Toxicology最新文献

{"title":"Food-borne polystyrene microplastic exposure exacerbates cognitive deficiency via enhanced neuronal synaptic damage and neuroinflammation in Alzheimer's disease","authors":"Chong Liu ,&nbsp;Yan Zhao ,&nbsp;Ji-ji Dao ,&nbsp;Yu-ke Ma ,&nbsp;Jie Liu ,&nbsp;Chen-meng Qiao ,&nbsp;Chun Cui ,&nbsp;Yan-qin Shen ,&nbsp;Shuang-xi Chen ,&nbsp;Li Yu ,&nbsp;Wei-jiang Zhao","doi":"10.1016/j.tox.2025.154371","DOIUrl":"10.1016/j.tox.2025.154371","url":null,"abstract":"<div><div>The impact of polystyrene microplastics (PS-MPs) on the nervous system has been documented, yet the potential role of PS-MPs exposure in exacerbating neuronal damage and neuroinflammation in Alzheimer's disease (AD) remains unclear. Our research demonstrated that oral exposure to PS-MPs caused hippocampal mitochondrial damage in APP/PS1 mice, reduced expression of hippocampal mitochondrial and synapse-associated proteins, inhibited ErbB4 signaling pathway, and damaged hippocampal neurons. Additionally, PS-MPs exposure induced overactivation of astrocytes and microglia with NLRP3 pathway activation, increased β-amyloid (Aβ) deposition, and ultimately worsened cognitive dysfunction in APP/PS1 mice. Subsequent in vitro findings showed that PS-MPs exacerbated hippocampal neuronal damage under Aβ pathology, suppressed ErbB4 signaling pathway, and disrupted mitochondrial and synaptic function. The compromised hippocampal neurons enhanced microglial NLRP3 pathway activation. These results suggest that exposure to PS-MPs induces hippocampal neuronal damage, impairs mitochondrial and synaptic function, and exacerbates neuroinflammation and cognitive deficits, ultimately contributing to AD progression. Collectively, these findings enhance our understanding of the mechanisms by which MPs expedite the progression and influence management of AD.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"520 ","pages":"Article 154371"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145757679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro and in vivo thyroid hormone system disruption by perfluorooctane sulfonate (PFOS) and tetrabromobisphenol A (TBBPA)","authors":"Mette Stub ,&nbsp;Lars Dahmen ,&nbsp;Agnieszka A. Niklas ,&nbsp;Karen Mandrup ,&nbsp;Carter Kuehn ,&nbsp;Selina Arnold ,&nbsp;Anna-Louise Liersch ,&nbsp;Jermaine Ford ,&nbsp;Mary Gilbert ,&nbsp;Kostja Renko ,&nbsp;Marta Axelstad ,&nbsp;Terje Svingen ,&nbsp;Louise Ramhøj","doi":"10.1016/j.tox.2025.154353","DOIUrl":"10.1016/j.tox.2025.154353","url":null,"abstract":"<div><div>Thyroid hormone (TH) system-disrupting chemicals can cause adverse effects, including neurodevelopmental deficits. While current <em>in vivo</em> test methods reliably detect disruptions from potent antithyroid drugs such as propylthiouracil (PTU) and methimazole (MMI) through thyroid gland histopathology, they may lack sensitivity for less potent chemicals or those acting through alternative mechanisms. A more systemic, mechanism-based approach may therefore be needed to identify TH system-disrupting capacity. Here, we assessed the effects of the environmental chemicals perfluorooctane sulfonate (PFOS) and tetrabromobisphenol A (TBBPA) on the TH system using <em>in vitro</em> and <em>in vivo</em> approaches. PFOS inhibited the TH transmembrane transporter monocarboxylate transporter 8 (MCT8) and the sodium-iodide symporter (NIS). TBBPA inhibited MCT8, the enzyme activity of all three iodothyronine deiodinases (DIO1/2/3), and thyroperoxidase (TPO). In time-mated rats, <em>in utero</em> and early postnatal exposure to PFOS (0.4 or 0.8 mg/kg bw/day) or TBBPA (250 or 500 mg/kg bw/day) reduced serum TH concentrations in dams and offspring, but neither chemical altered thyroid stimulating hormone (TSH) in offspring. We observed no, or only modest, effects on thyroid gland histology. Both chemicals altered TH metabolism by deiodinase and dehalogenase enzymes and reduced iodine content in the thyroid. In the fetal brain, PFOS increased T3, while TBBPA decreased T4 in the postnatal brain. These findings demonstrate distinct TH-disrupting profiles of PFOS and TBBPA, differing from classic antithyroid compounds PTU and MMI. Our results highlight the need for more comprehensive systems-approaches to capture TH disrupting chemicals acting through diverse mechanisms.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"520 ","pages":"Article 154353"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145597607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydramethylnon-induced autophagy and apoptosis in human bronchial epithelial cells by homeostatic changes","authors":"Yeon-Ho Kang ,&nbsp;Sou Hyun Kim ,&nbsp;Hye-Jin Jeong ,&nbsp;Ah-Yoon Song ,&nbsp;Hye-In Park ,&nbsp;Eun-Hye Kim ,&nbsp;Young-Suk Jung ,&nbsp;Yong Joo Park","doi":"10.1016/j.tox.2025.154338","DOIUrl":"10.1016/j.tox.2025.154338","url":null,"abstract":"<div><div>Household chemicals are commonly used products worldwide; however, their effects on human respiratory health are poorly understood. In this study, we aimed to investigate the effects of hydramethylnon (HDM), an insecticide frequently found in household products, on human bronchial epithelial cells (BEAS-2B) using <em>in vitro</em> experiments. The cells were exposed to varying concentrations of HDM (range, 1–4 µg/mL) for 24 h, followed by the evaluation of cell viability, apoptotic markers, metabolite levels, and antioxidant levels. The results showed that HDM exposure significantly increased oxidative stress by elevating the levels of reactive oxygen species, leading to the autophagosome accumulation and impaired autophagic flux (manifested by increased LC3B and p62 levels) and apoptosis (detected by increased cleaved caspase-3 and Bax/Bcl-2 levels and cytochrome c release). Flow cytometry confirmed that dose-dependent apoptotic cell death was further enhanced by chloroquine, an autophagy inhibitor. HDM exposure also resulted in a dose-dependent decrease in the messenger RNA levels of antioxidant enzymes, including catalase and glutathione peroxidase, and notable disruptions in sulfur-containing metabolites, including decreased levels of S-adenosylmethionine, S-adenosylhomocysteine, taurine, and glutathione. These metabolic perturbations were significantly aggravated by autophagy inhibition, suggesting autophagy-lysosome pathway plays a protective role against HDM-induced oxidative damage. These results suggest that HDM exposure poses substantial risks to human respiratory health through the oxidative stress-mediated disruption of antioxidant defense systems and metabolic pathways, ultimately impaired autophagic flux and mitochondria-mediated apoptosis in bronchial epithelial cells. This study highlights the need for improved safety guidelines and risk assessments of human inhalation exposure to household insecticides, particularly HDM.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"520 ","pages":"Article 154338"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitotoxic effects of the melanin-concentrating hormone receptor 1 (MCHr1) antagonist AZD1979 are influenced by mitochondrial DNA variation in HepG2 cybrids","authors":"Rebecca L. Jensen ,&nbsp;Robyn T. Kiy ,&nbsp;Carol E. Jolly ,&nbsp;Dominic P. Williams ,&nbsp;Amy E. Chadwick","doi":"10.1016/j.tox.2025.154365","DOIUrl":"10.1016/j.tox.2025.154365","url":null,"abstract":"<div><div>AZD1979 is a melanin-concentrating hormone receptor 1 (MCHr1) antagonist, which was developed for obesity treatment, but clinical development was halted due to unanticipated liver toxicity. Mitochondrial DNA (mtDNA) variation influences hepatic energy metabolism and may underlie individual susceptibility to drug-induced mitotoxicity. Transmitochondrial cybrids offer a model to assess the impact of mtDNA variation on drug response against a constant nuclear background. This study assessed the mitotoxic potential of AZD1979 in HepG2 wild-type (WT) cells and HepG2 transmitochondrial cybrids representing distinct mtDNA haplogroups from the H and J haplogroup lineages. A 2-hour acute metabolic switch assay was performed in HepG2 WT cells and transmitochondrial cybrids to identify mitochondrial toxicity, with confirmatory Seahorse extracellular flux analysis. AZD1979 was identified as a potent mitotoxicant in HepG2 WT cells, inducing mitochondrial dysfunction prior to cell death. AZD1979 caused reductions in basal respiration, ATP-linked respiration, and spare respiratory capacity, and inhibited complex I-driven respiration. Cybrids displayed haplogroup-specific differences in susceptibility. Haplogroup J2b1g showed the highest sensitivity, while J1c1e, despite lacking spare respiratory capacity, was less susceptible. These findings highlight the role of mtDNA in shaping individual responses to mitochondrial toxicants and that transmitochondrial cybrid models could support early assessment of mitochondrial liability.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"520 ","pages":"Article 154365"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145688126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dose-inverted neurotoxicity: La₂O₃ nanoparticles cause redox dysregulation at low concentrations but excitotoxic catastrophe at high doses","authors":"Nouf M. Alyami ,&nbsp;Rasha Alonaizan ,&nbsp;Hussah Alobaid ,&nbsp;Saleh Maodaa ,&nbsp;Norah S. Alothman ,&nbsp;Noura M. Alshiban ,&nbsp;Zainab A. Alnakhli ,&nbsp;Meshari M. Alyami ,&nbsp;Rafa Almeer","doi":"10.1016/j.tox.2025.154358","DOIUrl":"10.1016/j.tox.2025.154358","url":null,"abstract":"<div><div>This study investigated the effects of lanthanum oxide nanoparticles (La₂O₃ NPs) on cognitive and motor functions in female mice. We used behavioral tests, biochemical analysis, and tissue examination. Our findings indicate that neurotoxicity is dose-dependent, with distinct mechanisms at play. Low doses (60 mg/kg) caused severe oxidative stress, increasing a key damage marker (MDA) by 40–80 times and depleting antioxidants (glutathione) in the blood. These doses also led to the accumulation of pro-oxidant metals (Fe, Mn, Cu, Ti) and a reduction in brain calcium levels, as determined by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). At moderate doses, mice exhibited hyperactive movement but normal muscle strength, indicating a brain-specific effect. In contrast, high doses (300 mg/kg) triggered a different pattern of damage. This included a harmful calcium-potassium imbalance, disruption of key brain health signals (BDNF pathway), and widespread neuronal death. These changes are associated with significant cognitive deficits in avoidance learning and a complete lack of response to warning stimuli. Histopathological analysis revealed that neurotoxicity primarily affected motor coordination pathways, with degeneration observed in the cerebellum and medulla. We propose that La₂O₃ NPs release La³ ⁺ ions, which disrupt cellular calcium balance and produce harmful reactive oxygen species (ROS). This leads to two toxicity phases: at low doses, metal ions drive ROS generation, while at high doses, nanoparticle aggregation causes a catastrophic failure of ion regulation in neurons. These findings have important implications for understanding nanomaterial-induced neurodegeneration and creating protective strategies against La₂O₃ exposure.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"520 ","pages":"Article 154358"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145649339","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The combined exposure to AFB1 and DON induces the ferroptosis of porcine intestinal epithelial cells via down-regulating PI3K-AKT signal pathway","authors":"Wenshuo Zhao ,&nbsp;Qirui Yang ,&nbsp;Yuqi Song ,&nbsp;Yuhang Sun","doi":"10.1016/j.tox.2025.154343","DOIUrl":"10.1016/j.tox.2025.154343","url":null,"abstract":"<div><div>Aflatoxin B1 (AFB1) and deoxynivalenol (DON) are two highly hazardous mycotoxins often coexisting in feed, threating animal intestinal health. Ferroptosis, a regulated cell death linked to iron metabolism disorders, lipid peroxidation, and amino acid metabolism abnormalities, may involve in mycotoxins’ toxicity, but their interaction mechanism is unclear. This study used porcine intestinal epithelial cells (IPEC-J2) an <em>in vitro</em> model to explore ferroptosis mechanisms induced by AFB1 and DON alone or combined. The results showed that AFB1 and DON significantly reduced the viability of IPEC-J2 cells. Single and combined exposure to AFB1 and DON up-regulated the levels of MDA and ROS, while down-regulated the level of GSH. Meanwhile, they increased intracellular Fe^2 + content, accompanied by significantly down-regulated expressions of ferroptosis-related proteins including GPX4, SLC7A11 and FTH1, while markedly up-regulated the TFR1 protein level. Transmission electron microscopy (TEM) observation further confirmed that mitochondria suffered severe damage (shrinkage, cristae detachment and vacuolization). Mechanistically, single and combined exposure to AFB1 and DON down-regulated the protein levels of p-PI3K and p-AKT. Notably, the use of the PI3K activator 740Y-P significantly reversed aboved these changes. In addition, correlation analysis and molecular docking confirmed a strong positive correlation between PI3K/AKT signals and ferroptosis. In conclusion, single and combined exposure to AFB1 and DON induced IPEC-J2 ferroptosis by inhibiting PI3K-AKT, providing new insights for mycotoxin toxicity studies.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"520 ","pages":"Article 154343"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145565497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative assessment of endocrine disruption: From in vitro mechanisms to species extrapolation – Highlights of the German Pharma-Tox Summit 2025","authors":"Ute Haßmann ,&nbsp;Lisa Gölz ,&nbsp;René Geci ,&nbsp;Konstantinos Stefanidis ,&nbsp;Justin Lucky Brandt ,&nbsp;Eleanor North ,&nbsp;Katreece Feiertag ,&nbsp;Christel Renate Schopfer ,&nbsp;Sigrid Amann ,&nbsp;Stephanie Melching-Kollmuss ,&nbsp;Robert Landsiedel","doi":"10.1016/j.tox.2025.154370","DOIUrl":"10.1016/j.tox.2025.154370","url":null,"abstract":"<div><div>Endocrine-disrupting chemicals (EDCs) are a growing focus in human and environmental risk assessment, as reflected by the new EU CLP hazard classes for endocrine disruptors. Within this context, the symposium “Cross-Species Extrapolation in Endocrine Disruption Assessments” was held at the 10th German Pharm-Tox Summit (GPTS) 2025 in Hannover (March 11–13), which formed part of the 91st annual meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT). The symposium assembled diverse lines of research addressing endocrine disruption from complementary angles. Contributions ranged from advanced experimental model systems, such as refined zebrafish embryo assays for thyroid hormone disruption, to high-throughput in silico and in vitro–based kinetic modelling frameworks that support quantitative in vitro to in vivo extrapolation and AOP-informed risk assessment. Clinical and translational perspectives were added by targeted LC–MS/MS profiling of steroid conjugates as biomarkers for adrenal tumours. Further talks expanded the mechanistic toolbox for thyroid disruption, including enzyme- and protein-binding–based in vitro assays, and highlighted metabolic endocrine disruptors that act beyond the EATS (estrogen, androgen, thyroid and steroidogenesis) pathways. A regulatory-oriented analysis of thyroid-related modes of action across vertebrate taxa underscored the importance of clearly defining domains of applicability for cross-species extrapolation. At the same time, the discussions revealed critical gaps, including still limited taxonomic applicability domains, incomplete regulatory coverage beyond established endocrine pathways and limited transparency in predictive tools. Together, these contributions illustrate how integrated experimental, computational and regulatory science can advance mechanism-based, animal-reduced assessment of endocrine disruptors.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"520 ","pages":"Article 154370"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145752286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chlorocholine chloride delays progenitor Leydig cell differentiation via PI3K/AKT pathway activation in rats","authors":"Haoran Zhang ,&nbsp;Yijia Li ,&nbsp;Xiaoxia Wang ,&nbsp;Chenping Kang ,&nbsp;Qiong Zhang ,&nbsp;Defeng Liu ,&nbsp;Jiaming Mao ,&nbsp;Qianqian Xiao ,&nbsp;Weidong Hao","doi":"10.1016/j.tox.2025.154367","DOIUrl":"10.1016/j.tox.2025.154367","url":null,"abstract":"<div><div>Chlorocholine chloride (CCC) is a commonly used plant growth regulator. It was shown that CCC exposure could lead to decreased testosterone biosynthesis, delayed puberty onset, and damaged spermatogenesis in pubertal rodents, but the underlying mechanism is still not well understood. The testosterone level is determined not only by the functional activity of Leydig cell but also by its number and maturational status. To identify the critical developmental stage at which CCC impairs Leydig cell maturation and elucidate its underlying mechanisms, pubertal rats were exposed to 0, 75, 137.5, and 200 mg/kg bw/day CCC from PND14 (progenitor Leydig cells, PLCs) to PND28 (immature Leydig cells, ILCs) and from PND28 to PND56 (adult Leydig cells, ALCs) respectively. The results showed that, for exposure from PLCs stage, CCC exposure at 137.5 and 200 mg/kg bw/day led to histopathological changes of rat testes and impaired Leydig cell lineage specification in rats. CCC exposure at 200 mg/kg bw/day significantly decreased the mRNA expression of <em>Star</em>, <em>Lhcgr</em>, <em>Cyp17a1</em>, and <em>Hsd17b3</em>. Hormonal measurement and proteomic analysis revealed that both the disruption of the hypothalamic-pituitary-testis axis and the aberrant activation of the PI3K/AKT signaling pathway contribute to the impairment of Leydig cell lineage specification. For exposure from ILCs stage, Leydig cell development was not affected, but serum and testicular testosterone levels decreased resulting from the down-regulation of StAR, CYP11A1, and HSD3B1. In conclusion, our study found that CCC exposure could delay the development process of rat Leydig cells by disruption of Leydig cell differentiation during early developmental stage, which might lead to decreased testosterone level.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"520 ","pages":"Article 154367"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145744633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term low-dose exposure to polystyrene nanoplastics induces morphological and transcriptional reprogramming to enhance metastatic potential of colorectal cancer cells","authors":"Yeongjae Kim ,&nbsp;Seon Yeong Park ,&nbsp;Ahyoung Jo ,&nbsp;Soyul Ahn ,&nbsp;Jisu Kwon ,&nbsp;Eui-Man Jung ,&nbsp;Hyung-Sik Kim ,&nbsp;Sanghwa Jeong ,&nbsp;Kyoung Eun Lee ,&nbsp;Chang-Kyu Oh ,&nbsp;Yun Hak Kim ,&nbsp;Jung-Min Oh","doi":"10.1016/j.tox.2025.154356","DOIUrl":"10.1016/j.tox.2025.154356","url":null,"abstract":"<div><div>Despite global efforts to reduce plastic consumption, its usage continues to rise, leading to increased environmental contamination and heightened concerns regarding the potential health impacts of nanoplastics. Owing to their prolonged residence time in the intestine, nanoplastics contribute to prolonged exposure and absorption by intestinal epithelial cells. In this study, we examined the effects of polystyrene micro- and nanoplastics of varying sizes (20 nm–1000 nm) on colorectal cancer cells (HCT116) through a series of in vitro experiments, including cell viability assays, morphological assessments, and transcriptomic profiling. Notably, long-term exposure of HCT116 cells to small-sized (20 nm) nanoplastics at a low-dose, one that does not cause acute toxicity, led to significant morphological changes and gene expression alterations. These modifications included the upregulation of markers associated with migration, cancer stem cell (CSC) properties, and epithelial–mesenchymal transition (EMT). The enhanced expression of migration markers correlated with increased cell motility. Consistent with these in vitro findings, zebrafish models demonstrated accelerated metastasis of colorectal cancer cells following nanoplastic exposure. Collectively, these results suggest that nanoplastics may contribute to colorectal cancer progression, providing new insights into the molecular mechanisms underlying this process.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"520 ","pages":"Article 154356"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145606161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological responses of human tracheobronchial mucociliary pseudo-epithelium repeatedly exposed at the air-liquid interface to PM10 indoor particles","authors":"Carine El Hajjar ,&nbsp;Ivannah Pottier ,&nbsp;Marie Lelong ,&nbsp;Valérie Lecureur ,&nbsp;Véronique André","doi":"10.1016/j.tox.2025.154369","DOIUrl":"10.1016/j.tox.2025.154369","url":null,"abstract":"<div><div>The PM₁₀ fraction of representative indoor pollution (SRM® 2585) was repeatedly nebulized (1 and 6 μg/cm²/day) on functional mucociliary pseudo-epithelia (NHBE cells differentiated at the Air Liquide Interface, ALI). Four consecutive daily exposures have been performed and the biomarkers were analyzed on day 4, 8 and 11. Exposures at the lower dose induced at day 4 a significant increase in cellular ROS and modulations of the expression of few genes associated with genotoxicity and oxidative stress. IL-6 expression was strongly upregulated accompanied by a delayed increased secretion in the basal medium, whereas IL-8 expression was downregulated. At the highest dose, a weak and transient decrease in epithelial cohesion was observed, as well as a potential alteration of the cilia. The mucus secretion tended to increase whereas expression of MUC5AC and MUC5B was downregulated. Co-exposure to macrophage mediators (produced by pre-exposure of human macrophages to the PM_2.5 fraction of SRM® 2585) induced significant overexpression of MUC5AC, IL-6 and IL-8 in the pseudo-epithelium. Three genes involved in oxidative processes, distinct from those highlighted with PM₁₀ alone, were modulated. Despite repeated exposures, the magnitude of the mucociliary pseudo-epithelial responses remained low overall. Trapping of PM₁₀ in the mucus associated with efficient ciliary beating contributed to limit cellular responses. Thus, this physiological process must be considered for realistic <em>in vitro</em> toxicity assessments. Co-exposure protocol allowed to integrate the role of the innate immune system into the overall response of the lung tissue.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"520 ","pages":"Article 154369"},"PeriodicalIF":4.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145747530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}