Inhalation Toxicology最新文献

Background: Cigarette smoking stands as a prominent contributor to global mortality rates, and its impact spans both immediate and long-term effects on hematological parameters; however, in addition to controversial results in previous studies, its effect on novel inflammatory indices has yet to be thoroughly investigated. Thus, this study aims to assess the impact of various smoking profiles on total white blood cell (WBC) count, WBC differentials, and novel hematologic-inflammatory indices among males.

Methods: This cross-sectional study was conducted on 4039 male adults from the enrollment phase data of the TABARI cohort population in Iran. WBC, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), absolute monocyte count (AMC), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), platelet-to-HDL ratio (PHR), RDW-to-platelet ratio (RPR), lymphocyte-to-HDL ratio (LHR), monocyte-to-HDL ratio (MHR), and neutrophil-to-HDL ratio (NHR) were compared between smokers and nonsmokers and also within smokers with different smoking intensities (pack/year). Comparisons were made by Chi-square test and one-way ANOVA, and further done using multivariate linear regression after adjustment for confounders.

Results: WBC, ANC, ALC, AMC, LMR, PLR, PHR, LHR, MHR, and NHR were significantly higher in smokers compared to nonsmokers in a dose-dependent manner (p < 0.05). The multivariate linear regression showed that among smokers, WBC was 25.3% higher, ANC and ALC were 19.7% higher, and AMC was 12.2% higher compared to nonsmokers (all p < 0.001).

Conclusion: Our results demonstrated that WBC, ANC, ALC, AMC, PHR, LHR, MHR, and NHR exhibit significant dose-dependent elevations in smokers.

Background: Chemicals released during cigarette smoking disrupt the structure, function and physiological capacity of the cardiovascular system. Detoxification of these harmful chemicals is done by Glutathione S-transferase (GST) isoenzymes (GSTM1 and GSTT1). GST gene polymorphisms may have a role in conferring susceptibility to coronary artery disease. This case-control study aims to evaluate the relationship between GSTM1 and GSTT1 gene polymorphisms, smoking habits, and coronary artery disease (CAD) in the Northern Indian population of Jammu and Kashmir, strengthened by a meta-analysis based on previously published studies.

Methods: The current study involved 220 patients with CAD and 240 healthy controls from the Jammu region in the Union Territory of Jammu and Kashmir. Whole blood DNA was isolated, followed by genotyping using the polymerase chain reaction (PCR) technique.

Results: Smoking, a non-vegetarian diet, and lipid levels were found to be significantly associated with coronary artery disease (CAD). The frequency of the GSTM^null genotype was significantly higher in patients than in controls (48.2% vs. 33.3%), while both groups showed comparable frequencies of the GSTT^null genotype. Combined genotype analysis indicated that the GSTM1 T^null genotype was associated with an increased risk of CAD, with an adjusted odds ratio (AOR) of 1.70 and a 95% confidence interval (CI) of 1.30-2.27(p = 0.05). Patients who were smokers and had the GSTM^null genotype, as well as those with the GSTM1T^null or GSTM^nullT1 genotypes, were at a significantly higher risk of developing CAD. The results of the meta-analysis supported the findings of the case-control association study.

Conclusion: The GSTM1 null genotype, either independently or in conjunction with smoking, is linked to the incidence of CAD among North Indians in Jammu and Kashmir.

Purpose: Dysfunction of pulmonary microvascular endothelial cells (PMVECs) is an important feature of pulmonary embolism (PE) in sepsis. This study aimed to explore the impact of caspase recruitment domain-containing protein 9 (CARD9) on sepsis-induced PE. Materials and Methods: Proteomic analysis was performed on serum of sepsis patients with PE to identify differentially expressed proteins. Wild-type (WT) and CARD9 knockout (KO) mice were used to establish PE in sepsis mouse model. In vitro and in vivo sepsis models were established to evaluate PMVEC function. Tiliroside (TIS) was tested for its therapeutic effects via modulation of the CARD9-mediated MAPK/NF-κB pathway. Results: In the pulmonary vascular endothelial tissues of mice with sepsis, a total of 46 proteins exhibited differential expression, and CARD9 was one of the changes proteins. Both CARD9 knockout (KO) and silencing were found to effectively ameliorate sepsis-induced dysfunction of PMVECs in both in vivo and in vitro models of sepsis. Tiliroside (TIS), an active constituent derived from Buddleja officinalis Maxim, demonstrated a significant capacity to enhance the function of PMVECs in sepsis by modulating the CARD9-mediated MAPK/NF-κB signaling pathway. Conclusion: In summary, CARD9 emerges as a potential molecular target for the treatment of sepsis-associated PE dysfunction.

Occupational exposure to crystalline silica (CS) is known to induce silicosis, a chronic lung disease characterized by the formation of granulomas and severe lung fibrosis. Specifically, individuals exposed to low doses of CS may develop silicosis after a decade or more of exposure. Similarly, in rat silicosis models exposed to occupationally relevant doses of α-quartz, there is an initial phase characterized by minimal and well-controlled pulmonary inflammation, followed by the development of robust and persistent inflammation. During the initial phase, the inflammation provoked by α-quartz is subdued by two mechanisms. Firstly, α-quartz particles are engulfed by alveolar macrophages (AMs) of the alternatively activated (M2) subtype and interstitial macrophages (IMs), limiting their interaction with other lung cells. Secondly, the anti-inflammatory cytokine, interleukin (IL)-10, is constitutively expressed by these macrophages, further dampening the inflammatory response. In the later inflammatory phase, IL-10-dependent anti-inflammatory state is disrupted by Type I interferons (IFNs), leading to the production of pro-inflammatory cytokines in response to α-quartz, aided by lipopolysaccharides (LPS). This review delves into the complex pathways involving IL-10, LPS, and Type I IFNs in α-quartz-induced pulmonary inflammation, offering a detailed analysis of the underlying mechanisms and identifying areas for future research.

Objective: The objectives are to develop inhalation dosimetry models of the flavoring agents diacetyl, 2, 3-pentanedione, and acetoin to predict uptake throughout the rat and human respiratory tracts and use the results with histopathology data from 2-week, nose-only inhalation exposures in Sprague-Dawley rats to assess relationships between predicted dose and in vivo responses.

Methods: Computational fluid dynamics (CFD) models of the nasal passages were used to simulate inspiratory airflow and vapor uptake and mechanistic models of the lung airways were used to simulate vapor uptake during a breathing cycle.

Results: Diacetyl and 2, 3-pentanedione demonstrated similar uptake and wall mass flux patterns throughout the respiratory tract. Acetoin, being more soluble, was rapidly absorbed in the nasal and upper lung airways. At a 10 ppm exposure concentration and resting breathing conditions, nasal uptake of diacetyl, 2, 3-pentanedione, and acetoin was 30.9, 30.3, and 73.6% in the rat, and 8.7, 9.3, and 32.5% in the human, respectively; total respiratory tract uptake was 76.5, 76.8, and 93.0% in the rat and 79.6, 81.1, and 85.9% in the human, respectively. Wall mass flux patterns aligned with previously reported in vivo observations of histopathological effects in the rat respiratory tract following 8.75, 17.5, or 35 ppm diacetyl or 2, 3-pentanedione exposure and can be used to evaluate dose-response behavior.

Conclusions: Dose-response assessment of inhaled vapors demonstrates the utility of dosimetry models for interspecies extrapolation and chemical comparisons and how their use is an important part of risk characterization as non-animal alternatives are more widely considered.

Deterministic models have been developed for the predictions of the deposited dose to the respiratory tract from inhalation of airborne materials. The complexity of the lung geometry, ventilation mechanics, and transport processes have required model assumptions and simplifications. Model validation is an integral part of the development process before models can be applied to specific scenarios of interest. While several validation efforts have been reported in the literature for regional deposition in the respiratory tract, there is a desire to refine the models to enhance the power of predictions to smaller regions such as per lobe and generation of the respiratory tract. This imperative is contingent on the availability of data. Hence, we refined and validated our lung deposition model developed in rodents by adding additional physical mechanisms missing in the original model. Convective mixing of particles impacts both the distribution and deposited dose of inhaled particles. We developed a semi-empirical mixing model for particle exchange in the pulmonary region between the respiratory ducts and alveoli with parameters determined by fitting the model with recent measurements by Lin et al. The refined model was used to predict lobar, regional, and site -specific deposition of inhaled trace metals in the puff of regular and mentholated little cigars. Model refinements yielded increased deposition throughout the lung and matched deposition predictions more closely with measurements. The refined deposition model can be used to study the risk from inhalation of tobacco products as well as environment particles.

Objectives: The adverse effects of fine particulate matter (PM_2.5), including cardiovascular outcomes, are well established. This review and meta-analysis investigates the association between long-term exposure to low concentration PM_2.5 (<12 µg/m³) and CVD mortality in U.S. and Canadian populations.

Methods: We conducted a literature search and completed random effect meta-analyses.

Results: Twenty-four studies were reviewed, with 12 from each of the U.S. and Canada. Fifteen of eighteen studies that reported hazard ratios (HRs) for total CVD mortality reported statistically significant positive associations with low concentration PM_2.5. For cause-specific CVD mortality, more consistent results were shown for ischemic heart disease (IHD) mortality, with all eleven studies reporting statistically significant associations (HR = 1.09 to 2.48). Only three of 12 studies evaluating cerebrovascular mortality reported statistically significant associations (HR = 1.10 to 1.27). Studies that restricted analyses to participants with mean exposures <12 µg/m³ found statistically significant associations between PM_2.5 and at least some of the CVD mortality outcomes of interest. However, the shape of the concentration-response functions varied widely. Only six studies controlled for at least one additional air pollutant, and multi-pollutant models generally showed an attenuated impact of PM_2.5. Despite existing gaps in understanding the association between low concentrations of PM_2.5 and cardiovascular mortality, this review highlights the critical importance of ongoing efforts to improve air quality for public health benefits.

Conclusions: Continued focus on understanding the shape of the concentration-response function for PM_2.5, the impact of co-pollutants on observed effects, and how particle composition may impact effect estimates, is recommended.

Purpose: Pulmonary exposure to emissions from manipulating solid surface composite (SSC) materials has been associated with adverse health effects in humans and laboratory animals. Previous in vitro and in vivo investigations of SSC toxicity have been limited by particle delivery methods that do not fully recapitulate the workplace environment. This study sought to determine the acute SSC-induced pulmonary responses via whole-body inhalation exposure. Materials and Methods: A chamber for dust particle generation and an exposure system for characterization and animal exposures was constructed. The system successfully generated SSC at a concentration of 19.9 ± 1.5 mg/m³. The aerosol count median aerodynamic diameter was 820 nm. First, C57BL/6 mice were exposed to SSC particles for 4 h (n = 6) or filtered air control followed by euthanasia either immediately or 24 h post-exposure. Lungs were analyzed for aluminum (Al) content using inductively coupled plasma atomic emission spectroscopy (ICP-AES) which measured a lung deposition of 19.13 ± 5.03 µg/g elemental Al, or approximately 64 µg/g SSC dust. Second, a group of mice (n = 9) was exposed to SSC particles at 20 mg/m³ for 4 days, 4 h/day to assess the acute and sub-chronic pulmonary effects of SSC inhalation. Animals were euthanized at 1- and 56-days post-exposure. Results: Total estimated pulmonary deposition for these animals was 49.2 µg SSC dust/animal. No histopathologic changes were observed at any post-exposure time point; however, BALF total protein was increased at 1-day post-exposure. Conclusions: We conclude that exposure to dust from cutting SSC at this dose and post-exposure durations induces mild, transient inflammation.

Objective: The present study evaluated urinary oxidative stress (OxS) biomarkers to explain the extrapulmonary effect of renal function decline due to subchronic inhalation exposure to particles smaller than 2.5 μm, as well as the correlation of the biomarkers with the particles' endotoxin content.

Materials and methods: Adult male Sprague-Dawley rats were exposed to subchronic inhalation of particles smaller than 2.5 μm (8 weeks, 4 days/week, 5 h/day). The control group was exposed to filtered air. MiniVol and HiVol samplers were used to estimate the concentration and collected particles, respectively. Biomarkers were assessed in weekly urine samples harvested by the metabolic cage. The OxS biomarkers assessed were methylglyoxal, non-esterified fatty acids, malondialdehyde, advanced oxidative protein products, arginase, myeloperoxidase, glutathione S-transferase, and gamma-glutamyl transferase, all of which were evaluated by colorimetric assays. Creatinine was evaluated by the Jaffe reaction, and cystatin-C (Cys-C) and neutrophil gelatinase-associated lipocalin-2 were quantified using Luminex technology. Endotoxin content was analyzed with the Limulus Amebocyte Lysate Pyrochrome Chromogenic Test Kit.

Results and discussion: Subchronic exposure to PM_2.5 increased OxS biomarkers in urine. Endotoxin content showed a positive correlation with the urinary OxS biomarkers evaluated. Additionally, urinary OxS biomarkers correlated with creatinine and the early kidney damage biomarkers Cys-C and neutrophil gelatinase-associated lipocalin-2, where the strongest and positive correlations were observed with the latter two biomarkers.

Conclusions: Inhalation of environmental airborne particles smaller than 2.5 μm increased urinary OxS biomarkers, correlated with endotoxin content and early kidney damage biomarkers. This finding corroborates the extrapulmonary nephrotoxic effect of inhaled particles.

Purpose: In the past decade, microplastics (MPs) have drawn significant attention as widespread environmental contaminants, with research increasingly highlighting their harmful effects on respiratory health in aquatic and terrestrial organisms. Findings revealed microplastics in human lung tissues, raising concerns about their potential role in damaging lung tissue integrity and contributing to pulmonary fibrosis-a chronic inflammatory condition characterized by scarring of lung epithelial tissues due to accumulated extracellular matrix, triggered by factors such as alcohol, pathogens, genetic mutations, and environmental pollutants.

Objective: In this review, we explore both well-studied and lesser-studied mechanisms and signaling pathways, aiming to shed light on how microplastics might act as mediators that activate distinct, often overlooked signaling cascades.

Materials and methods: This review searched PubMed and Google Scholar using keywords like "plastic," "microplastic," "lung fibrosis," "pulmonary system," "exposure route," and "signaling pathways," combined with "OR" and "AND" in singular and plural forms.

Results: These pathways could not only induce lung damage but also play a significant role in the development of pulmonary fibrosis.

Discussion and conclusions: These signaling pathways could also be targeted to reduce microplastic-induced pulmonary fibrosis, opening new avenues for future treatments.