Toxicology最新文献

{"title":"Reflections on the NIEHS Virtual Consortium funding mechanism (ViCTER) and what it has taught us about the future of transdisciplinary science","authors":"Almudena Veiga-Lopez ,&nbsp;Hanna E. Stevens ,&nbsp;Matthew Rand ,&nbsp;Ronald Tjalkens ,&nbsp;Birgit Claus Henn ,&nbsp;Carmen J. Marsit ,&nbsp;Alison I. Bernstein ,&nbsp;Matthew R. Bonner ,&nbsp;Hanne M. Hoffmann ,&nbsp;Jaymie R. Meliker","doi":"10.1016/j.tox.2025.154283","DOIUrl":"10.1016/j.tox.2025.154283","url":null,"abstract":"<div><div>In environmental health science, collaboration across disciplines is often encouraged but rarely specifically solicited through funding mechanisms. The United States National Institute of Environmental Health Sciences (NIEHS) Virtual Consortium for Translational/Transdisciplinary Environmental Research (ViCTER) program fostered and promoted early-stage transdisciplinary collaborations among basic, clinical, and population-based researchers in the environmental health field. ViCTER awards are typically three-year R01 grants that include at least one NIEHS-funded PI and engage partners from distinct disciplines or institutions. By design, ViCTER created space for scientifically diverse research teams, including epidemiologists, clinicians, toxicologists, molecular biologists, often across multiple institutions, to work side-by-side, not sequentially, to address complex environmental challenges. This commentary reflects on how ViCTER catalyzed scientific advances, transformed careers, and created a model for the future of translational environmental health research.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"518 ","pages":"Article 154283"},"PeriodicalIF":4.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092435","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":"Hexafluoropropylene oxide homologues, the novel alternatives to PFOA, induce mitochondrial dysfunction and cytotoxicity in Leydig cells through disrupting SIRT1/PGC-1α signaling pathway","authors":"Mei-Ling Le ,&nbsp;Jia-Yu Xue ,&nbsp;Li-Hai Wu ,&nbsp;Xin-Yuan Zhao ,&nbsp;Jing Ding ,&nbsp;Yang-Yang Yuan ,&nbsp;Yi-Qi Wan ,&nbsp;Da-Lei Zhang","doi":"10.1016/j.tox.2025.154282","DOIUrl":"10.1016/j.tox.2025.154282","url":null,"abstract":"<div><div>Hexafluoropropylene oxide (HFPO) homologues (HFPOs), specifically HFPO-dimeric acid (DA), HFPO-trimeric acid (TA) and HFPO-tetrameric acid (TeA), have emerged as industrial replacements for phased-out perfluorooctanoic acid (PFOA), garnering considerable attention due to their environmental ubiquity and bioaccumulation potential. Nevertheless, the reproductive toxicity of HFPOs remains incompletely characterized, particularly regarding their endocrine-disrupting effect and the underlying mechanisms involving Leydig cell dysfunction. In this study, we investigated the cytotoxic influences of HFPOs on TM3 Leydig cells, focusing on mitochondrial function and dynamics, oxidative stress, and apoptosis. Our findings demonstrated that exposure to HFPOs significantly compromised mitochondrial function and fusion-fission dynamics by disrupting the SIRT1/PGC1α signaling pathway. The mitochondrial dysfunction further triggered excessive ROS production and apoptosis, ultimately impairing TM3 Leydig cell viability and testosterone secretion. However, supplementation with the SIRT1 agonist SRT1720 relieved the inhibitory effect of HFPOs on SIRT1/PGC1α signaling pathway and reversed the expression of apoptosis-associated proteins (BAX/BCL2), oxidative stress-associated proteins (SOD1/SOD2), as well as proteins associated with mitochondrial fusion (MFN2/OPA1) and fission (DRP1/FIS1). These results elucidated the involvement of the SIRT1/PGC1α pathway in mediating the cytotoxicity of HFPOs. Notably, the activation of SIRT1 mitigated HFPO-induced toxicity in the TM3 cells, highlighting its potential in safeguarding testicular cells from the damage caused by HFPOs exposure.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"518 ","pages":"Article 154282"},"PeriodicalIF":4.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145092469","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":"Perinatal neurodevelopmental effects of endocrine disruptors: Insights from metabolome mapping in the rat hippocampus","authors":"Sara Evangelista ,&nbsp;Walter Lichtensteiger ,&nbsp;Margret Schlumpf ,&nbsp;Lisa Rancan ,&nbsp;Sergio D. Paredes ,&nbsp;Beatriz Linillos-Pradillo ,&nbsp;Marja H. Lamoree ,&nbsp;Pim E.G. Leonards","doi":"10.1016/j.tox.2025.154281","DOIUrl":"10.1016/j.tox.2025.154281","url":null,"abstract":"<div><div>Metabolism is critical for neurodevelopment, yet the mechanisms by which endocrine-disrupting chemicals (EDCs) contribute to neurodevelopmental disorders remain poorly defined. Using a rat model, we investigated hippocampal metabolomic responses at postnatal day 6 following maternal exposure to six structurally diverse EDCs (bisphenol F, permethrin, butyl benzyl phthalate, triphenyl phosphate, perfluorooctane sulfonic acid, and DINCH) from pre-mating through lactation. Targeted steroid, thyroid, and neurosteroid hormones, neurotransmitters, and untargeted lipidomics were profiled to map disrupted pathways. The analysis revealed sex-specific, chemical-specific, and shared metabolic signatures of developmental neurotoxicity. Key affected endpoints across chemicals included corticosterone, pregnenolone sulfate, and N-acylethanolamine lipids, confirming hormonal disruption while uncovering novel non-EATS (estrogen, androgen, thyroid, and steroidogenesis) pathways and mechanisms of action. These findings provide new insights into EDC-mediated disruption of hippocampal development and identify potential molecular biomarkers that may support future mechanistic research and chemical risk assessment.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"518 ","pages":"Article 154281"},"PeriodicalIF":4.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087409","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":"Mechanistic toxicity profiling of chemicals: a comparative study in 2D and 3D HepaRG models using High-Content Analysis.","authors":"Mariam Saleh, Kevin Hogeveen, Valérie Fessard, Ludovic Le Hégarat","doi":"10.1016/j.tox.2025.154280","DOIUrl":"https://doi.org/10.1016/j.tox.2025.154280","url":null,"abstract":"<p><p>Humans and the environment are exposed to a diverse range of chemicals, many of which are introduced through the human activities. This growing chemical burden has given rise to concerns related to their potential adverse effects. Traditionally, chemical toxicity evaluation has relied on animal tests that are time consuming, expensive, pose ethical concerns, and may not be directly extrapolated to humans. This highlights the urgent need to develop New Approach Methodologies (NAMs) to evaluate chemical- associated toxicity. Since the liver is a primary target organ for xenobiotics, our objective is to use both 2D and 3D HepaRG models combined with High-Content Analysis (HCA) for chemical mechanistic toxicity profiling. HepaRG models were exposed to eight chemicals (Chlorothalonil, Tebuconazole, Thioacetamide, Benzoyl peroxide, Diethyl maleate, clofibrate, indeno[1,2,3-cd]pyrene, 3-methylcholanthrene) for 72h with daily media renewal. Cellular endpoints including cytotoxicity, oxidative stress, mitochondrial dysfunction, lipid accumulation and the pro-inflammatory response were quantified. Additionally, four chemicals were added in this study to test chemicals having different MOA and to demonstrate the sensitivity of the 3D HepaRG spheroid model (FICZ, Diuron, 12-O-Tetradecanoylphorbol-13-acetate, Azoxystrobin). Our findings revealed that 3D HepaRG cells exhibited more pronounced positive responses to chemical treatment compared to the 2D HepaRG cells. In addition to the chemical-specific toxicity profiling generated by HCA, we identified correlations between different cellular alterations such as mitochondrial dysfunction, dysregulated lipid metabolism and oxidative stress in the treated 3D HepaRG spheroids. Overall, this approach proposed in this study provides a rapid, human-relevant in vitro method that enhances the predictive power of NAMs for chemical associated toxicity.</p>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":" ","pages":"154280"},"PeriodicalIF":4.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087359","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":"Neurological alterations in adult female rats developmentally exposed to a glyphosate-based herbicide: Potential role of the immune system","authors":"Cristina Eugenia Gallegos ,&nbsp;Mariana Bartos ,&nbsp;Fernanda Gumilar ,&nbsp;Diego Nicolás Nabaes Jodar ,&nbsp;Ileana Lencinas ,&nbsp;Cristina Bras ,&nbsp;Betina Noemí García ,&nbsp;Jorge Andrés Delbés ,&nbsp;Sergio Dominguez ,&nbsp;Carlos Javier Baier","doi":"10.1016/j.tox.2025.154279","DOIUrl":"10.1016/j.tox.2025.154279","url":null,"abstract":"<div><div>Despite the increasing evidence about the adverse consequences of early exposure to Glyphosate (Gly) and Gly-based herbicides (GlyBHs) on the central nervous system (CNS), little is known about the effects of this herbicide on the developing immune system. We have previously described that oral exposure of rats to a GlyBH during pregnancy and lactation induces neurobehavioral alterations, brain oxidative stress imbalance, and impairment in the activity of enzymes involved in the glutamatergic and cholinergic systems in adulthood. The purpose of this study was to investigate further the mechanisms of neurotoxicity exerted by GlyBHs and to explore a possible link between their effects on the CNS and the immune system. For this purpose, pregnant Wistar rats were orally exposed to 0.4 % GlyBH from gestational day 0 until weaning (postnatal day (PND) 21), and a series of behavioural and biochemical analyses were conducted in PND90 female pups. Haematological and serological parameters were affected by exposure to the herbicide. In addition, GlyBH altered lactate dehydrogenase (LDH) activity and the redox status in specific brain areas, and decreased the number of astrocytes in the hippocampus of perinatally exposed rats. Finally, GlyBH-treatment induced a depressive-like behaviour evaluated by the forced swim test. Taken together, the findings of the present study demonstrate that exposure to a Gly-containing herbicide during pregnancy and lactation induced long-lasting changes in the immune system of 90-day-old female offspring, which in turn could affect their CNS.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"518 ","pages":"Article 154279"},"PeriodicalIF":4.6,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145070572","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 oral exposure to finasteride and different doses of minoxidil induces testicular and epididymal alterations in adult Balb/c mice","authors":"Francielle de Fátima Viana Santana ,&nbsp;João Vitor de Souza Ferreira ,&nbsp;Diane Costa Araujo ,&nbsp;Ana Paula Soares Rafael ,&nbsp;Cláudia Fernanda Aguiar Freitas ,&nbsp;Luiz Otávio Guimarães-Ervilha ,&nbsp;John Lennon de Paiva Coimbra ,&nbsp;Mariana Machado-Neves ,&nbsp;Guilherme Mattos Jardim Costa ,&nbsp;Janaina da Silva ,&nbsp;Sérgio Luis Pinto da Matta","doi":"10.1016/j.tox.2025.154278","DOIUrl":"10.1016/j.tox.2025.154278","url":null,"abstract":"<div><div>Oral finasteride and topical minoxidil are approved treatments for androgenetic alopecia, while low-dose oral minoxidil has emerged as a promising off-label alternative. Despite its vasodilatory and androgen-modulating properties, the minoxidil effects on male reproductive health remain poorly understood. Given its growing off-label use and potential reproductive impact, this study aimed to evaluate the histopathological, hormonal, and oxidative stress effects of oral minoxidil on the testes and epididymides of adult Balb/c mice. A total of 120 animals were divided into six groups (n = 20) receiving daily oral doses of water, vehicle, finasteride (5 mg/kg), or minoxidil (2.5, 5, or 7.5 mg/kg). Half were euthanized after 42 days and the remainder after 84 days of treatment. On the 42nd day, both minoxidil and finasteride induced testicular structural alterations, including vacuolization of the seminiferous epithelium, reduction in seminiferous epithelium height, and increase in the proportion of Leydig cells. In the minoxidil-treated groups, these alterations were accompanied by decreased serum estradiol levels and oxidative imbalance, suggesting these might be underlying mechanisms of minoxidil-induced reproductive toxicity. After 84 days, although no significant changes were observed in the estradiol levels and oxidative status, testicular structural alterations persisted, characterized by continued vacuolization of the seminiferous epithelium and decreased seminiferous epithelium proportion after finasteride and minoxidil treatments. Although no dose-dependent minoxidil effect was observed, the dose of 5 mg/kg more frequently induced alterations. Histological epididymal changes were identified with both drugs at both time points. However, only finasteride significantly reduced sperm transit time (at 42 and 84 days) and cauda sperm count (at 84 days). These results suggest that while both minoxidil and finasteride induce broader testicular alterations, finasteride significantly affects epididymal function. This study highlights potential reproductive risks associated with long-term oral minoxidil use and emphasizes the importance of clinical studies assessing its safety in male reproductive health, particularly in individuals of reproductive age.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"518 ","pages":"Article 154278"},"PeriodicalIF":4.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058677","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":"Differential effects of mercury compounds on mutagenicity, genotoxicity and repair of UV-DNA damage","authors":"Anna Cyran ,&nbsp;Giorgiana Madalina Ursu ,&nbsp;Casey Krawic,&nbsp;Anatoly Zhitkovich","doi":"10.1016/j.tox.2025.154277","DOIUrl":"10.1016/j.tox.2025.154277","url":null,"abstract":"<div><div>Mercury (Hg) is a global contaminant that is present in human diet as methylmercury (MeHg). Recent studies linked MeHg exposure with high risks of skin cancers. It is unknown whether MeHg is directly genotoxic in skin cells or able to enhance mutagenic effects of UV radiation. We examined mutagenicity and genotoxicity of MeHg and its metabolite inorganic Hg^2 + (iHg) and their impact on processing of carcinogenic UV-DNA damage. We found that iHg and MeHg were both nonmutagenic in the <em>Hprt</em> assay in rodent CHO cells. iHg but not MeHg strongly enhanced mutagenicity of UV-B without changes in repair of mutagenic cyclobutane pyrimidine dimers (CPDs). In human keratinocytes, iHg increased genotoxic stress and formation of micronuclei by UV-B which occurred in cells with both normal and inactive nucleotide excision repair of UV-DNA damage. Repair of UVB-induced CPDs and 6–4 photoproducts in keratinocytes was unaffected by iHg or MeHg. Formation of micronuclei in human keratinocytes by MeHg and UV-B was additive, indicating their independence. Thus, iHg(II) was not directly mutagenic/genotoxic but it enhanced mutagenicity and clastogenicity of UV-DNA damage without interference with its repair. MeHg did not alter DNA repair or mutagenicity/genotoxicity of UV-B but it acted as a clastogen in human keratinocytes.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"518 ","pages":"Article 154277"},"PeriodicalIF":4.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145018539","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":"Corrigendum to ‘β-Estradiol antagonizes the inhibitory effects of caffeine in BMMSCs via the ERβ-mediated cAMP-dependent PKA pathway’ [Toxicology 394 (2018) 1–10]","authors":"Chaowei Wang,&nbsp;Yi Zhou,&nbsp;Xiaoxu Guan,&nbsp;Mengfei Yu,&nbsp;Huiming Wang","doi":"10.1016/j.tox.2025.154272","DOIUrl":"10.1016/j.tox.2025.154272","url":null,"abstract":"","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"518 ","pages":"Article 154272"},"PeriodicalIF":4.6,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993357","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":"Mechanisms of podophyllotoxin-induced enterotoxicity: A multi-omics integration of gut microbiota, short-chain fatty acids, and inflammatory mediators","authors":"Yanli Lu ,&nbsp;Yunge Liu ,&nbsp;Xiaoyang Bai ,&nbsp;Tao Jiang ,&nbsp;Xiaowan Chen ,&nbsp;Yanqiu Wang ,&nbsp;Peipei Du ,&nbsp;Yuhan Sun ,&nbsp;Chuanxin Liu ,&nbsp;Jiajia Duan","doi":"10.1016/j.tox.2025.154274","DOIUrl":"10.1016/j.tox.2025.154274","url":null,"abstract":"<div><div>Podophyllotoxin (PPT), a lignan extracted from the roots and stems of <em>Podophyllum</em> species, exhibits significant enterotoxicity that limits its clinical application. However, its underlying mechanisms remain unclear. This study aimed to elucidate the mechanisms underlying PPT-induced enterotoxicity. Changes in body weight, fecal morphology, toxic phenotypes, and histopathological features were evaluated. 3D reconstruction, 16S rRNA sequencing, targeted short-chain fatty acids (SCFAs) analysis, and inflammatory cytokine assays were performed. The findings demonstrated that PPT induced pathological changes in rats, including weight loss, diarrhea, and colonic damage. PPT administration significantly reduced beneficial bacteria such as <em>Lactobacillus</em>, while increasing harmful bacteria such as <em>Escherichia-Shigella</em>. The predicted pathways of bacterial invasion of epithelial cells and lipopolysaccharide biosynthesis were significantly upregulated. Levels of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), were also increased. Additionally, the expression of undecaprenyl-diphosphate synthase (UPPS) and SCFAs production was reduced. These findings indicate that PPT may alter gut microbial composition, increase <em>Escherichia-Shigella</em> invasion in the intestinal epithelial cells, promote lipopolysaccharide production, enhance the release of pro-inflammatory cytokines, including TNF-α and IL-6, and inhibit UPPS expression and SCFAs generation, collectively contributing to enterotoxicity. This study provides novel insights into the mechanisms behind PPT-induced enterotoxicity, which is essential for preventing and treating PPT toxicity.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"518 ","pages":"Article 154274"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932630","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":"Characterization and comparison of respiratory toxicity induced by sublethal poisoning to two organophosphorus compounds: A pesticide and a sarin structural analog in mice","authors":"Anne-Sophie Hanak,&nbsp;Florent Fémy,&nbsp;Asma Berriche,&nbsp;Chloé Reymond,&nbsp;Typhaine Rotiel,&nbsp;Méliati Madi,&nbsp;Nina Jaffré,&nbsp;André-Guilhem Calas,&nbsp;Grégory Dal Bo,&nbsp;Karine Thibault","doi":"10.1016/j.tox.2025.154276","DOIUrl":"10.1016/j.tox.2025.154276","url":null,"abstract":"<div><div>The chemical risk associated with the use of organophosphorus nerve agents remains a major concern, as highlighted by recent international events (e.g., Syrian conflict, Novichok poisoning incidents) and the tense geopolitical climate. Concurrently, the use of organophosphorus pesticides continues to represent a major global public health challenge, resulting in numerous poisonings and fatalities each year. Organophosphorus compounds exert their toxic effects by irreversibly inhibiting cholinesterase enzymes, disrupting cholinergic signaling within the affected organism. This disruption impairs vital functions and, without appropriate medical intervention, can result in respiratory failure and death. However, whether differences in the molecular and physiological mechanisms underlying organophosphorus compound-induced respiratory failure between pesticides and nerve agents exist remains poorly defined. This study aimed to characterize and compare respiratory toxicity in mice exposed to two sublethal organophosphorus compounds: a pesticide (paraoxon) and a sarin structural analog (NIMP). Respiratory ventilation in mice was monitored using double-chamber plethysmography. Cholinesterase activity and inflammatory biomarkers were quantified in blood and tissues involved in respiration. Both compounds dose-dependently affected ventilatory function of the mice, reducing respiratory rate and minute volume and increasing specific airway resistance. No significant differences were observed between the two organophosphorus compounds in these effects. However, lungs and diaphragm triggered a rapid inflammatory response, depending on the specific organophosphorus compound tested. While NIMP exposure increased IL-6 expression, potentially involving the NF-κB pathway, POX exposure upregulated IL-1ß expression without activating NF-κB. Thus, exposure to POX or NIMP similarly impaired ventilatory function in mice, but distinct signaling pathways appear to be involved.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"518 ","pages":"Article 154276"},"PeriodicalIF":4.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993312","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}