Particle and Fibre Toxicology最新文献

Background: Exposure to air pollution including contemporary sources like wildland fire smoke worsens cardiovascular outcomes. Although several mechanisms for these effects have been postulated, one underexplored impact of inhaled air pollution that may mediate adverse health outcomes is sleep disruption, which is an independent risk factor for cardiovascular morbidity and a trigger of multiple biological pathways linked to disease. The purpose of this study was to determine whether cardiovascular responses to air pollution, especially excursions in blood pressure, are associated with contemporaneous changes in sleep status. Three-month old male and female Sprague Dawley rats were implanted with radiotelemetry devices that simultaneously measured aortic blood pressure and the electroencephalogram (EEG), which was used to quantify sleep quality and depth. Heart rate variability (HRV), an indirect measure of autonomic tone, and blood pressure variability (BPV) were assessed from the blood pressure signal. Rats were monitored before, during and after a single 1-hour whole body inhalation exposure to filtered air or tube furnace-generated eucalyptus smoke (632-904 µg/m³ fine particulate matter (PM_2.5; ≤ 2.5 microns in aerodynamic diameter)), a key wildland fire-linked air pollution source.

Results: Smoke exposure caused increases in heart rate, blood pressure, BPV, and HRV markers of sympathetic tone and concomitant disruption in several sleep parameters including slow-wave and paradoxical sleep, and wake duration to varying degrees in male and female rats relative to sex-matched filtered air controls during exposure.After exposure, smoke caused decreases in cardiovascular function and sympathetic tone that again varied by sex, although both males and females had rebound increases in sleep drive. Finally, although there were some minor sex differences, the cardiovascular and sleep responses in the smoke groups were largely more strongly correlated with one another and with HRV markers of sympathetic tone relative to responses in the respective filtered air groups.

Conclusions: These findings suggest that some of the cardiovascular responses to air pollution, including hypertension, may be related to perturbations in sleep and associated changes in autonomic tone.

Background: Tin mine dust (MD), a by-product of tin mining and rock drilling, is a significant contributor to miners' pneumoconiosis. This aerosolized dust is a complex mixture of mineral components, including potentially toxic heavy metals such as arsenic, which may contribute to the development of pneumoconiosis and lung cancer. This study investigates the inhalation toxicity of tin MD samples on pulmonary cells using an Air-Liquid Interface (ALI) exposure model.

Results: MD-A was characterized by high arsenic content, exceeding 30%. In contrast, the elemental composition of MD-B and MD-C was predominantly composed of calcium, magnesium, and aluminum. In the toxicity study, key toxicological endpoints (cell viability, cytotoxicity, pro-inflammatory markers, and cell barrier function) were systematically assessed, and real-time monitoring of the cell-delivered MD particles (MD-A, MD-B, MD-C, and silica) concentrations was achieved using QCM. MD-A significantly enhanced the proliferation ability of 16HBE and Calu-3 cells compared to other particulate matters, indicating arsenic-containing MD promotes cell proliferation. MD-A resulted in an increase in IL-1β mRNA expression in 16HBE cells; elevations in IL-1β, IL-6, IL-8, TNF-α, and CCL2 mRNA were observed in Calu-3 cells. Additionally, treatment with four different particles significantly increased the mRNA expression of MUC5AC in both cell types. Immunofluorescence staining demonstrated alterations in the typical morphology of epithelial cells exposed to arsenic-containing MD and silica particles. In this study, it was shown that four types of particles delivered via suspension to the same in vitro model can induce differing levels of cytotoxicity and proinflammatory responses. The differences in results underscore the specific effects of the inherent physicochemical attributes of particles on biological interactions.

Conclusions: Under identical particle size conditions, in vitro studies on inhalation toxicity reveal that the chemical composition of particulate matter causes varying degrees of toxic damage to cells. This study utilizes an advanced in vitro method to assess the inhalation hazards of tin MD particles by integrating the ALICE system. The chemical complexity of tin MD, particularly its significant arsenic content, requires special attention and thorough evaluation.

Background: Inhaled nanomaterials can translocate from the lungs into systemic circulation and reach the liver, which is the main secondary organ for nanomaterial uptake, potentially causing adverse effects. Understanding how inhaled nanomaterials localize within liver tissue is important for understanding their clearance mechanisms and potential toxicity. Previous in vivo studies have primarily focused on spherical particles, highlighting the need for studies on fiber-shaped nanomaterials.

Methods: This study examines the hepatic distribution of five fiber-shaped nanomaterials (three multiwalled carbon nanotubes, gallium phosphide nanowires, and short TiO₂ nanotubes) compared to spherical TiO₂ nanoparticles. Liver samples were collected at 1, 3, 6, and 12 months after pulmonary exposure using a single intratracheal (IT) instillation in mice. Paraffin-embedded liver sections were stained with Hematoxylin and Eosin (H&E), and analyzed using enhanced darkfield microscopy. The localization of the nanomaterials within sections was categorized into four categories: hepatocyte, non-parenchymal cell, sinusoid/vessel, and another placement. Localization was further validated using cell-specific immunohistochemical staining. Furthermore, morphological changes were assessed in liver sections and 1 year post-exposure from mice following pulmonary exposure to eleven different MWCNTs.

Results: The hepatic localization of six different nanomaterials were assessed, with more than 10,000 fibers or particles manually counted across all samples. There were significant differences in the localization of long and thick fibers as compared to spherical nanoparticles and short and thin fibers, at all assessed post-exposure time points. Long and thick fiber-shaped nanomaterials were more frequently localized within the liver parenchyma compared to spherical particles and the short TiO₂ tubes, which were more frequently found in non-parenchymal cells. Histological analysis revealed that short, thin, and entangled MWCNTs caused minor tissue alterations, including inflammatory cell infiltration and mild connective tissue hyperplasia in portal zones, whereas long and thick MWCNTs did not induce morphological changes.

Conclusion: These findings demonstrate that the intrahepatic localization of nanomaterials is strongly influenced by fiber shape and dimensions.

Background: Our previous work showed that exposure to multi-walled carbon nanotubes (MWCNTs) exacerbates allergic lung disease in mice induced by house dust mite extract (HDME). Furthermore, mice genetically deficient in the proteinase-activated receptor 2 (PAR2) exhibited reduced airway fibrosis after co-exposure to MWCNTs and HDME. The objective of this study was to determine whether inhibition of PAR2 signaling, using the monoclonal antibody SAM-11, attenuates MWCNT exacerbation of HDME-induced allergic lung disease.

Methods: C57BL/6J mice were exposed to MWCNTs in the presence or absence of HDME via oropharyngeal aspiration over a 21-day protocol. SAM-11 or isotype control antibodies were administered prior to exposure. Bronchoalveolar lavage fluid (BALF) and lung tissue were analyzed for markers of allergic inflammation, airway remodeling, and fibrosis.

Results: SAM-11 treatment significantly reduced airway collagen deposition, eosinophilic inflammation, mucous cell metaplasia, and CD3⁺ T cell lung infiltration induced by co-exposure to MWCNTs and HDME. SAM-11 treatment also reduced lung mRNA expression of mediators involved in allergic lung disease (Col1a, Tgf-b1, Arg-1, Il-33, Muc5b), as well as STAT6 and Arg-1 protein in lung tissue.

Conclusion: Inhibition of canonical PAR2 signaling using SAM-11 attenuates multiple features of MWCNT-enhanced allergic lung disease with broader efficacy than PAR2-deficient models. These findings highlight PAR2 as a viable therapeutic target in allergic lung disease and asthma, suggesting that antibody-based blockade is a promising strategy for mitigating allergen and particle-induced disease.

Rationale and objective: Inhaled black carbon (BC) has been previously shown to reach and accumulate in the kidneys. As kidneys filter toxicants, they may be susceptible to adverse effects caused by BC accumulation. We studied gene expressions and pathways related to BC particle load in kidney biopsy tissue.

Study design: Gene expression was measured in 29 kidney biopsies performed at one or two years post-transplantation using Affymetrix microarray. We performed a transcriptome-wide association analysis using linear regression analyses, adjusting for individual characteristics to investigate alterations in gene expression in association with kidney BC. Finally, we performed overrepresentation analyses (ConsensusPathDB) to identify enriched pathways and gene ontology sets.

Results: The geometric mean (5th, 95th percentile) of BC particle levels was 5.4 × 10³ (1.5 × 10³, 4.1 × 10⁴) number of BC particles per mm³ kidney tissue. The BC particle load associated with gene expression in overrepresenting pathways related to ciliopathies, macrophage-derived proteins involved in anti-inflammatory response, DNA damage response, TP53 regulation, and necrosis. We identified BC associated genes involved in GO terms ciliogenesis and ciliary structure, including genes involved in the ciliary plasm and axoneme. Furthermore, we found significantly BC-associated genes involved in RNA-related processes, including e.g., genes in the integrator complex.

Conclusions: Here, we identified genes and pathways associated with real-life kidney BC particle load, indicating alterations in gene expression involved in assembly and maintenance of primary cilia, the anti-inflammatory properties of the innate immune system, and DNA damage-related pathways. These findings highlight the need for public health measures to reduce exposure and protect kidney health in at-risk populations.

Background: Micro/nanoplastics (MNPs) are a commonly detected environmental contaminant in indoor and outdoor environments. Airborne MNPs are of various shapes and sizes, some of which are small enough to reach the deep lung if inhaled. Current research into the toxicity of airborne MNPs in the lung has only involved a small number of polymers and shapes due to their limited availability. The most commonly available are polystyrene spheres and to date, these have been used in the majority of studies, though their relevance to environmental MNPs is limited. To address this gap, we aimed to develop a method to fabricate MNPs of three environmentally relevant polymers, producing both micro- and nano-sized particles as well as fibres. Enhancing the consistency and accessibility of test materials will enable researchers to better investigate how size, shape, and polymer type influence lung toxicity, while also reducing variability introduced during fabrication.

Results: We successfully developed methods to fabricate MNPs of polyamide, polystyrene, and polyethylene terephthalate, as microplastics, nanoplastics, and fibres. MNPs were characterized for their chemical purity and size. The size of the fabricated MNPs were found to be of a respirable dimension. As a solvent-based method of preparation was used, leachates from the MNPs were analysed to check for contamination that could cause non-specific toxicity. These were found to have no effect on the metabolic activity of either THP-1 macrophages or transformed type-1 (TT1) epithelial cells.

Conclusions: This work provides pulmonary toxicologists with a method for the fabrication of MNPs and their physical and chemical characteristics. Their characteristics indicate they are a representative test material for experimental systems.

Background: The escalating accumulation of micro- and nanoplastics (MNPs) in the environment has raised significant concerns regarding their neurotoxic potential in vertebrates. This critical review synthesizes evidence from 234 original research articles across aquatic and terrestrial models, as well as in vitro systems, to evaluate the impacts of MNPs on the brain.

Main body: Emerging data suggest that MNPs may reach the brain via olfactory translocation or by penetrating the blood-brain barrier, potentially facilitated by biomolecular corona formation. However, distribution kinetics, long-term retention, and true internal exposure levels remain unresolved. We highlight that neurotoxic outcomes, such as oxidative stress, cholinergic dysfunction, neurotransmitter imbalances, and neuronal apoptosis, vary widely depending on particle size, shape, polymer type, exposure concentration, and host species. Nevertheless, inconsistencies across models and experimental conditions, such as mismatches between oxidative stress markers and behavioral effects or lack of dose-response relationships, hinder mechanistic clarity and translational relevance to human health. Notably, most current studies employ spherical polystyrene particles at supraphysiological concentrations, limiting ecological and clinical extrapolation. Interactions with microbial biofilms and host microbiota are largely unexplored, despite their probable role in modulating neurotoxicity via the gut-brain axis. Moreover, most studies rely on analytical methods validated only for microplastic detection, while robust, standardized approaches for identifying nanoplastics in environmental and biological matrices remain lacking. These gaps hinder accurate exposure quantification, obscure tissue-specific accumulation patterns, and complicate human health risk estimation.

Conclusion: To advance the field, we recommend comprehensive physicochemical characterization of MNPs, adoption of environmentally relevant exposure scenarios, inclusion of diverse polymer types and shapes, and mechanistic integration through multi-omics and adverse outcome pathway frameworks. Addressing these challenges through harmonized methodologies and interdisciplinary collaboration is essential for developing predictive models of MNP-induced neurotoxicity and informing human health risk assessments.

Background: Air pollution, specifically fine particulate matter (PM_2.5), in China is responsible for millions of excess deaths each decade. Examinations of Chinese municipalities have revealed correlations between ambient PM_2.5 levels and the prevalence and severity of respiratory viral infections. Seasonal sources of ambient PM_2.5 vary, with coal combustion for indoor heating significantly contributing during colder months. Due to this seasonality, we hypothesized that PM_2.5 collected in Xinxiang, China would differentially alter the response to subsequent influenza A/California/04/2009 (H1N1) viral infection in a primary human nasal epithelial cell (HNEC) culture model in a seasonality-specific manner. After the PM_2.5 samples were chemically analyzed, HNECs collected from males (N = 4) and females (N = 3) grown at air-liquid interface were exposed to 22 µg/cm² of seasonal PM_2.5 followed by inoculation with influenza A H1N1 at MOI = 0.001. At 2 and 24 h post infection (p.i.) we assessed transcriptional changes and basolateral release of immune and antiviral mediators.

Results: Summer and fall PM_2.5 samples contained a greater organic carbon mass fraction compared to winter and spring. Winter contained the largest mass fraction of anionic components and spring the largest inorganic element mass fraction. Exposure to the seasonal PM_2.5 samples without infection induced a moderate transcriptional response at 2 h, with the winter PM_2.5 inducing the greatest response. The seasonal PM_2.5 exposures followed by viral infection resulted in a more robust transcriptional response at 2 h p.i. with the winter, spring, and fall PM_2.5 samples (but not the summer PM_2.5) upregulating many inflammatory pathways. At 24 h p.i., only the spring PM_2.5 sample increased inflammatory and antiviral mediator proteins in the basolateral medium, while winter PM_2.5 increased these inflammatory markers in the mock infected cultures.

Conclusions: Seasonal variations in PM2.5 composition during winter, spring, and fall-coinciding with influenza season-likely enhance pro-inflammatory responses to viral infection, with early inflammation contributing to worsened pathogenesis.

Background: Nanoplastics (NPs) are emerging contaminants posing significant risks to human health due to their enhanced cellular penetration. NPs have been shown to damage human testes and epididymides, impairing male fertility. However, the specific testicular damage and underlying mechanisms induced by NPs at different ages have not been thoroughly investigated.

Results: In this study, we exposed young (3-month-old) and old (17-month-old) male mice to long-term (3 months) polystyrene nanoplastics (PS-NPs). The results showed that PS-NPs extensively disrupted testicular structures and functions in both age groups, leading to excessive germ cell loss, tubular degeneration, fibrosis, and declined sperm quality. Young mice exhibited premature testicular aging, while old mice showed more severe testicular damage, indicating age-dependent injury. Mechanistically, proteomics combined with Gene Ontology analysis revealed that PS-NPs primarily disturbed RNA metabolism in young mice, whereas DNA catabolism, collagen, and extracellular matrix metabolism were extensively impaired in old mice. Additionally, integrated proteomic and metabolomic analyses, along with assays conducted on primary Leydig cells, suggested that PS-NPs downregulated scavenger receptor class B type I (SR-BI), consequently impeding testosterone synthesis and aggravating testicular aging in young mice.

Conclusions: Integrated with multi-omics analyses, our study collectively extends the current understanding of PS-NP-induced testicular and sperm toxicology, highlighting age- and duration-dependent risks to male reproduction. Protecting mRNA metabolism and testosterone production may help preserve reproductive capacity in young males exposed to NPs.

Background: Ambient air pollution is a major risk factor for CVDs, and a plausible mechanism is speculated to be alteration of autonomic nervous system (ANS) function. Yet, the short-term effects of air pollution on heart rate variability (HRV), a measure of ANS balance are inconsistent.

Objective: This study aimed to evaluate the short-term effects of ambient PM_2.5 and NO₂ on cardiovascular autonomic function, and to determine vulnerable subgroups and temporal trends from repeated HRV and HR measurements over 14 years in the KORA cohort.

Methods: We analyzed data from 4,032 participants in KORA S4 (1999-2001) and 1,912 in KORA FF4 (2013-2014). Air pollution data were from fixed monitoring stations, and HRV indices were derived from 5-minute ECG recordings. Generalized additive models (GAMs) and generalized additive mixed models (GAMMs) were used to assess associations.

Results: In S4, each IQR increase in PM_2.5 at the 14-day moving average was associated with a 2.32% (95% CI: - 4.41, - 0.19) decrease in SDNN and a 1.20% (95% CI: 0.16, 2.26) increase in HR. By contrast, KORA FF4 showed opposite associations, with a 0.86% (95% CI: 0.02, 1.70) increase in SDNN at lag 4 for PM_2.5. Effect modifications by age and smoking status were observed in S4. No statistically significant associations were found in the longitudinal analysis, however, the observed trends were consistent with the effects identified in S4.

Conclusion: Short-term exposure to PM_2.5 and NO₂ impacts cardiac autonomic function, with varying effects across study waves due to aging, smoking, medication, and lower pollution levels. Even at low ambient concentrations, these exposures impaired autonomic function via inflammation and oxidative stress, underscoring the importance of stringent air quality standards and lifestyle interventions in reducing cardiovascular risk.