Particle and Fibre Toxicology最新文献

{"title":"Inhalation toxicity, pulmonary clearance, and biotransformation of ferric oxide nanoparticles in rats.","authors":"Songyeon Kim, Jiyoung Jeong, Seunghan Lee, Jaehyuck Sung, Kyung Seuk Song, Wan-Seob Cho","doi":"10.1186/s12989-026-00659-8","DOIUrl":"10.1186/s12989-026-00659-8","url":null,"abstract":"<p><strong>Background: </strong>Ferric oxide (Fe₂O₃) nanoparticles are widely used in industrial and biomedical applications, raising concerns regarding inhalation exposure, particularly in occupational settings. Although the inhalation toxicity of magnetite (Fe₃O₄) was reported, no studies have addressed the pulmonary clearance, biotransformation, or systemic distribution of Fe₂O₃ nanoparticles. In this study, male rats were exposed nose-only to aerosols of γ-Fe₂O₃ nanoparticles at concentrations of 0.56, 1.63, and 4.92 mg/m³ for 6 h/day, 5 d/week, over 28 d, followed by recovery periods of 7 and 28 d. Particulate and ionic iron were separately collected via proteinase K digestion and quantitatively and qualitatively evaluated using elemental quantification and electron microscopy.</p><p><strong>Results: </strong>The toxicity study showed no treatment-related effects, including clinical signs, body weight, hematology, serum biochemistry, or histopathology. Lung burden analysis revealed a clearance half-life of 3.6-3.91 d, with ~ 25% of the initially deposited iron (Fe) retained after 28 d of recovery. At this time point, the retained Fe persisted as particulates biotransformed into fragments of a few nanometers, with a smaller portion present as ionic Fe. The extrapulmonary distribution showed ionic Fe in the liver and spleen, whereas particulate Fe was confined to the lung-associated lymph nodes. This study provides the first inhalation toxicity and biodistribution data for γ-Fe₂O₃ nanoparticles obtained under regulatory testing conditions, demonstrating subacute inhalation toxicity outcomes and revealing their persistence in the lungs without systemic translocation of intact particles. This study is the first subacute inhalation toxicity study conducted under regulatory testing conditions and includes a comprehensive in vivo biokinetic and biotransformation analysis, revealing the long pulmonary biopersistence of γ-Fe₂O₃ nanoparticles and the absence of systemic translocation of intact particles, with only limited extrapulmonary distribution of their ionic biotransformation products.</p><p><strong>Conclusions: </strong>Although γ-Fe₂O₃ nanoparticles persist in the lungs without overt toxicity, their prolonged retention and biotransformation into smaller particles may ultimately lead to overload-driven oxidative stress and chronic pulmonary effects.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":"3"},"PeriodicalIF":10.6,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12829270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145966795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Organ and tissue accumulation of titanium dioxide after acute, subacute, subchronic, and chronic oral exposure in mice and rats: a systematic review.","authors":"Vida Mohammadparast, Jangrez Khan, Penelope Truman, Nicholas D Kim, Marlena C Kruger, Collette Bromhead, Beth L Mallard","doi":"10.1186/s12989-025-00651-8","DOIUrl":"10.1186/s12989-025-00651-8","url":null,"abstract":"<p><strong>Background: </strong>Titanium dioxide (TiO₂) is a compound that is often used as a white pigment. Commercial TiO₂, such as the food additive E171, contains a mix of particle sizes, including a fraction in the nanoscale range (< 100 nm). It is an ingredient in everyday products such as toothpaste, dietary supplements, and pharmaceuticals. Although the oral and gastrointestinal (GIT) tracts are the initial sites of exposure, in vivo studies have shown that TiO₂ can cross the intestinal epithelium, enter systemic circulation, and accumulate in vital organs, where elimination is slow. This accumulation has been associated with oxidative stress, inflammation, cytotoxicity, and altered cellular function.</p><p><strong>Main body: </strong>This systematic review assesses titanium (Ti) accumulation in vital organs of rats and mice following oral TiO₂ exposure, focusing on dose- and time-dependent patterns across acute, subacute, subchronic, and chronic durations. Following PRISMA guidelines, 3,012 records were identified and screened by title and abstract, with 54 studies meeting predefined inclusion criteria. The findings reveal that acute oral exposure to TiO₂ consistently results in minimal titanium accumulation across all major organs, indicating limited gastrointestinal absorption and rapid excretion. In contrast, subacute and subchronic exposures lead to significant, dose-dependent titanium accumulation, especially in the liver, spleen, kidneys, gastrointestinal tract, and brain. Chronic exposure studies, though fewer, indicate persistent Ti presence, especially in the liver, kidneys, and colon. Ti was also found in the brain, pancreas, and reproductive tissues, with histopathological changes indicating broader systemic effects. A few studies reported negligible accumulation even at high doses.</p><p><strong>Conclusion: </strong>This review highlights the organ-specific and exposure-dependent biodistribution of titanium following oral TiO₂ intake in rodents. The evidence emphasizes the need for standardized reporting and experimental methodologies to improve data comparability across studies. Importantly, it underscores significant gaps in our understanding of chronic and low-dose exposures, conditions more reflective of real-world human scenarios, warranting further investigation to better assess long-term health risks.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"23 1","pages":"1"},"PeriodicalIF":10.6,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12781841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into the causal role of diesel exhaust particles in ventricular arrhythmogenesis: protective effects of antioxidant cerium oxide nanoparticles.","authors":"Freddy G Ganse, Lena M Ernst, Cristina Rodríguez, Marisol Ruiz-Meana, Javier Inserte, José Martínez-González, Ana M Briones, Ana Belén García-Redondo, Marta Consegal, Elisabet Miró-Casas, Laia Yáñez-Bisbe, Aitor Pomposo, Marta Prades-Martínez, Ignacio Ferreira-González, Victor Puntes, Begoña Benito, Antonio Rodríguez-Sinovas","doi":"10.1186/s12989-025-00649-2","DOIUrl":"10.1186/s12989-025-00649-2","url":null,"abstract":"<p><strong>Background: </strong>Epidemiological studies suggest an association between air pollution and ventricular arrhythmias, with reactive oxygen species (ROS) playing a crucial role. However, the causal relationship and long-term effects remain uncertain, and the effectiveness of interventions aimed at reducing ROS requires further investigation. Here we aimed to evaluate the effects of a 3-weeks exposure to diesel exhaust particles (DEPs) on ventricular arrhythmogenesis, explore the underlying mechanisms, and assess the potential of cerium oxide nanoparticles (CeO₂NP) as a ROS-detoxifying intervention.</p><p><strong>Results: </strong>Sprague-Dawley rats underwent intratracheal instillation of saline without or with DEPs (7.5 g/Kg for 1-3 weeks). Ventricular arrhythmia inducibility was then assessed in isolated hearts using a protocol of programmed electrical stimulation. Cardiac hypertrophy, collagen content, inflammation and oxidative stress were analyzed using histology, Western blot, RT-qPCR, and measurement of malondialdehyde content. The potential protective effects of CeO₂NP (0.5 mg/Kg/week, i.p.) were also tested. DEP exposure for 3 weeks increased the incidence and duration of sustained ventricular tachyarrhythmias (VTs), a finding that correlated with a moderate increase in interstitial collagen (from 3.11 ± 0.12% in controls to 4.80 ± 0.21% in DEP-exposed rats, p < 0.001), and an early upregulation in the expression of collagen and other fibrotic and inflammatory markers. These effects associated with prolonged QRS complex and enhanced malondialdehyde content (356.7 ± 21.2 vs. 455.3 ± 17.2 μmol/g tissue, p = 0.0066) after 3 weeks. CeO₂NP treatment reduced oxidative stress and myocardial fibrosis, reversed electrocardiographic changes and attenuated DEP-induced pro-arrhythmic effects.</p><p><strong>Conclusions: </strong>DEP exposure increases the incidence and duration of sustained VTs, collagen deposition and oxidative stress in rats. Treatment with CeO₂NP attenuate these effects, arising as a potential novel strategy to mitigate the deleterious effects of air pollution.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"22 1","pages":"36"},"PeriodicalIF":10.6,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12739854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145828251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of surface functional group modification on cellular internalization and cytotoxicity of silica nanoparticles.","authors":"Sandra Vranic, Eri Watanabe, Kyoka Yamazaki, Takatsugu Wakahara, Kayoko Miyakawa, Sakie Takeuchi, Yurika Osada, Sahoko Ichihara, Wenting Wu, Cai Zong, Toshihiro Sakurai, Akira Sato, Yasushi Hara, Akihiko Ikegami, Yuya Terashima, Kouji Matsushima, Toshihiro Suzuki, Ryo Abe, Sonja Boland, Lang Tran, Gaku Ichihara","doi":"10.1186/s12989-025-00653-6","DOIUrl":"10.1186/s12989-025-00653-6","url":null,"abstract":"<p><strong>Background: </strong>Silica nanoparticles (SiO₂NPs) are widely used in industrial products. Surface modification of SiO₂NPs is one of the promising strategies to develop safer nanomaterials by design. The present study was designed to determine the effects of amino or carboxyl functionalization of rhodamine-labeled SiO₂NPs on cellular uptake and cytotoxicity.</p><p><strong>Methods: </strong>In the in vivo arm of the study, male mice were randomly divided into seven groups (n = 6, each) and exposed to either amino (NH₂)- or carboxyl (COOH)-functionalized, or non-functionalized (OH)-rhodamine-labeled SiO₂NPs at 2 or 10 mg/kg bw, or endotoxin-free water as a control, by pharyngeal aspiration. At 24 h after administration, the mice were euthanized and bronchoalveolar lavage fluid (BALF) was collected for differential cell count and assessment of silica nanoparticle uptake using confocal microscopy. In the in vitro arm of the study, murine RAW264.7 macrophages were exposed to NH₂-or COOH-functionalized or OH- rhodamine-labeled SiO₂NPs. Nonspecific caspase inhibitor, necroptosis inhibitor, pyroptosis inhibitor and autophagy inhibitor were used to determine the roles of cell death signaling in cytotoxicity.</p><p><strong>Results: </strong>The in vivo studies demonstrated significant increase in lung weight at 2 and 10 mg/kg bw by OH-SiO₂NPs but not the other two SiO₂NPs. At 10 mg/kg bw, COOH-SiO2NPs induced a significant increase in BALF macrophages, whereas OH- SiO₂NPs significantly decreased macrophages. OH-SiO₂NPs at 2 mg/kg bw and NH₂- and COOH-SiO₂NPs at 10 mg/kg bw significantly increased BALF neutrophiles. The in vitro studies showed greater NH₂-SiO₂NPs internalization into RAW264.7 macrophages than OH-SiO₂NPs, while OH-SiO₂NPs induced cytotoxicity and upregulation of IL-1β and TNF-α to greater extent than the other two types. Co-treatment with pan-caspase inhibitor and necroptosis inhibitor attenuated (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) cytotoxicity of OH-SiO₂NPs.</p><p><strong>Conclusion: </strong>NH₂- or COOH-functionalization reduced the harmful changes observed with OH- SiO₂NPs, which included increase in lung weight and BALF neutrophils at low dose in mice as well as decrease in cell viability and upregulation of proinflammatory cytokines in RAW264.7 macrophages. The results suggested that OH-SiO₂NPs-induced cytotoxicity against macrophages was mediated at least in part through apoptotic/necroptotic signaling but was not related to internalization of particles. The results imply possible development of safer silica nanoparticles by amino- or carboxyl-functionalization of their silanols.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":""},"PeriodicalIF":10.6,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12950232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-ambient PM_2.5 exposure disrupts hematopoietic homeostasis via HIF-1α-driven myeloid skewing and promotes organ inflammation.","authors":"Hongyan Yu, Yidi Chen, Yuanyuan Wang, Min Li, Gang Tang, Rong Zhang, Guangbo Qu, Xiaoting Jin, Yuxin Zheng, Guibin Jiang","doi":"10.1186/s12989-025-00654-5","DOIUrl":"10.1186/s12989-025-00654-5","url":null,"abstract":"<p><p>Environmental pollutants like PM_2.5 threaten hematopoietic homeostasis, yet how real-world exposure disrupts blood cell production, especially locally in the lung and systemically in the bone marrow (BM), remains poorly understood. Previous studies often used artificial particles or lacked mechanistic insights into systemic effects. Hypoxia-inducible factor-1alpha (HIF-1α) is essential for hematopoietic stem cell (HSC) maintenance. Herein, we utilized a real-ambient PM_2.5 exposure system and conducted a detailed characterization of hematopoietic and downstream immune cell populations in mice with myeloid lineage-specific knockout of HIF-1α (mHIF-1α^-/-) and their wild-type littermate controls. Our findings demonstrate that real-ambient PM_2.5 exposure induces a HIF-1α-dependent myeloid-biased hematopoiesis within both the lung and BM. This bias results in an accumulation of mature myeloid cells, particularly neutrophils and macrophages, in peripheral organs such as the liver and spleen. Critically, this cellular redistribution precipitates inflammatory injury in a HIF-1α-dependent manner. These results provide novel insights into how environmental contaminants, exemplified by PM_2.5, perturb hematopoiesis, highlighting the critical role of HIF-1α in mediating lineage-specific hematopoietic responses and subsequent inflammatory sequelae.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":"35"},"PeriodicalIF":10.6,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12709752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145763482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep disruption from inhalation of biomass smoke: a basis for coincident hypertension?","authors":"K M Rentschler, W Kyle Martin, W Oshiro, M C Schladweiler, T W Jackson, W E Cascio, U P Kodavanti, P A Evansky, C Lambright, R Strader, J Conley, W Williams, D Freeborn, C N Miller, R Grindstaff, M Monsees, A A Lewis, D W Herr, P R S Kodavanti, M S Hazari, A K Farraj","doi":"10.1186/s12989-025-00650-9","DOIUrl":"10.1186/s12989-025-00650-9","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"22 1","pages":"34"},"PeriodicalIF":10.6,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12696922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhalation toxicity of arsenic-containing mine dust in an air-liquid interface bronchial epithelial model.","authors":"Xiaoli Ji, Yanping Li, Shuyi Gu, Zhen Min, Daoyuan Sun, Ziren Zhang, Wenkang Jiang, Jingbo Zhang","doi":"10.1186/s12989-025-00644-7","DOIUrl":"10.1186/s12989-025-00644-7","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"22 1","pages":"33"},"PeriodicalIF":10.6,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12659116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145637475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fiber length and shape-dependent differences in hepatic nanomaterial localization in mice following pulmonary exposure.","authors":"Mathilde Sundberg, Trine Berthing, Pernille Høgh Danielsen, Alicja Mortensen, Józef Szarek, Christelle N Prinz, Pernille Tveden-Nyborg, Ulla Vogel","doi":"10.1186/s12989-025-00652-7","DOIUrl":"10.1186/s12989-025-00652-7","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>These findings demonstrate that the intrahepatic localization of nanomaterials is strongly influenced by fiber shape and dimensions.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":" ","pages":"37"},"PeriodicalIF":10.6,"publicationDate":"2025-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12751881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145582405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of protease-activated receptor-2 attenuates multi-walled carbon nanotube exacerbation of allergic lung disease in mice.","authors":"Logan J Tisch, Ryan D Bartone, Silvio Antoniak, James C Bonner","doi":"10.1186/s12989-025-00648-3","DOIUrl":"10.1186/s12989-025-00648-3","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"22 1","pages":"32"},"PeriodicalIF":10.6,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12628615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145550241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renal transcriptome-wide analyses in association with kidney black carbon load.","authors":"Leen Rasking, Jasper Callemeyn, Congrong Wang, Rossella Alfano, Michelle Plusquin, Maarten Naesens, Tim S Nawrot, Katrien De Vusser","doi":"10.1186/s12989-025-00646-5","DOIUrl":"10.1186/s12989-025-00646-5","url":null,"abstract":"<p><strong>Rationale and objective: </strong>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.</p><p><strong>Study design: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":19847,"journal":{"name":"Particle and Fibre Toxicology","volume":"22 1","pages":"31"},"PeriodicalIF":10.6,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12625452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145550321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}