to the observed neurodevelopmental changes induced by air pollution. Furthermore, after antibiotic (ABX) intervention, the observed neurobehavioral, pathological and inflammatory differences between the exposed and control groups diminished. These findings indicate that the gut microbiome mediates the neurodevelopmental damage caused by exposure to air pollution during developmental stages, adding novel insights on the underlying mechanisms linking air pollution and neurodevelopmental disorders.

The field of fibre toxicology highlights a significant connection between the physicochemical properties of fibres-such as diameter, length, and durability-and their toxicity when inhaled. Among these properties, durability, particularly in terms of biopersistence and retention time in the lungs, is crucial in determining chronic toxicity. This understanding of fibre biopersistence is especially relevant to the regulation and safety assessment of Man-Made Vitreous Fibres (MMVF), also referred to in North American literature as Synthetic Vitreous Fibres (SVF). Despite its importance, current practices rely heavily on in vivo testing methods for evaluating biopersistence, which conflicts with the movement towards reducing animal testing and utilising new approach methodologies (NAMs) for hazard and risk assessment. In vitro assessments of biodurability have long been employed by the research community and industry alike to investigate the persistence of fibres in the lung, offering an alternative to reduce animal testing to evaluate this critical mediator of fibre toxicity. Here, we explore recent developments in acellular in vitro biodurability approaches for assessing fibre durability in the lung, addressing the variations and key challenges associated with using these methods to determine the safety of bio-soluble MMVF.

Background: Subway systems reduce traffic congestion, air pollution, and carbon dioxide emissions in cities but the impacts of subway air pollution on the health of subway users remain obscure. We conducted a randomized controlled trial involving 83 healthy adults, with 80 included in the final analysis, randomly grouped to spend 2 h daily for 5 consecutive days either in an office or on a subway platform. The fine (PM_2.5) and thoracic (PM₁₀) particles concentrations, temperature, and humidity were monitored. Measurements of health parameters were assessed, including lung function and levels of fractional exhaled nitric oxide (FeNO), inflammatory and oxidative stress biomarkers, and metabolites in serum.

Results: The subway platform exhibited significantly high pollutant levels, with mean PM_2.5 and PM₁₀ concentrations of 193.4 ± 39.4 µg/m³ and 311.5 ± 64.3 µg/m³ respectively. After the 5-day subway exposure, significant declines were observed in lung-function index values, including forced expiratory volume in the first second (FEV1)/forced vital capacity (FVC), maximal voluntary ventilation (MVV) and peak expiratory flow rate (PEFR) as well as serum levels of glutathione peroxidase (GPX)-1 (p < 0.05). Conversely, somatosensory symptom scores, FeNO levels, and serum levels of tumor necrosis factor (TNF)-α and interleukin (IL)-8 were strongly elevated (p < 0.05). Results indicated increased arsenic and cobalt and decreased selenium in urine after the subway exposure (p < 0.05). Finally, the subway exposure was associated with disruptions in seven metabolic pathways and nine metabolites, particularly the depletion of L-cysteine, pretyrosine and O-acetyl-L-serine.

Conclusions: This study provides the first evidence that repeated exposure to subway airborne particles is associated with reduced lung function and increased respiratory and systemic inflammation in healthy adults. Our results underscore the need to develop strategies to mitigate exposure risks, ultimately protecting public health in urban environments.

The rise of microplastic (MPs) pollution presents a pressing environmental issue, raising concerns about its potential health impacts on human populations. Given the critical role of the liver in detoxification and metabolism, understanding the effects of MPs on the human hepatoma cell line HepG2 cells is essential for comprehensively assessing the dangers associated with MPs pollution to human health. Until now, the assessment of the harmful impact of polyethylene (PE) and polyethylene terephthalate (PET) on HepG2 has been incomplete and lacks certain essential data points. In this particular setting, we examined parameters such as cell viability, oxidative stress, mtDNA integrity, mitochondrial membrane potential, and autophagy in HepG2 cells exposed for 72 h to PET and PE at a concentration of 10 µg/mL. Our data revealed that exposure of HepG2 to MPs causes an increase in cell viability accompanied by a heightened ROS and altered mitochondrial function, as revealed by decreased mtDNA integrity and membrane potential. In addition, results demonstrated that exposure to PET and PE activated autophagic events, as suggested by the increased levels of the specific markers LC3 and p62. This last point was further confirmed using bafilomycin, a specific blocker that hinders the merging of autophagosomes and lysosomes, thereby blocking autophagic degradation processes. Given the increasing evidence of food chain MPs contamination and its possible harmful effects, our data should be carefully considered.

Background: While studies demonstrating the adverse effects of air pollution on human health are accumulating, studies on secondary organic aerosol (SOA) are scarce. However, SOA accounts for a significant portion of airborne particulate matter. In particular, pinene biogenic SOA contributes predominantly to SOA loading in the outdoor atmosphere of natural and urban areas and are also emitted indoors because of the presence of terpenes in numerous consumer products. Our aim was to study the immune consequences of acute exposure to β-pinene ozonolysis gaseous and SOA products in mice. This reaction was generated in an atmospheric simulation chamber, and the mice were exposed to the particulate and gaseous products, to the gaseous products only, or to synthetic air 2 h per day for 3 days in real time in a whole-body inhalation chamber. Exposures were performed in adulthood or in utero. Since some adverse effects only occur in individuals weakened by existing immune activation, such as low-grade inflammation, the immune response was measured in the steady state or in a state of moderate systemic inflammation induced by lipopolysaccharide administration.

Results: Exposure of healthy adult mice caused minor immunosuppression in the lungs. However, in adult mice weakened by moderate systemic inflammation, the same exposure conditions revealed that mice exposed to the β-pinene ozonolysis particulate and gaseous products presented deficient pulmonary and systemic immune responses, including excessive recruitment of B lymphocytes, CD4⁺ T lymphocytes, CD11b⁺ dendritic cells, inflammatory monocytes and neutrophils in the lungs and defective recruitment of regulatory T cells in the spleen. In offspring exposed to β-pinene ozonolysis products in utero, the LPS-induced upregulation of Ccl2, Cxcl10 and Icam1 mRNA levels in the lungs and the activation of dendritic cells in the spleen were excessive in female mice. The male offspring developed a normal response to moderate systemic inflammation, except for impaired activation of CD4⁺ T cells and increased activation of CD103⁺ dendritic cells in the spleen.

Conclusion: In mice, pulmonary and systemic immune reactions in response to moderate systemic inflammation are dysregulated by exposure to common secondary oxidation products, highlighting interest in the role of these neglected atmospheric compounds in immune disease development and susceptibility to infections.