Toxicology Mechanisms and Methods最新文献

{"title":"Transcriptomic profiling reveals crizotinib-induced hepatotoxicity through ROS-mediated activation of the JNK/NLRP3 pathway.","authors":"Min Li, Zhouli Yue, Menglin Wang, Yan Wang, Peng Xiao, Wei Yuan, Jiduo Shen, Yucheng Li","doi":"10.1080/15376516.2025.2536058","DOIUrl":"https://doi.org/10.1080/15376516.2025.2536058","url":null,"abstract":"<p><p>Crizotinib, a first-generation tyrosine kinase inhibitor, demonstrates excellent clinical efficacy in treating non-small cell lung cancer (NSCLC). However, its clinical application is often limited by severe hepatotoxicity, the underlying mechanisms of which remain poorly understood. This study aimed to investigate the molecular mechanisms of crizotinib-induced hepatotoxicity in mice using transcriptomic analysis. Male ICR mice were orally administered crizotinib at doses of 100, 200, and 300 mg/kg for 7 consecutive days. Hepatotoxicity was assessed by measuring serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, along with histopathological evaluation via hematoxylin and eosin (H&E) staining. Transcriptomic and bioinformatics analyses of liver tissues were conducted to identify potential toxicological pathways. Oxidative stress markers were quantified using biochemical assay kits. Hepatic macrophage activation was examined by F4/80 immunostaining, and protein expression levels were analyzed by western blotting. Crizotinib administration resulted in dose-dependent liver injury, as indicated by elevated serum ALT and AST levels, body weight loss, and histological abnormalities. Transcriptomic profiling revealed significant enrichment of oxidative stress-related pathways, with protein-protein interaction (PPI) analysis identifying Jun as a key hub gene. Crizotinib significantly increased hepatic reactive oxygen species (ROS), malondialdehyde (MDA), and oxidized glutathione (GSSG) levels, while reducing reduced glutathione (GSH) levels and the GSH/GSSG ratio. Additionally, crizotinib significantly upregulated Bax and downregulated Bcl-2 expression, promoted macrophage infiltration, and increased the expression of JNK and NLRP3 proteins. These findings suggest that crizotinib-induced hepatotoxicity may be mediated by ROS-induced activation of the JNK/NLRP3 signaling pathway, which subsequently promotes hepatic inflammation and apoptosis.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-12"},"PeriodicalIF":3.2,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ontogenetic development of metabolic and detoxification genes in <i>Seriola rivoliana</i> larvae.","authors":"Danitzia A Guerrero-Tortolero, Rafael Campos-Ramos","doi":"10.1080/15376516.2025.2534373","DOIUrl":"https://doi.org/10.1080/15376516.2025.2534373","url":null,"abstract":"<p><p>The early larval stages in marine organisms have evolved to possess a genomic response ensuring survival and protection against environmental stressors, defined as the 'chemical defensome'. The larval fish defensome consists of genes transcribed and upregulated after hatching to form detoxification proteins, catalyzing enzymes, transporters, transcription factors, and antioxidant proteins. Therefore, we aimed to analyze the timing of transcription and upregulation of metabolic, protective and detoxification genes during the ontogenetic development in <i>Seriola rivoliana</i> larvae up to the onset of exogenous feeding. Larvae samples from each experimental replicate were taken after hatching (day zero), day one (24 h post-hatching), day two (48 h post-hatching), day three (72 h post-hatching), and day four (96 h post-hatching). We used RNA-seq followed by gene annotation to identify these genes and to evaluate differential gene expression. From day one after hatching, results showed the upregulation of cytochrome P450 and other genes that coded for enzymes capable of bio-transform xenobiotic compounds such as reductases, hydrolases, transferases and dehydrogenases. Additionally, a set of genes of the superfamily of ATP-binding cassette transporters became upregulated for cholesterol homeostasis and many others involved in detoxification and multidrug resistance of xenobiotics. We also analyzed genes involved in stress-responses (transcription factors) and genes that code for antioxidants proteins. However, none of them showed differential expression. Our study suggests an orchestrated and organized ontogenetic sequential upregulation of the defensome as a natural process to adapt to the environment, the regulation process of macronutrients, and a defensive metabolic response in case of encountering harmful xenobiotic compounds or toxins in food and water at the onset of exogenous feeding, which contributes to the understanding of the chemical defensome in early marine larval development.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-15"},"PeriodicalIF":3.2,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>In vitro</i> effects of environmentally relevant concentrations of nonylphenol and selected pyrethroid metabolites on a mouse sertoli cell line (TM4).","authors":"Nthabiseng Kgabele Matjomane, Lisa Repsold, Sean Mark Patrick, Magdalena Catherina van Zijl, Michelle Helen Visagie, Natalie Hildegard Aneck-Hahn","doi":"10.1080/15376516.2025.2528100","DOIUrl":"10.1080/15376516.2025.2528100","url":null,"abstract":"<p><p>Advances in the chemical industry and increased environmental pollution have contributed to declining reproductive health. Many pollutants act as endocrine-disrupting chemicals (EDCs), with (anti-)estrogenic and (anti-)androgenic properties that disrupt hormonal balance and contribute to male reproductive dysfunction. Mouse Sertoli cells, which closely resemble human Sertoli cells, are targets for various environmental contaminants, making the cell line an ideal model for male reproductive toxicological studies. Sertoli cells (TM4) were exposed to environmentally relevant concentrations of EDCs, including cypermethrin, deltamethrin, rac-trans permethrinic acid, 3-phenoxybenzoic acid and <i>para</i>-nonylphenol (<i>p</i>-NP), for 24 h <i>in vitro.</i> Cytotoxicity was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, oxidative stress <i>via</i> an intracellular total reactive oxygen species (ROS) activity assay kit, and morphological changes <i>via</i> hematoxylin & eosin staining. The MTT assay revealed a moderate decrease (approximately 20% cell death) in cell viability. ROS levels were significantly higher in EDC-treated cells than in controls, with small effect sizes confirmed through Cohen's <i>d</i> analysis. Morphological changes, including membrane elongation, cytoplasmic vesicles, and reduced cell density, were most pronounced in <i>p-</i>NP-exposed cells. These findings suggest that exposure to pyrethroids and nonylphenol may induce toxicity in mouse Sertoli cells.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-10"},"PeriodicalIF":3.2,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144561256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Behavioral pharmacology and toxicology of dimethyl sulfoxide in <i>artemia</i> nauplii: vehicle or positive control?","authors":"Areeha Khalid, Matthew Pytynia, Sheila Cazares, Desiree K Batangan, Cassandra Repole, Andrew B Hawkey","doi":"10.1080/15376516.2025.2527160","DOIUrl":"10.1080/15376516.2025.2527160","url":null,"abstract":"<p><p>Dimethyl sulfoxide (DMSO) is a routinely used solvent in toxicology studies that are focused on toxicants with low natural solubility in water. However, prior research suggests that DMSO can alter neurological and behavioral outcomes under some circumstances, which could affect its suitability for neurotoxicology research. The current study evaluated the suitability of DMSO vehicles in an aquatic invertebrate model, <i>Artemia</i> nauplii. Subjects were exposed to solutions of 0.01-1% DMSO and assessed for mortality, motility, morphology, and recovery. In Experiment 1, 1-hr exposures significantly decreased swimming speed and increased rotation rates (0.01%, 1%) (slow, spiral swimming). In Experiment 2, 48-hr exposures suppressed swimming speed (0.1%, 1%), and path rotation (1%) (slower, non-spiral swimming), as well as body length (1%). In Experiment 3, following either 1-hr or 48-hr exposures to 1% DMSO, swimming speed and rotation rate persisted through 4-hr post-treatment, and recovered after a 24-hr washout period. Our results indicate that DMSO does affect motility and related behaviors in <i>Artemia</i> after 1- or 48-hr exposures, that these effects are reversible, and that progressive exposure to DMSO can alter the profile of effects. Consideration must be taken when determining what solvent to use when studying toxicants in aquatic species like <i>Artemia</i>.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-19"},"PeriodicalIF":3.2,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of polyethylene microplastics toxicity using Nrf2/ARE and MAPK/Nrf2 signaling pathways.","authors":"Mennatallah Mahmoud Ahmed Mohamed, Nada A Yousri, Noura Hassan Khamis, Shimaa Abdel Baset Abdel Hakim, Samar Hisham Elsayed, Elzahraa Ahmed Elrefaie Ali","doi":"10.1080/15376516.2025.2527154","DOIUrl":"10.1080/15376516.2025.2527154","url":null,"abstract":"<p><p>Microplastics (MPs) have emerged as a serious global environmental threat due to their resistance to degradation and persistence in ecosystems. Given their potential risks to human health, it is essential to thoroughly investigate the mechanisms of toxicity and associated health consequences. This study examined the toxicological and reproductive effects of varying doses of polyethylene microplastics (PE-MPs) in 120 male and female Sprague Dawley rats. A statistically significant, dose-dependent increase in malondialdehyde levels was observed, along with a reduction in catalase activity. Furthermore, alterations were detected in sexual hormone levels and disruptions were noted in both the Kelch-like ECH-associated protein 1 (Keap1)-Nrf2-ARE (antioxidant response element) and p38 MAPK-Nrf2 signaling pathways. PE-MP exposure also produced marked histopathological changes in the testes and ovaries. These findings indicate that reproductive toxicity from PE-MPs is associated with impairments in the Keap1-Nrf2-ARE and p38 MAPK-Nrf2 pathways. The results underscore the importance of limiting MP exposure to mitigate potential health hazards and provide new data on the potential mechanisms of toxicity of MPs.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-20"},"PeriodicalIF":3.2,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144529682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of simvastatin induced neurotoxicity on mitochondrial function in human neuronal cells.","authors":"Lauren Millichap, Nadia Turton, Razan Alomosh, Robert A Heaton, Amy Bateman, Nasser Al-Shanti, Adam P Lightfoot, Elisabetta Damiani, Fabio Marcheggiani, Patrick Orlando, Sonia Silvestri, Luca Tiano, Iain P Hargreaves","doi":"10.1080/15376516.2025.2471807","DOIUrl":"10.1080/15376516.2025.2471807","url":null,"abstract":"<p><p>3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR) inhibitors, commonly known as statins, are drugs frequently used in the treatment of hypercholesterolemia and hyperlipidemia. However, the current study has demonstrated that simvastatin induces neurotoxicity and is associated with cellular coenzyme Q₁₀ (CoQ₁₀) depletion. CoQ₁₀ has a significant role in the mitochondrial electron transport chain (ETC), in addition to being a fundamental lipid-soluble antioxidant. Depletion of CoQ₁₀ is frequently associated with impaired mitochondrial function and increased oxidative stress. The aim of this study was to investigate the potential mechanisms of simvastatin-induced neurotoxicity assessing mitochondrial function and evidence of oxidative stress in an <i>in vitro</i> SH-SY5Y human neuronal cell line. Fluorescence studies assessed <i>via</i> flow cytometry determined significant increases in intracellular and mitochondrial reactive oxygen species production following SH-SY5Y treatment with simvastatin compared to control cells. Additionally, spectrophotometric enzyme studies determined a significant (<i>p</i> < 0.0001) inhibition of ETC complex I and II-III activities which accompanied a significant decrease in neuronal CoQ₁₀ content (<i>p</i> < 0.005) and cell viability (<i>p</i> < 0.0001). The results of the present study have indicated evidence of mitochondrial dysfunction and increased oxidative stress, resulting in increased loss of neuronal viability following simvastatin treatment. Thus, these results demonstrate evidence of neurotoxicity associated with statin therapy.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"592-603"},"PeriodicalIF":3.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143543670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neodymium nitrate promotes the apoptosis of mouse liver cells via Bcl2l1/Caspase 3 pathway.","authors":"Jing Leng, Ning Wang, Xiu-Li Chang, Xiao-Peng Zhang, Jing Xu, Zheng-Li Yang, Ke-Lei Qian, Zhi-Qing Zheng, Gong-Hua Tao, Xu-Dong Jia, Ping Xiao, Xin-Yu Hong","doi":"10.1080/15376516.2025.2501253","DOIUrl":"10.1080/15376516.2025.2501253","url":null,"abstract":"<p><strong>Background: </strong>Neodymium, as a strategic rare earth element (REE), has demonstrated bioaccumulative potential and can permeate human systems through inhalation of airborne particulates, ingestion of contaminated food/water, and dermal absorption from soil matrices, ultimately eliciting multi-organ toxicological manifestations. However, the hepatotoxicological profile of neodymium species and their pathophysiological mechanisms remain inadequately characterized. Neodymium nitrate (Nd(NO₃)₃), the predominant water-soluble neodymium species, exhibits marked bioavailability with particular hepatic tropism.</p><p><strong>Objective: </strong>This study aims to investigate the effects of neodymium nitrate on apoptosis of mouse liver cells and its underlying molecular mechanisms.</p><p><strong>Results: </strong>Mouse liver cell line AML12 was treated with gradient concentrations of neodymium nitrate. The results showed that neodymium nitrate inhibited liver cell proliferation, induced apoptosis, and exhibited a dose-dependent relationship. Western blotting and quantitative real-time PCR (qRT-PCR) revealed that neodymium nitrate suppressed Bcl2l1 transcription and activated the proteolysis of Caspase 3. To further explore the molecular mechanism, Bcl2l1 protein was overexpressed in mouse liver cells. The findings indicated that overexpression of Bcl2l1 rescued neodymium nitrate-induced apoptotic phenotypes and attenuated Caspase 3 cleavage.</p><p><strong>Conclusion: </strong>The present data suggest that neodymium nitrate induces apoptosis of mouse liver cells through the Bcl2l1/Caspase 3 pathway. However, further studies are called for to substantiate this view, as the findings may provide critical mechanistic evidence for revising the toxicological risk assessment frameworks of rare earth elements.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"1-10"},"PeriodicalIF":3.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New mechanistic approach of TiCN film-coated NiTi substrate toxicity: impairment in mitochondrial electron transfer in diabetic rat tooth gum cells.","authors":"Abbas Razmi, Enayatollah Seydi, Behnaz Ashtari, Ali Neshasteh-Riz, Parvaneh Naserzadeh","doi":"10.1080/15376516.2025.2479000","DOIUrl":"10.1080/15376516.2025.2479000","url":null,"abstract":"<p><p>In recent years, researchers have focused on using new materials for screws in bone jaw tissue replacement. However, concerns regarding the cytotoxicity and biocompatibility of these materials for cells remain a subject of ongoing discussion. In this study, a novel implant for bone jaw tissue regeneration was fabricated by depositing the titanium carbo-nitride (TiCN) film on NiTi shape memory alloy substrate using the Cathodic Arc Physical Vapor Deposition (CAPVD) technique. Our study emphasized positive cellular responses of TiCN-coated NiTi substrate on diabetic rat tooth gum cells for 1, 15, and 30 days. Initially, the evaluation focused on the characterization and distribution of NiTi alloy in tissues. Then, the levels of factors such as components of White Blood Cells (WBC), ATP, oxidative stress parameters, cytochrome c release and damage to the lysosomal membrane were evaluated in all groups. The results indicated that in the group of diabetic rats with TiCN-coated NiTi substrate, the level of oxidative stress parameters decreased. In addition, the cell viability, glutathione (GSH) intracellular and ATP increased and the rate of cytochrome c release, and damage to the lysosome membrane decreased. It can be concluded that the TiCN-coated NiTi screw is a promising material for bone jaw tissue replacement in diabetic patients due to its low cytotoxicity.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"633-643"},"PeriodicalIF":3.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytotoxic potential of an indole-conjugated Oleanolic acid analogue: suppression of NSCLC proliferation through modulation of mitochondrial apoptotic dynamics.","authors":"Srividya Subramanian, Sankar Pajaniradje, Suhail Ahmad Bhat, Sathyapriya Chandramohan, Parthiban Anaikutti, Rukkumani Rajagopalan","doi":"10.1080/15376516.2025.2481915","DOIUrl":"10.1080/15376516.2025.2481915","url":null,"abstract":"<p><p>Pre-clinical toxicological investigations are pivotal in the development of safer and more efficacious chemotherapeutic agents. Oleanolic acid (OA), a naturally occurring pentacyclic triterpenoid, has demonstrated anticancer potential but is often limited by the toxic side effects of its derivatives. In the current study, we carried out the facile synthesis of a modified OA analogue, OD2, and studied its cytotoxicity and efficacy analysis across several cell lines. Mechanistic toxicology was explored through fluorescence-based assays. Annexin-V/Propidium Iodide (A-V/PI) staining and TUNEL assays were used to confirm apoptosis. OD2 exhibited dose-dependent cytotoxicity, with a pronounced effect on A549 lung cancer cells compared to other cancerous and non-cancerous cell lines. Apoptosis was found to be the predominant mode of cell death, evidenced by Fluorescence imaging analysis of chromatin condensation and mitochondrial dysfunction. This was further validated by an increase in Annexin-V-positive and TUNEL-positive cells in treated groups. OD2 activated the intrinsic mitochondrial apoptotic pathway as evidenced by increased Bax and decreased Bcl-2 protein abundance levels. While the current study showcases the therapeutic potential of the selective toxicological activity of OD2, future studies will focus on the deconvolution of its potential polypharmacological mode of action and decoding the basis of its selective action, so as to glean important lessons that can be applied in the development of chemotherapeutic agents with favorable toxicological profiles.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"668-681"},"PeriodicalIF":3.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the impact of ambient air PM_2.5 on multiple sclerosis: an experimental dive into neuroinflammation.","authors":"Shilan Mozaffari, Mohammad Sadegh Hassanvand, Maryam Baeeri, Mahdi Gholami, Zahra Bayrami, Masud Yunesian, Mohammad Ali Sahraian, Shekoufeh Nikfar, Mohammad Abdollahi","doi":"10.1080/15376516.2025.2468726","DOIUrl":"10.1080/15376516.2025.2468726","url":null,"abstract":"<p><p>There is mounting evidence about the connection between particulate matter (PM) and neuroinflammation. This study aimed to evaluate the toxicological effects of PM_2.5 associated with inflammatory factors in a mouse's multiple sclerosis (MS) model. Thirty C57BL/6 male mice were categorized into five groups: a group of healthy mice, a control cuprizone-induced MS group, and three MS-induced groups, intranasally exposed to three concentrations of ambient air PM_2.5 (5, 10, and 20 mg/mL) from Tehran in a phosphate-buffered saline (PBS) solution. All mice were investigated by motor function, molecular, and histopathological assays. Moreover, the chemical content of the collected PM_2.5 was assessed and reported. The cumulative exposure doses were equal to 0.025, 0.05, and 0.1 mg per gram of body weight of mice, which were approximately 3.52, 7.04, and 14.08 times higher than the human daily dose in Tehran. The PM_2.5-exposed groups showed a high inflammatory response characterized by a significant increase in the mRNA expression of tumor necrosis alpha (TNF-α), NLRP3, and interleukin 18 (IL-18). In addition, the PM_2.5-exposed groups exhibited a notably lower velocity level, total traveled distance (TD), and duration traveled in the central zone (DC) than the control group. The histopathological assays revealed significant pathological alterations and demyelination in the PM2.5-exposed groups compared to the control group. Identifying the risks and reducing the likelihood of exposure through preventive measures and regulations can result in financial savings and improve the quality of life for MS patients.</p>","PeriodicalId":23177,"journal":{"name":"Toxicology Mechanisms and Methods","volume":" ","pages":"581-591"},"PeriodicalIF":3.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}