Inhalation Toxicology最新文献

Objective(s): Pulmonary fibrosis (PF) is a seriousand advancing respiratory condition that arises from various contributing factors. Bleomycin (BLM) is a chemotherapeutic drug known to cause different side effects, including PF. The current study aimed to assess the protective effects of the Tannic Acid/Iron complex (TAIC) against PF induced by BLM in a rat model.

Materials and methods: PF was induced in Wistar rats by a single dose of BLM (7.5 U/kg) on the 7th day. The rats were then randomly assigned to six groups: control, BLM, and four treatment groups receiving BLM + different doses of TAIC or TA alone (28 days, gavage). Animals were sacrificed on the 29th day and lung samples were collected to assess histopathological alterations and biochemical parameters such as lung index, nitric oxide (NO), malondialdehyde (MDA), hydroxyproline (HP), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and tumor necrosis factor- α (TNF-α).

Results: The results demonstrated that the TAIC complex significantly attenuated BLM-induced elevation in lung index as well as the levels of MDA, NO, HP, and TNF-α. Additionally, TAIC enhanced the activities of key antioxidant enzymes, including CAT, SOD, GPx, and increased GSH content. This complex also inhibited the infiltration of fibroblasts and inflammatory cells, thereby preventing alveolar thickening. Notably, the effect of TA at 400 mg/kg, while beneficial, was slightly less pronounced compared to the TAIC complex at the same dosage.

Conclusion: The results revealed that TAIC hasa protective effect on BLM -induced pulmonary fibrosis.

Objective: Rising childhood obesity is a global concern, with environmental tobacco exposure as a potential risk factor. However, the mechanisms linking secondhand smoke and e-cigarette aerosol to adolescent obesity remain unclear.

Methods: We analyzed data from 968 participants aged 3- 19 years in the NHANES 2017- 2020 cycles. Passive exposure was assessed using self-reported household exposure and objectively measured serum cotinine levels. Multivariate logistic regression was used to evaluate the associations between exposure categories and overweight/obesity status. Cotinine-related molecular targets were identified through network pharmacology and toxicology analyses, with protein-protein interaction networks, enrichment analyses, and molecular docking used to explore relevant pathways.

Results: Compared with unexposed individuals, participants exposed to both secondhand smoke and e-cigarette aerosols had significantly greater odds of overweight or obesity (adjusted odds ratio [aOR] = 3.9; 95% CI: 1.4-11.0; p = 0.009). Serum cotinine levels were also positively associated with obesity risk in a dose-dependent manner, with those in the highest quartile (Q4) showing aOR = 3.8 (95% CI: 2.1-6.8; p < 0.001) compared with those in Q1. Network analyses identified CHRNA2 and CHRNB2 as key targets involved in cholinergic signaling and metabolic regulation. Cotinine demonstrated strong binding affinity to these targets in molecular docking, supporting its potential biological activity beyond being a nicotine biomarker.

Conclusion: Passive nicotine exposure is significantly associated with overweight or obesity among adolescents, and cotinine may be involved in relevant biological pathways related to energy regulation. These findings may inform future research and preventive strategies.

Objective: Carbon monoxide (CO) poisoning impairs oxygen transport by forming carboxyhemoglobin (COHb). Normobaric oxygen (NBO) is standard therapy, but its COHb elimination rate is slow. This study compared the effectiveness of NBO, NIMV, and EzPAP in reducing COHb levels in acute CO poisoning.

Materials and methods: This prospective cohort study included patients with acute CO poisoning in an emergency department. Participants received one of three treatment modalities: standard NBO therapy, NIMV with positive pressure support, or the EzPAP system. COHb levels were recorded at baseline, 30 min, and 60 min after initiation of therapy. The primary outcome was the change in COHb concentration over time.

Results and discussion: A total of 66 patients were included in the study (NIMV: n = 29, EzPAP: n = 18, and NBO: n = 19). Significant differences were observed in symptom distribution, with headache more frequent in the EzPAP and NBO groups and dyspnea more common in NIMV and EzPAP groups (p < 0.001). Baseline COHb levels did not differ between groups (p = 0.849). At 30 and 60 min, NIMV achieved significantly greater COHb reduction compared to NBO (p < 0.001), while EzPAP showed superiority over NBO at 60 min (p = 0.031). Pairwise analyses indicated NIMV was also superior to EzPAP at 60 min (p = 0.003).

Conclusions: While NBO remains the standard therapy, this study suggests NIMV - and to a lesser extent, EzPAP - may serve as effective adjuncts in the management of CO poisoning. These findings provide a rationale for further randomized controlled trials.

Objective: Endosulfan, an organochlorine pesticide, consists of two isomers (α-Endosulfan and β-Endosulfan) and a primary metabolite, Endosulfan sulfate (END-SO₄). Due to its pervasive environmental contamination and harmful effects-such as neurotoxicity, endocrine disruption, and reproductive toxicity in humans-END was included in the Stockholm Convention on Persistent Organic Pollutants (Annex A) in 2011, leading to its prohibition in many regions. The toxic effects of END have been extensively studied, but the specific mechanism of its lung injury remains unknown. This study explores how α/β-Endosulfan and END-SO₄ may induce lung injury using in silico approaches.

Methods: Toxicity prediction was performed using STopTox, ADMETlab 3.0, and Deep-PK. Network toxicology analyses were conducted via the Comparative Toxicogenomic Database, DAVID, Metascape, GeneMANIA, STRING, and Cytoscape. AUTODOCK was used for molecular docking of α/β-END and END-SO₄ with key targets.

Results: The study identified 4658 targets for α/β-END and 21 for END-SO4, with 126 linked to lung injury. Of these, 53 targets were common to both the compounds and lung injury, primarily associated with inflammation and fibrosis. Centrality analysis highlighted IL1B, TNF, and IL6 as key targets. Docking results showed binding affinities ranging from -4.53 to -8.32 kcal/mol between α/β-END, END-SO₄, and IL1B/TNF.

Conclusion: These findings suggest that exposure to α/β-END and END-SO₄ may trigger inflammation and fibrosis, contributing to lung injury. These findings provide a basis for further experimental studies aimed at validating the role of IL1B and TNF in α/β-END-induced lung injury.

Objective: Cyclin-dependent kinase inhibitor 2 A, CDKN2A/p16INK4a (p16), is a gene involved in regulating the cell cycle, cellular senescence, and inflammatory responses. The role of p16 in pulmonary immune-inflammatory and cellular senescence responses to low-dose, sub-chronic environmental tobacco smoke (ETS) is not known. We hypothesized that p16-deficient (knockout, KO) mice would exhibit adverse lung responses compared to wild-type (WT) mice, characterized by a decline in lung function, impaired immune responses, lung remodeling, and dysregulated inflammatory responses at low-level ETS exposure.

Materials and methods: C57BL/6J (WT) and p16 knockout, p16^-/-, were exposed to low dose ETS [10 mg/m³ total particulate matter (TPM)] for 3 months. Bronchoalveolar fluid (BALF) and lung tissue were used in subsequent analyses.

Results: Histological analysis revealed mild alveolar simplification in p16 KO mice compared to WT mice. CDKN2A/p16 KO BALF did not have the same immune cell infiltration or cytokine response as the WT counterparts, where IL-17A, TNF-α, and GM-CSF were significantly elevated, indicating impaired immune response with p16 deficiency. Proteomic analysis revealed significantly elevated proteins related to inflammation, extracellular matrix remodeling, cellular metabolism, pro-senescence, and oxidative stress in p16 KO mice (Kynu, Col5a3, Lamtor3). NLRP3 and PTGS2 (COX-2) activation z-scores were lower in p16 KO mice, while IL33 and CCR5 activation z-scores were higher compared to WT mice.

Discussion: Thus, p16 deficiency amplifies ETS-induced alveolar architecture, impaired immune responses, and altered inflammatory pathways, contributing to heightened susceptibility to emphysema-like changes compared to WT mice even at low ETS levels. This study revealed that p16 deletion alters response to low-level ETS, not necessarily by amplifying the classic 'damage response' but by modifying immune and senescence signaling in the lungs.

Conclusion: Overall, p16 has a complex and nuanced protective role in lung health, and careful targeting p16-related pathways could offer therapeutic strategies for mitigating chronic lung diseases.

The main route of occupational exposure to nanomaterials is inhalation. Sputum and nasal lavage are the most important biological samples to analyze lung-specific biomarkers in occupational exposure. So, the aim of this study is to conduct a mixed-method systematic review with meta-synthesis and meta-analysis for assessment of sputum and nasal lavage lung-specific biomarkers in occupational exposure to nanomaterials. This systematic review was conducted through the end of June 2025. Search was done using 'Biomarkers', 'Occupational exposure', 'Sputum', 'Nanomaterials' and 'Nasal Lavage' keywords on PubMed, Scopus and WOS. After the data extraction, qualitative data was used to draw a qualitative model. Comprehensive Meta-Analysis Software (CMA) was used for meta-analysis and the pooled mean concentration of the biomarkers were calculated by the random effect model (REM). Thirty-three studies were primarily achieved, and six studies were finally analyzed. Pro-inflammatory, inflammatory, oxidative stress, cancer/fibrosis and cardiovascular biomarkers were the most important biomarkers investigated. Inflammatory biomarkers including IL-6, IL-8, IL-1β and TNF-α were involved better than other inflammatory biomarkers in nasal, in occupational exposure to nanomaterials. The pooled mean concentration of sputum inflammatory biomarkers interleukin including IL-1β, IL-2, IL-4, IL5, IL-6, IL-8 was estimated 404.76, 196.9, 156.47, 219.26, 33.98 and 2344.42 pg/mL, respectively. Moreover, concentration of Nasal lavage inflammatory biomarkers interleukin including IL-1β, IL-6, and IL-8 were 1.438, 0.911 and 17.847 pg/mL, respectively. Due to a lack of information about OEL for nanomaterials, evaluating the occupational exposure to them through measuring the level of specific biomarkers, especially in the upper respiratory system, requires more studies.

Objective: Allergic rhinitis (AR), an allergen-driven chronic inflammatory disorder of nasal mucosa, is characterized by airway inflammation as its cardinal pathological manifestation. While acetylation is known to regulate airway inflammation, its mechanistic involvement in AR-related inflammation remains elusive. This study aims to investigate the acetylation-dependent mechanisms governing airway inflammation in AR.

Materials and methods: RNA-seq analysis identified differentially expressed genes in peripheral blood of AR patients and healthy controls. Ovalbumin-sensitized BALB/c mice were performed as the AR mouse model. Airway inflammation was assessed by measuring inflammatory cytokine levels, inflammatory cell numbers, macrophage counts in whole lung lavage fluid (WLLF), and specific IgE levels in plasma using ELISA and Diff-Quick staining. The underlying mechanism was investigated through Western blotting, immunoprecipitation (IP), and Co-IP.

Results: GNG3 expression was significantly increased in AR patients and the AR mouse model. Knockdown of GNG3 significantly reduced airway inflammation and inhibited NF-κB pathway activation in the AR mouse model. CREBBP overexpression enhanced GNG3 protein stability, and CREBBP mRNA expression was significantly increased in patients with AR and positively correlated with GNG3 expression. Furthermore, GNG3 overexpression restored airway inflammation that was suppressed by CREBBP knockdown in the AR mouse model.

Conclusion: These results demonstrate that CREBBP aggravated airway inflammation in AR by activating the NF-κB pathway via GNG3 upregulation mediated by GNG3 acetylation.

Inhalation of emissions from combustion events such as military burn pits and wildland-urban interface fires result in exposures to complex aerosols that may cause adverse health effects. A surrogate combustion generator was created to study these events. A pellet stove was modified to burn diverse fuels comprised of materials found in burn pits (plastic, rubber, and wood). Jet fuel (JF) was added during combustion. The purpose of this project was to: 1) operate the generator over diverse parameters; and 2) characterize the resultant emissions. Pellet combustion (8 g/minute; range: 1-34) ± JF (0.2 mL/minute; range: 0-1) was conducted at fixed rates. Real-time and off-line aerosol characterizations (size distributions, concentrations, morphology) and chemical measures (total and speciation of volatiles, organics, elementals) with subsequent analytic methodology were performed. Pellet combustion produced an average particle concentration of 7.0e+6±1.1e+6 #/cc, and a total volatile organic compound concentration (TVOC) of 0.97+0.41 parts per million (PPM). The addition of JF accelerated the combustion process and increased the total particle counts to 4.5e+7±8.3e+6 #/cc, but decreased the TVOC to 0.63±0.26 ppm. Ultrafine particles were predominantly generated with similar count median diameters (<100 nm) and polydisperse distributions (GSD>1.5). Chemical speciation revealed potential human carcinogens (formaldehyde, acetaldehyde) and the addition of JF resulted in a >40-fold drop in organic carbon constituents. Adding plastic and rubber into the pellet mixture resulted in emissions containing 4% methyl-methacrylate and 10% methyl-isobutyl-ketones. Future experiments will assess diverse wood varieties, synthetic building constituents, and asses the biological effects that follow these inhalation exposures.

Objective: Iraqi automobiles use some of the poorest quality fuel in the world, characterized by extremely high sulfur content. In this study, we aim to investigate the immunological impact of traffic-related air pollution (TRAP) on individuals residing in the Kurdistan Region of Iraq.

Materials and methods: This prospective cross-sectional study (June 2021 and January 2022) assessed the immunological profile of 77 male participants in Sulaymaniyah Governorate who were grouped based on predefined exposure zones; High TRAP Group (n = 46) from urban areas with high exposure to TRAP and Low TRAP Group (n = 31) from rural areas with low exposure. An Aeroqual Series 500 monitor was used to estimate 24-hour arithmetic mean concentrations of PM1.0, PM2.5, and PM10 in the two exposure zones.

Results and discussion: Age distribution was comparable between the groups. Participants of High TRAP Group had significantly lower total lymphocyte counts (1.09 ± 0.36 vs. 1.90 ± 0.41, p < 0.001), T-cell (601.41 ± 60.02 vs. 799.80 ± 56.04; p < 0.001), B-cell levels (113.05 ± 48.23 vs. 230.68 ± 57.90; p < 0.001), IgG (11.94 ± 2.52 vs. 13.35 ± 2.77; p = 0.024), and IgM levels (0.96 ± 0.40 vs. 1.4 ± 0.66, p < 0.001) compared to Low TRAP Group. No significant differences were found in total WBC, granulocytes, or IgA levels (p > 0.05). The presence of inflammatory diseases (mostly thyroiditis) was significantly more common among the individuals of High TRAP Group (13, 28.26% vs. 3, 9.68%; p = 0.048).

Conclusion: Individuals with high exposure to TRAP are associated with significant reductions in lymphocyte count, IgM and IgG levels.

The mucosal origins hypothesis posits that environmental inhalant exposures, including cigarette smoke (CS) and crystalline silica (c-silica), trigger immune responses in the lung mucosa, an extra-articular site, which precede initiating events of rheumatoid arthritis (RA) pathogenesis in distant joints. Epidemiological data strongly associates these exposures with RA risk, especially in genetically susceptible individuals carrying HLA-DRB1 alleles, and with the production of autoantibodies such as anti-citrullinated peptide antibodies (ACPA) and rheumatoid factor (RF). However, establishing causality remains challenging due to unsynchronized exposure and disease onset and the lack of suitable animal models to study early disease events. This review synthesizes evidence linking inhalant exposures to RA, focusing on CS and c-silica, and evaluates experimental animal models used to investigate disease initiation and progression in the context of inhalant exposures. While models like collagen-induced arthritis (CIA) replicate joint pathology, they often fail to capture the lung-joint axis and gene-environment interactions critical for RA onset. We highlight the need for refined models with genetic susceptibility to subclinical autoimmunity to better mimic human RA, emphasizing the importance of standardized exposure protocols to address variability in outcomes. These advancements are crucial for elucidating mechanisms of inhalant exposure-induced RA and developing preventive strategies.