A comprehensive toxicological analysis of panel of unregulated e-cigarettes to human health.

Electronic cigarettes, commonly referred to as e-cigarettes have gained popularity over recent years especially among young individuals. In the light of the escalating prevalence of the use of these products and their potential for long-term health effects, in this study as the first of its kind a comprehensive toxicological profiling of the liquid from a panel of unregulated e-cigarettes seized in the UK was undertaken using an in vitro co-culture model of the upper airways. The data showed that e-cigarettes caused a dose dependent increase in cell death and inflammation manifested by enhanced release of IL1ß and IL6. Furthermore, the e-cigarettes induced oxidative stress as demonstrated by a reduction of intracellular glutathione and an increase in generation of reactive oxygen species. Moreover, the assessment of genotoxicity showed significant DNA strand breaks (following exposure to Tigerblood flavoured e-cigarette). Moreover, relevant to the toxicological observations, was the detection of varying and frequently high levels of hazardous metals including cadmium, copper, nickel and lead. This study highlights the importance of active and ongoing collaborations between academia, governmental organisations and policy makers (Trading standards, Public Health) and national health service in tackling vape addiction and better informing the general public regarding the risks associated with e-cigarette usage.

Proton therapy for breast cancer: Reducing toxicity.

Radiotherapy is a crucial component in the holistic management of breast cancer, with approximately 60% of individuals diagnosed with breast cancer requiring this treatment. As the survival rate of individuals with breast cancer has significantly increased, there is a growing focus on the long-term well-being of patients. Proton therapy (PT) is a new and rapidly developing radiotherapy method. In comparison with conventional photon therapy, PT offers the benefits of decreased radiation toxicity and increased dosage in the designated region. This can extend patients' lifespan and enhance their overall well-being. The present analysis examines the function of PT in diminishing the harmful effects of radiation in cases of breast cancer, while also providing a brief overview of the future potential and obstacles associated with PT for breast cancer.

Investigation of pulmonary inflammatory responses following intratracheal instillation of and inhalation exposure to polypropylene microplastics.

BACKGROUND: Microplastics have been detected in the atmosphere as well as in the ocean, and there is concern about their biological effects in the lungs. We conducted a short-term inhalation exposure and intratracheal instillation using rats to evaluate lung disorders related to microplastics. We conducted an inhalation exposure of polypropylene fine powder at a low concentration of 2 mg/m3 and a high concentration of 10 mg/m3 on 8-week-old male Fischer 344 rats for 6 h a day, 5 days a week for 4 weeks. We also conducted an intratracheal instillation of polypropylene at a low dose of 0.2 mg/rat and a high dose of 1.0 mg/rat on 12-week-old male Fischer 344 rats. Rats were dissected from 3 days to 6 months after both exposures, and bronchoalveolar lavage fluid (BALF) and lung tissue were collected to analyze lung inflammation and lung injury. RESULTS: Both exposures to polypropylene induced a persistent influx of inflammatory cells and expression of CINC-1, CINC-2, and MPO in BALF from 1 month after exposure. Genetic analysis showed a significant increase in inflammation-related factors for up to 6 months. The low concentration in the inhalation exposure of polypropylene also induced mild lung inflammation. CONCLUSION: These findings suggest that inhaled polypropylene, which is a microplastic, induces persistent lung inflammation and has the potential for lung disorder. Exposure to 2 mg/m3 induced inflammatory changes and was thought to be the Lowest Observed Adverse Effect Level (LOAEL) for acute effects of polypropylene. However, considering the concentration of microplastics in a real general environment, the risk of environmental hazards to humans may be low.

A Fatal Consequence: Amiodarone-Induced Multiorgan Toxicity.

Amiodarone is commonly used nowadays for the treatment of atrial fibrillation (AF). The wide use of this medication has led to the occurrence of adverse events, including pulmonary toxicity, hepatotoxicity, thyroid dysfunction, and many others. Higher doses of Amiodarone of ≥400 mg/day have been linked to increased complications. We present a case of a 70-year-old male with multivessel coronary artery disease (CAD) with ischemic cardiomyopathy and severe peripheral artery disease (PAD) who underwent an elective left femoral to posterior tibial bypass surgery followed by percutaneous coronary intervention (PCI) complicated by new-onset AF. The patient was loaded with 150 mg of intravenous (IV) Amiodarone followed by 360 mg infusion over six hours for chemical cardioversion. The patient was then maintained on oral Amiodarone 400 mg/day until the day of presentation when he complained of progressive dyspnea. Imaging was significant for diffuse ground glass opacities and interstitial thickening. The echocardiogram revealed an improved ejection fraction (EF) of 40% from 20%. The patient had worsening oxygenation despite adequate IV diuresis and developed severe acute respiratory distress syndrome (ARDS) requiring mechanical ventilation (MV). A bronchoscopy with bronchoalveolar lavage (BAL) showed diffuse alveolar hemorrhage (DAH) with a high lymphocyte count and negative infectious disease testing. Lab tests revealed elevated liver enzyme levels. There were also changes in thyroid function from baseline with elevated free T4 at 1.83 ng/dL (0.8-1.4 ng/dL), suppressed thyroid stimulating hormone (TSH) at 0.109 mIU/mL (0.4-4 mIU/mL), negative anti-thyroglobulin (TG) antibodies, and anti-thyroid peroxidase (TPO) antibodies indicating a type 2 Amiodarone-induced thyrotoxicosis. Unfortunately, the patient's condition deteriorated further despite appropriate treatment, and it was ultimately followed by his demise. Severe, fatal cases of Amiodarone toxicity are scarce, but more reports are being seen. We strongly believe clinicians should have a high index of suspicion for Amiodarone-related adverse events in elderly males with cardiopulmonary comorbidities. It is imperative to have an increased understanding, greater vigilance, and closer monitoring of pulmonary function tests (PFTs), laboratory tests, and imaging studies.

Incidence and Clinical Characteristics of Drug-Induced Lung Disease Among Chemotherapy Recipients.

Background Chemotherapeutic agents treat cancer and some inflammatory diseases due to their immunosuppressive effects. While effective, these drugs can cause drug-induced lung disease (DILD), a serious adverse effect with limited data regarding its incidence and clinical presentation. Methods This retrospective study included 20 patients diagnosed with DILD out of 1,231 patients treated with chemotherapeutic agents who presented with symptoms such as cough, fever, dyspnea, and chest pain at an oncology outpatient clinic. Patients underwent assessments including clinical examination, chest radiography, high-resolution computed tomography, and, in some cases, video-assisted thoracoscopic surgery. A statistical analysis was performed to determine the incidence and evaluate the clinical characteristics of DILD. Results The incidence of DILD among patients treated with chemotherapeutic agents was 0.27%. The female/male ratio was 11/9, with a mean age of 53.2 years. Common symptoms included cough (70%), dyspnea (60%), fever (50%), and sputum production (40%). Imaging revealed pleural effusion, reticular patterns, and consolidation in varying proportions. Common agents causing pulmonary toxicity included bleomycin, cyclophosphamide, and methotrexate, among others. Importantly, 95% of patients showed improvement with steroid treatment, although statistical significance was not achieved (p > 0.05). Conclusion The findings highlight the need for heightened awareness and monitoring of DILD in patients receiving chemotherapeutic treatments. Early diagnosis and prompt treatment initiation are crucial to managing this potentially severe complication. This study underscores the importance of considering pulmonary risks when prescribing chemotherapeutic agents and provides foundational data for future research.

An in vitro comparison of the toxicological profiles of ground tire particles (TP) and actual tire and road wear particles (TRWP) emissions.

There is currently limited data on the potential effects of tire and road wear particles (TRWP) on human health. TRWP include tire fragments, but also road wear materials, dust, adsorbed gaseous pollutants and different types of inclusions that could affect their hazard profiles. Due to their availability and lower complexity, ground tire particles (TP) are often used in toxicological studies. However, this makes it difficult to draw firm conclusions about the potential hazard of actual TRWP. Here, we compared the in vitro toxicological profile of ground TP and actual TRWP emissions of similar size collected from road traffic. For this purpose, TP and TRWP were separately incubated with alveolar macrophages for 24 h, and the cellular response was evaluated in terms of cytotoxicity, proinflammatory response and oxidative stress. Both TP and TRWP induced neither significant cytotoxicity nor oxidative stress, but triggered a concentration-dependent proinflammatory response, as evidenced by increased TNF-α production. The level of TNF-α production was slightly higher with TRWP than with TP, independent of the particle dose. All in all, the pulmonary toxicity of TRWP could be due primarily to the tire tread inclusions and only marginally to other particle components (i.e. road wear materials, dust …). Although these preliminary results need to be confirmed by further analysis, they could be useful for tire manufacturers in the production of safer-by-design tires.

Realistic Nanoplastics Induced Pulmonary Damage via the Crosstalk of Ferritinophagy and Mitochondrial Dysfunction.

The smaller size fraction of plastics may be more substantially existing and detrimental than larger-sized particles. However, reports on nanoplastics (NPs), especially their airborne occurrences and potential health hazards to the respiratory system, are scarce. Previous studies limit the understanding of their real respiratory effects, since sphere-type polystyrene (PS) nanoparticles differ from NPs occurring in nature with respect to their physicochemical properties. Here, we employ a mechanical breakdown method, producing NPs directly from bulk plastic, preserving NP properties in nature. We report that among four relatively high abundance NP materials PS, polyethylene terephthalate (PET), polyvinyl chloride (PVC), and polyethylene (PE) with a size of 100 nm, PVC induced slightly more severe lung toxicity profiles compared to the other plastics. The lung cytotoxicity of NPs is higher than that of commercial PS NPs and comparable to natural particles silicon dioxide (SiO2) and anatase titanium dioxide (TiO2). Mechanistically, BH3-interacting domain death agonist (Bid) transactivation-mediated mitochondrial dysfunction and nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy or ferroptosis are likely common mechanisms of NPs regardless of their chemical composition. This study provides relatively comprehensive data for evaluating the risk of atmospheric NPs to lung health.

Epithelium-derived exosomes promote silica nanoparticles-induced pulmonary fibroblast activation and collagen deposition via modulating fibrotic signaling pathways and their epigenetic regulations.

BACKGROUND: In the context of increasing exposure to silica nanoparticles (SiNPs) and ensuing respiratory health risks, emerging evidence has suggested that SiNPs can cause a series of pathological lung injuries, including fibrotic lesions. However, the underlying mediators in the lung fibrogenesis caused by SiNPs have not yet been elucidated. RESULTS: The in vivo investigation verified that long-term inhalation exposure to SiNPs induced fibroblast activation and collagen deposition in the rat lungs. In vitro, the uptake of exosomes derived from SiNPs-stimulated lung epithelial cells (BEAS-2B) by fibroblasts (MRC-5) enhanced its proliferation, adhesion, and activation. In particular, the mechanistic investigation revealed SiNPs stimulated an increase of epithelium-secreted exosomal miR-494-3p and thereby disrupted the TGF-ß/BMPR2/Smad pathway in fibroblasts via targeting bone morphogenetic protein receptor 2 (BMPR2), ultimately resulting in fibroblast activation and collagen deposition. Conversely, the inhibitor of exosomes, GW4869, can abolish the induction of upregulated miR-494-3p and fibroblast activation in MRC-5 cells by the SiNPs-treated supernatants of BEAS-2B. Besides, inhibiting miR-494-3p or overexpression of BMPR2 could ameliorate fibroblast activation by interfering with the TGF-ß/BMPR2/Smad pathway. CONCLUSIONS: Our data suggested pulmonary epithelium-derived exosomes serve an essential role in fibroblast activation and collagen deposition in the lungs upon SiNPs stimuli, in particular, attributing to exosomal miR-494-3p targeting BMPR2 to modulate TGF-ß/BMPR2/Smad pathway. Hence, strategies targeting exosomes could be a new avenue in developing therapeutics against lung injury elicited by SiNPs.

Differences in the anatomy and physiology of the human and rat respiratory tracts and impact on toxicological assessments.

Inhalation is a critical route through which substances can exert adverse effects in humans; therefore, it is important to characterize the potential effects that inhaled substances may have on the human respiratory tract by using fit for purpose, reliable, and human relevant testing tools. In regulatory toxicology testing, rats have primarily been used to assess the effects of inhaled substances as they-being mammals-share similarities in structure and function of the respiratory tract with humans. However, questions about inter-species differences impacting the predictability of human effects have surfaced. Disparities in macroscopic anatomy, microscopic anatomy, or physiology, such as breathing mode (e.g., nose-only versus oronasal breathing), airway structure (e.g., complexity of the nasal turbinates), cell types and location within the respiratory tract, and local metabolism may impact inhalation toxicity testing results. This review shows that these key differences describe uncertainty in the use of rat data to predict human effects and supports an opportunity to harness modern toxicology tools and a detailed understanding of the human respiratory tract to develop testing approaches grounded in human biology. Ultimately, as the regulatory purpose is protecting human health, there is a need for testing approaches based on human biology and mechanisms of toxicity.

Impact of aging and ergothioneine pre-treatment on naphthalene toxicity in lung.

Aging increases susceptibility to lung disease, but the topic is understudied, especially in relation to environmental exposures with the bulk of rodent studies using young adults. This study aims to define the pulmonary toxicity of naphthalene (NA) and the impacts of a dietary antioxidant, ergothioneine (ET), in the liver and lungs of middle-aged mice. NA causes a well-characterized pattern of conducting airway epithelial injury in the lung in young adult mice, but NA's toxicity has not been characterized in middle-aged mice, aged 1-1.5 years. ET is a dietary antioxidant that is synthesized by bacteria and fungi. The ET transporter (ETT), SLC22A4, is upregulated in tissues that experience high levels of oxidative stress. In this study, middle-aged male and female C57BL/6 J mice, maintained on an ET-free synthetic diet from conception, were gavaged with 70 mg/kg of ET for five consecutive days. On day 8, the mice were exposed to a single intraperitoneal NA dose of 50, 100, 150, or 200 mg/kg. At 24 hours post NA injection samples were collected and analyzed for ET concentration and reduced (GSH) and oxidized glutathione (GSSG) concentrations. Histopathology, morphometry, and gene expression were examined. Histopathology of mice exposed to 100 mg/kg of NA suggests reduction in toxicity in the terminal airways of both male (p ≤ 0.001) and female (p ≤ 0.05) middle-aged mice by the ET pretreatment. Our findings in this study are the first to document the toxicity of NA in middle-aged mice and show some efficacy of ET in reducing NA toxicity.

The Effects of Endoplasmic Reticulum Stress via Intratracheal Instillation of Water-Soluble Acrylic Acid Polymer on the Lungs of Rats.

Polyacrylic acid (PAA), an organic chemical, has been used as an intermediate in the manufacture of pharmaceuticals and cosmetics. It has been suggested recently that PAA has a high pulmonary inflammatory and fibrotic potential. Although endoplasmic reticulum stress is induced by various external and intracellular stimuli, there have been no reports examining the relationship between PAA-induced lung injury and endoplasmic reticulum stress. F344 rats were intratracheally instilled with dispersed PAA (molecular weight: 269,000) at low (0.5 mg/mL) and high (2.5 mg/mL) doses, and they were sacrificed at 3 days, 1 week, 1 month, 3 months and 6 months after exposure. PAA caused extensive inflammation and fibrotic changes in the lungs' histopathology over a month following instillation. Compared to the control group, the mRNA levels of endoplasmic reticulum stress markers Bip and Chop in BALF were significantly increased in the exposure group. In fluorescent immunostaining, both Bip and Chop exhibited co-localization with macrophages. Intratracheal instillation of PAA induced neutrophil inflammation and fibrosis in the rat lung, suggesting that PAA with molecular weight 269,000 may lead to pulmonary disorder. Furthermore, the presence of endoplasmic reticulum stress in macrophages was suggested to be involved in PAA-induced lung injury.

Subchronic toxicity study of indium-tin oxide nanoparticles following intratracheal administration into the lungs of rats.

OBJECTIVES: We aimed to analyze the subchronic toxicity and tissue distribution of indium after the intratracheal administration of indium-tin oxide nanoparticles (ITO NPs) to the lungs of rats. METHODS: Male Wistar rats were administered a single intratracheal dose of 10 or 20 mg In/kg body weight (BW) of ITO NPs. The control rats received only an intratracheal dose of distilled water. A subset of rats was periodically euthanized throughout the study from 1 to 20 weeks after administration. Indium concentrations in the serum, lungs, mediastinal lymph nodes, kidneys, liver, and spleen as well as pathological changes in the lungs and kidneys were determined. Additionally, the distribution of ionic indium and indium NPs in the kidneys was analyzed using laser ablation-inductively coupled plasma mass spectrometry. RESULTS: Indium concentrations in the lungs of the 2 ITO NP groups gradually decreased over the 20-week observation period. Conversely, the indium concentrations in the mediastinal lymph nodes of the 2 ITO groups increased and were several hundred times higher than those in the kidneys, spleen, and liver. Pulmonary and renal toxicities were observed histopathologically in both the ITO groups. Both indium NPs and ionic indium were detected in the kidneys, and their distributions were similar to the strong indium signals detected at the sites of inflammatory cell infiltration and tubular epithelial cells. CONCLUSIONS: Our results demonstrate that intratracheal administration of 10 or 20 mg In/kg BW of ITO NPs in male rats produces pulmonary and renal toxicities.

The pulmonary protective potential of vanillic acid-loaded TPGS-liposomes: modulation of miR-217/MAPK/NF-κb signalling pathway.

The aim is to investigate the possible pulmonary protective effect of vanillic acid (VA) in liposome-TPGS nanoparticles, to overcome VA's poor bioavailability. VA was successfully extracted. Liposomes were prepared using thin film hydration. Central composite design was adopted for optimisation of liposomes to get the maximum entrapment efficiency (EE%) and the minimum mean diameter, where the liposomes were further modified with TPGS, and tested for PDI, zeta-potential, and in-vitro drug release. In-vivo study on mice with LPS-acute pulmonary toxicity was tested. TPGS-modified VA-liposomes showed EE% of 69.35 ± 1.23%, PS of 201.7 ± 3.23 nm, PDI of 0.19 ± 0.02, and zeta-potential of -32.2 ± 0.32 mv. A sustained drug release of the TPGS-modified VA-liposomes was observed compared to standard VA, and a pulmonary-protective effect through decreasing miR-217 expression with subsequent anti-inflammatory effect through suppression of MAPK and PI3K/NF-κB pathways was also demonstrated in the current study. TPGS-modified VA-liposomes showed an enhanced bioavailability and a sustained drug release with promising pulmonary protective effects against acute pulmonary injury diseases.

Tobramycin Reduces Pulmonary Toxicity of Polymyxin B via Inhibiting the Megalin-Mediated Drug Uptake in the Human Lung Epithelial Cells.

Accumulation of polymyxins in the lung epithelial cells can lead to increased mitochondrial oxidative stress and pulmonary toxicity. Aminoglycosides and polymyxins are used, via intravenous and pulmonary delivery, against multidrug-resistant Gram-negative pathogens. Our recent in vitro and animal studies demonstrated that the co-administration of polymyxins with aminoglycosides decreases polymyxin-induced pulmonary toxicity. The aim of this study was to investigate the in vitro transport and uptake of polymyxin B and tobramycin in human lung epithelial Calu-3 cells and the mechanism of reduced pulmonary toxicity resulting from this combination. Transport, intracellular localization, and accumulation of polymyxin B and tobramycin were investigated using doses of 30 mg/L polymyxin B, 70 mg/L tobramycin, and the combination of both. Adding tobramycin significantly (p < 0.05) decreased the polymyxin B-induced cytotoxicity in Calu-3 cells. The combination treatment significantly reduced the transport and uptake of polymyxin B and tobramycin in Calu-3 cells, compared to each drug alone, which supported the reduced pulmonary toxicity. We hypothesized that cellular uptake of polymyxin B and tobramycin shared a common transporter, megalin. We further investigated the megalin expression of Calu-3 cells using confocal microscopy and evaluated megalin activity using a megalin substrate, FITC-BSA, and a megalin inhibitor, sodium maleate. Both polymyxin B and tobramycin significantly inhibited FITC-BSA uptake by Calu-3 cells in a concentration-dependent manner. Sodium maleate substantially inhibited polymyxin B and tobramycin transport and cellular accumulation in the Calu-3 cell monolayer. Our study demonstrated that the significantly reduced uptake of polymyxin B and tobramycin in Calu-3 cells is attributed to the mechanism of action that determines that polymyxin B and tobramycin share a common transporter, megalin.

Symptomatic Pneumonitis With Durvalumab After Concurrent Chemoradiotherapy in Unresectable Stage III NSCLC.

Introduction: In the placebo-controlled, phase 3 PACIFIC trial, durvalumab significantly prolonged progression-free survival (PFS) (p < 0.0001) and overall survival (OS) (p = 0.00251) in patients with unresectable stage III NSCLC and no progression after platinum-based concurrent chemoradiotherapy (cCRT). Pneumonitis or radiation pneumonitis (PRP) was common in both arms. We report exploratory analyses evaluating the association of symptomatic (grade ≥2) PRP (G2+PRP) with baseline factors and clinical outcomes. Methods: Patients with WHO performance status of 0 or 1 were randomized (2:1) to 12 months of durvalumab or placebo, 1 to 42 days after cCRT. Associations between baseline factors and on-study G2+PRP in durvalumab-treated patients were investigated using univariate and multivariate logistic regression. PFS and OS were analyzed using Cox proportional hazards models adjusted for time-dependent G2+PRP plus covariates for randomization stratification factors without and with additional baseline factors. Results: On-study G2+PRP occurred in 94 of 475 (19.8%) and 33 of 234 patients (14.1%) on durvalumab and placebo, respectively (median follow-up, 25.2 mo); grade greater than or equal to 3 PRP was uncommon (4.6% and 4.7%, respectively). Time to onset and resolution of G2+PRP was similar with durvalumab and placebo. Univariate and multivariate analyses identified patients treated in Asia, those with stage IIIA disease, those with performance status of 1, and those who had not received induction chemotherapy as having a higher risk of G2+PRP. PFS and OS benefit favoring durvalumab versus placebo was maintained regardless of time-dependent G2+PRP. Conclusions: Factors associated with higher risk of G2+PRP with durvalumab after cCRT were identified. Clinical benefit was maintained regardless of on-study G2+PRP, suggesting the risk of this event should not deter the use of durvalumab in eligible patients with unresectable stage III NSCLC.

Drug-induced interstitial lung disease: a narrative review of a clinical conundrum.

INTRODUCTION: Drug-induced interstitial lung disease (DI-ILD) is increasing in incidence, due to the use of many new drugs across a broad range of cancers and chronic inflammatory diseases. The presentation and onset of DI-ILD are variable even for the same drug across different individuals. Clinical suspicion is essential for identifying these conditions, with timely drug cessation an important determinant of outcomes. AREAS COVERED: This review provides a comprehensive and up-to-date summary of epidemiology, risk factors, pathogenesis, diagnosis, treatment, and prognosis of DI-ILD. Relevant research articles from PubMed and Medline searches up to September 2023 were screened and summarized. Specific drugs including immune checkpoint inhibitors, CAR-T cell therapy, methotrexate, and amiodarone are discussed in detail. The potential role of pharmacogenomic profiling for lung toxicity risk is considered. EXPERT OPINION: DI-ILD is likely to be an increasingly important contributor to respiratory disability in the community. These conditions can negatively impact quality of life and patient longevity, due to associated respiratory compromise as well as cessation of evidence-based therapy for the underlying disease. This clinical conundrum is relevant to all areas of medicine, necessitating increased understanding and greater vigilance for drug-related lung toxicity.

The role of lysosomes in airborne particulate matter-induced pulmonary toxicity.

An investigation of the potential role of lysosomes in airborne particulate matter (APM) induced health risks is essential to fully comprehend the pathogenic mechanisms of respiratory diseases. It is commonly accepted that APM-induced lung injury is caused by oxidative stress, inflammatory responses, and DNA damage. In addition, there exists abundant evidence that changes in lysosomal function are essential for cellular adaptation to a variety of particulate stimuli. This review emphasizes that disruption of the lysosomal structure/function is a key step in the cellular metabolic imbalance induced by APMs. After being ingested by cells, most particles are localized within lysosomes. Thus, lysosomes become the primary locus where APMs accumulate, and here they undergo degradation and release toxic components. Recent studies have provided incontrovertible evidence that a wide variety of APMs interfere with the normal function of lysosomes. After being stimulated by APMs, lysosome rupture leads to a loss of lysosomal acidic conditions and the inactivation of proteolytic enzymes, promoting an inflammatory response by activating the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. Moreover, APMs interfere with autophagosome production or block autophagic flux, resulting in autophagy dysfunction. Additionally, APMs disrupt the normal function of lysosomes in iron metabolism, leading to disruption on iron homeostasis. Therefore, understanding the impacts of APM exposure from the perspective of lysosomes will provide new insights into the detrimental consequences of air pollution.

Allium cepa tests: Exploring bleomycin induced cyto-genotoxicity and altered cell cycle kinetics in root tips meristematic cells.

Bleomycin, commonly employed in treating Hodgkin's lymphoma and testicular cancer, is associated with significant pulmonary toxicity. While various studies have assessed the toxic impact of chemotherapeutic agents on aquatic and terrestrial environments, limited data exist on bleomycin's effects, especially concerning higher plants. To address this gap, we utilized the Allium cepa assays, renowned for evaluating chemical and biochemical agents' toxic effects, to investigate bleomycin's impact on the terrestrial ecosystem. Our study aimed to assess bleomycin's cyto-genotoxic effects on A. cepa root tip cells at minimal concentrations (10-40 µg mL-1) and varied exposure durations (2, 4, 6, and 24 h). Analysis of nuclear and mitotic abnormalities in bleomycin-treated A. cepa root tip cells, alongside an acridine orange-ethidium bromide double staining assay, illuminated its influence on cell viability. Additionally, agarose gel electrophoresis determined the drug's potential for DNA degradation, unveiling the underlying mechanisms of cyto-genotoxicity. Results also demonstrated a decline in the mitotic index with increased bleomycin concentrations and exposure time, elevated frequencies of various cyto-genotoxic abnormalities, including sticky chromosomes, chromatid breaks, laggards, bridges, polar deviations, nuclear lesions, and hyperchromasia. The study indicated the potential risks of bleomycin even at low concentrations and brief exposures, highlighting its severe adverse effects on genetic material of plant, potentially contributing to cell death. Consequently, this investigation unveils bleomycin's cyto-genotoxic effects on higher plant system, underscoring its threat to terrestrial ecosystems, particularly upon chronic and unmonitored exposure.

Pulmonary evaluation of whole-body inhalation exposure of polycarbonate (PC) filament 3D printer emissions in rats.

During fused filament fabrication (FFF) 3D printing with polycarbonate (PC) filament, a release of ultrafine particles (UFPs) and volatile organic compounds (VOCs) occurs. This study aimed to determine PC filament printing emission-induced toxicity in rats via whole-body inhalation exposure. Male Sprague Dawley rats were exposed to a single concentration (0.529 mg/m3, 40 nm mean diameter) of the 3D PC filament emissions in a time-course via whole body inhalation for 1, 4, 8, 15, and 30 days (4 hr/day, 4 days/week), and sacrificed 24 hr after the last exposure. Following exposures, rats were assessed for pulmonary and systemic responses. To determine pulmonary injury, total protein and lactate dehydrogenase (LDH) activity, surfactant proteins A and D, total as well as lavage fluid differential cells in bronchoalveolar lavage fluid (BALF) were examined, as well as histopathological analysis of lung and nasal passages was performed. To determine systemic injury, hematological differentials, and blood biomarkers of muscle, metabolic, renal, and hepatic functions were also measured. Results showed that inhalation exposure induced no marked pulmonary or systemic toxicity in rats. In conclusion, inhalation exposure of rats to a low concentration of PC filament emissions produced no significant pulmonary or systemic toxicity.

Identification of toxicity-induced biomarkers in human non-immune airway cells exposed to respiratory sensitizers: A mechanistic approach.

Occupational asthma covers a group of work-related diseases whose clinical manifestations include airway hyperresponsiveness and airflow limitation. Although the chemical respiratory allergy (CRA) induced by Low Molecular Weight (LMW) sensitizers is a major concern, especially in terms of the regulatory framework, to date there are no methods available for preclinically addressing this toxicological outcome, as its mechanistic background is not fully understood at molecular or cellular levels. This paper proposes a mechanistic study applying New Approach Methodologies (NAM) of the pro-inflammatory and functional effects triggered by LMW respiratory allergens in different respiratory tract cell lines, including bronchial epithelial (BEAS-2B), lung fibroblast (MRC-5), and endothelial cells (EA.hy926), and an analysis of the capacity of such chemicals to interact with the mucin protein, to address certain toxicodynamic aspects of such compounds. The results showed that some of the sensitizers evaluated interact with mucin, the main protein mucus component, but the toxicant-mucin complex formation does not seem to be a common feature of different chemical classes of allergens. At a cellular level, sensitizers promoted an increase in IL-8, IL-6, and IL-1ß production in the evaluated cell types. It also impaired the MUC1 expression by bronchial cells and activated endothelial cells, thereby increasing the ICAM-I surface expression. Taken together, our results showed that these aforementioned cell types participate in the CRA Adverse Outcome Pathway and must be considered when developing preclinical testing strategies, particularly investigating danger signal production after exposure to LMW sensitizers in different tissue compartments.