Toxicology and applied pharmacology最新文献

{"title":"Impact of spinal anesthesia on myocardial damage, ultrastructure and cellular mechanisms in rats undergoing thoracic incision surgery","authors":"Tsun-Jui Liu ,&nbsp;Vanita Shih ,&nbsp;Yueh-Chiao Yeh ,&nbsp;Wen-Lieng Lee ,&nbsp;Li-Chuan Wang ,&nbsp;Hui-Chin Lai","doi":"10.1016/j.taap.2025.117349","DOIUrl":"10.1016/j.taap.2025.117349","url":null,"abstract":"<div><h3>Aims</h3><div>This study aimed to investigate the impact of surgery on cardiac injury and microscopic ultrastructural changes in the heart, as well as the potential protective cellular mechanisms of spinal anesthesia.</div></div><div><h3>Methods</h3><div>Male Sprague-Dawley rats were randomly assigned to four groups: Control (regular rats), Sham (received spinal saline injection), Surgery (received spinal saline followed by surgery) and Bupivacaine (received spinal bupivacaine 0.5 %, 50 μL followed by surgery), and Bupivacaine (received spinal bupivacaine 0.5 %, 50 μL followed by surgery). The serum and hearts of the rats were assessed for troponin I, NT-proBNP, electron microscopy, catecholamines, markers of oxidative stress and endoplasmic reticulum stress, as well as apoptosis and autophagy.</div></div><div><h3>Results</h3><div>After surgery, the hearts showed signs of injury, with decreased tissue troponin I and elevated NT-proBNP levels. Electron microscopy revealed mitochondrial swelling, disarrangement and cytosolic vacuoles. Serum epinephrine levels and expression of β1 and β2 adrenergic receptors were elevated. Serum nitrate and nitrite levels (markers of oxidative stress), along with the ER stress indicator GRP78 and autophagy indicators LC3 and LAMP-1, were heightened, and cardiomyocyte apoptosis increased. These effects can be mitigated with the use of spinal bupivacaine.</div></div><div><h3>Conclusions</h3><div>Surgery can cause ultrastructural and cellular damage, elevate sympathetic activity, oxidative stress, and endoplasmic reticulum stress, leading to autophagy and cardiomyocyte apoptosis. Spinal anesthesia can protect the heart from these injuries.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"499 ","pages":"Article 117349"},"PeriodicalIF":3.3,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143850688","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":"H3K9/18 lactylation regulates DNA damage due to nickel exposure in human bronchial epithelial cells","authors":"Xiaomin Xie ,&nbsp;Chaowei Wen ,&nbsp;Quekun Peng ,&nbsp;Daimin Xiang ,&nbsp;Xinyi Pan ,&nbsp;Xinmei Lan ,&nbsp;Zijian Chen ,&nbsp;Xiaohui Hua ,&nbsp;Guiying Wang ,&nbsp;Chuanshu Huang","doi":"10.1016/j.taap.2025.117347","DOIUrl":"10.1016/j.taap.2025.117347","url":null,"abstract":"<div><div>Nickel, a well-known heavy metal with lung carcinogenic properties, is recognized for its effects on cellular metabolism, oxidative stress, and gene expression. While these cellular alterations have prompted investigations into its potential impact on histone modifications, specific associations with histone lactylation remain under exploration. In the present study, we demonstrate that nickel exposure induces lactylation of histone H3 at lysines 9 (H3K9) and 18 (H3K18), accompanied by reactive oxygen species (ROS) accumulation and DNA damage in human bronchial epithelial Beas-2B cells. Inhibition of H3K9 and H3K18 lactylation, achieved by overexpressing mutated H3K9R and H3K18R, respectively, markedly abolishes ROS generation and DNA damage caused by nickel exposure. This highlights the novel biological effects of H3K9 and H3K18 lactylation in nickel-induced lung toxicity. Mechanistic investigations show that nickel-induced lactylation of H3K9 and H3K18 is mediated by elevated LDHA expression, leading to lactate accumulation, which results from the upregulation of <em>LDHA</em> mRNA transcription through HIF-1α/c-Jun axis and enhanced LDHA protein stability <em>via</em> TNF-α-mediated induction of HSP70, respectively. Our findings uncover a novel effect of nickel exposure on histone H3 lactylation and its biological impact on ROS accumulation and DNA damage through the HIF-1α/c-Jun/LDHA and TNF-α/HSP70/LDHA pathways. These results provide significant insights into the role of histone lactylation in heavy metal-induced lung toxicity.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"499 ","pages":"Article 117347"},"PeriodicalIF":3.3,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143854756","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":"Demethylzeylasteral inhibits osteosarcoma cell proliferation by regulating METTL17-mediated mitochondrial oxidative phosphorylation","authors":"Jingyu Cao ,&nbsp;Haotian Zhang ,&nbsp;Chengbo Wang ,&nbsp;Lihua He ,&nbsp;Ya Li ,&nbsp;Zimeng Wang ,&nbsp;Xianxiao Li ,&nbsp;Faisal Aziz ,&nbsp;Minglei Yang ,&nbsp;Xiangzhan Zhu","doi":"10.1016/j.taap.2025.117348","DOIUrl":"10.1016/j.taap.2025.117348","url":null,"abstract":"<div><h3>Abstract</h3><div>Osteosarcoma (OS) represents the most common primary bone malignancy, characterized by substantial disability and mortality, thereby underscoring the critical need for more effective therapeutic interventions to improve clinical outcomes. Demethylzeylasteral (DEM) is a bio-active compound has been reported for its anti-tumor properties through various mechanisms. Nonetheless, the specific effects of DEM on OS have yet to be fully elucidated. This study demonstrated that DEM significantly inhibited OS cell proliferation both <em>in vitro</em> and <em>in vivo</em>. Mechanistically, DEM impairs mitochondrial OXPHOS by targeting METTL17, a known regulator of mitochondrial translation, resulting in reduced ATP production. Subsequent investigations revealed that METTL17 knockdown exerts potent anti-tumor effects in OS, significantly suppressing both <em>in vitro</em> cell proliferation and <em>in vivo</em> xenograft tumor growth. Furthermore, METL17 overexpression significantly alleviated the inhibitory effects of DEM on cell proliferation, while restoring ATP production and oxygen consumption rates. These findings suggest that DEM impedes OS growth by inducing mitochondrial dysfunction through targeting METTL17, thereby highlighting a novel therapeutic strategy and potential molecular target for OS treatment.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"499 ","pages":"Article 117348"},"PeriodicalIF":3.3,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143852344","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":"AnxA2-EGFR pro-inflammatory signaling potentiates EMT-induced fibrotic stress and its modulation by short-chain fatty acid butyrate in idiopathic pulmonary fibrosis","authors":"Vinay C. Sangamesh ,&nbsp;Pavan K. Jayaswamy ,&nbsp;M. Vijaykrishnaraj ,&nbsp;Nithin K. Kuriakose ,&nbsp;B.H. Giridhar ,&nbsp;K. Jayaprakash Shetty ,&nbsp;Prakash Patil ,&nbsp;Sukanya Shetty ,&nbsp;Roopa Bhandary ,&nbsp;Praveenkumar Shetty","doi":"10.1016/j.taap.2025.117342","DOIUrl":"10.1016/j.taap.2025.117342","url":null,"abstract":"<div><div>Idiopathic pulmonary fibrosis (IPF) is a debilitating lung disease characterized by excessive extracellular matrix deposition, leading to irreversible lung scarring. This study explores the underlying molecular mechanisms of IPF and delves into membrane-anchored synergism between EGFR and AnxA2, which amplifies fibrotic stress and plays a pivotal role in promoting pulmonary fibroblast activation and fibrosis. Indeed, these interactions create a synergistic effect that promotes the loss of epithelial traits and the transition to a mesenchymal phenotype, thereby contributing to fibrotic stress and disease progression. In addition, this study also explores the potential of butyrate, a short-chain fatty acid, as a therapeutic agent in reducing fibrotic stress by modulating AnxA2-EGFR signaling. Pre-treatment with butyrate significantly dampens AnxA2-EGFR signaling and Galectin-3 expression, effectively curbing prolonged EGFR phosphorylation. The suppression of upstream signaling leads to a reduction in the angiogenic marker VEGF and a decrease in pro-inflammatory mediators such as TNF-α and IL-6. Collectively, our findings highlight the critical role of EGFR-AnxA2 signaling and Galectin 3 in the pathogenesis of IPF, and highlight butyrate as a potential therapeutic agent for alleviating fibrotic stress.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"499 ","pages":"Article 117342"},"PeriodicalIF":3.3,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838874","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 protective effects of tectoridin on bone fractures against oxidative stress via the inhibition of NF-κB and apoptotic pathways in ovariectomized rats","authors":"Yanwei Fan,&nbsp;Yaokun Yu,&nbsp;Peng Yan","doi":"10.1016/j.taap.2025.117345","DOIUrl":"10.1016/j.taap.2025.117345","url":null,"abstract":"<div><div>Oxidative stress and inflammation lead to high bone turnover, contributing to osteoporosis caused by estrogen deficiency in postmenopausal women. Tectoridin, an isoflavonoid with antioxidant and anti-inflammatory properties, was evaluated for its protective effects in ovariectomized (OVX) rats, a model of postmenopausal osteoporosis. Five groups of female rats (<em>n</em> = 6) were established: normal, OVX control, OVX treated with tectoridin at 10 and 20 mg/kg bw, and OVX treated with estrogen, over a four-week period. Tectoridin treatment resulted in reduced body weight and improved femur weight and thickness. Serum E2, calcium, and phosphate levels increased, while alkaline phosphatase (ALP) levels decreased after treatment. Additionally, tectoridin altered lipid profiles by decreasing total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL), while increasing high-density lipoprotein (HDL). The treatment elevated serum bone-specific alkaline phosphatase (BALP) and procollagen type I N-terminal propeptide (PINP) levels, and decreased levels of bone resorption markers CTX-1 and NTx. Tectoridin upregulated osteogenic markers Runx2, Osx, and BMP2, suggesting enhanced bone properties. Moreover, it reduced lipid peroxidation and increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, indicating reduced oxidative stress. Tectoridin also inhibited inflammatory proteins and exhibited anti-apoptotic effects on Bax/Caspase3 and Bcl2 expression. This study highlights the potential of tectoridin in modulating oxidative stress, inflammation, and improving bone remodeling in OVX rats, making it a candidate for managing postmenopausal osteoporosis.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"500 ","pages":"Article 117345"},"PeriodicalIF":3.3,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935526","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":"Protective effects of melatonin against 5-fluorouracil-induced cardiotoxicity in rats: A comprehensive evaluation of oxidative, inflammatory, and apoptotic pathways","authors":"Razieh Mansoori ,&nbsp;Manoochehr Ashrafpour ,&nbsp;Mohammad Hossien Asghari ,&nbsp;Ravieh Golchoobian ,&nbsp;Seyed Mohammad Hosseini ,&nbsp;Russel J. Reiter ,&nbsp;Bardia Karim ,&nbsp;Ali Akbar Moghadamnia ,&nbsp;Sohrab Kazemi","doi":"10.1016/j.taap.2025.117343","DOIUrl":"10.1016/j.taap.2025.117343","url":null,"abstract":"<div><h3>Background</h3><div>Cardiotoxicity is a serious adverse effect of 5-fluorouracil (5-FU) a common chemotherapeutic agent. This study aimed to evaluate the protective effects of melatonin (MLT) against 5-fluorouracil (5-FU)-induced cardiotoxicity in rats, focusing on oxidative stress, inflammatory pathways, gene expression, electrocardiographic and histopathological changes.</div></div><div><h3>Materials and methods</h3><div>Twenty-five male Wistar rats were divided into five groups. The animals received either MLT at doses of 2.5, 5, or 10 mg/kg/day, 5-FU at 50 mg/kg (i.p.), or a combination of both treatments. Cardiotoxicity was assessed through electrocardiography, cardiac enzymes, oxidative stress markers, and histopathology.</div></div><div><h3>Results</h3><div>5-FU treatment significantly increased oxidative stress markers and inflammatory mediators while causing histopathological damage in heart tissues. Co-administration of MLT with 5-FU significantly mitigated these effects by reducing oxidative damage, as evidenced by lower levels of malondialdehyde (MDA), nitric oxide (NO), and myeloperoxidase (MPO). Additionally, MLT enhanced antioxidant activity, as reflected by increased levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in heart tissues. Gene expression analysis further confirmed that MLT treatment reduced the elevated levels of COX-2 and VEGF, which are critical players in the inflammatory process. Histopathological examination demonstrated that MLT preserved the structural integrity of myocardial tissues, reducing 5-FU-induced damage score in a dose-dependent manner. Furthermore, MLT co-administration significantly attenuated the rise in cardiac biomarkers, including LDH, AST, and CK-MB, associated with 5-FU-induced cardiotoxicity.</div></div><div><h3>Conclusion</h3><div>These findings highlight that MLT, through its antioxidant and anti-inflammatory properties, exerts a protective effect against 5-FU-induced toxicity, suggesting its therapeutic potential for improving cardiovascular health during chemotherapy.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"499 ","pages":"Article 117343"},"PeriodicalIF":3.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143847676","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":"Quercetin-loaded PEGylated liposomes alleviate testicular dysfunction in alloxan-induced diabetic rats: The role of Kisspeptin/Neurokinin B/Dynorphin pathway","authors":"Mohamed Fouad Mansour ,&nbsp;Amany Behairy ,&nbsp;Mahmoud Mostafa ,&nbsp;Tarek Khamis ,&nbsp;Amira Ebrahim Alsemeh ,&nbsp;Noura Mohammed Qenawy Ahmed ,&nbsp;Mahran Mohamed Abd El-Emam","doi":"10.1016/j.taap.2025.117337","DOIUrl":"10.1016/j.taap.2025.117337","url":null,"abstract":"<div><div>Diabetes mellitus (DM) is a chronic metabolic disorder that can lead to serious complications, including testicular dysfunction. This dysfunction is considered a significant cause of male infertility. Quercetin (Que), a naturally existing flavonoid with versatile biological functions, has limited water solubility and low bioavailability. The current study was designed to develop a bioavailable formulation of Que. via encapsulating it in PEGylated liposomes (Que-PEG-Lip) and determine whether this formulation is effective in the treatment of alloxan-induced testicular injury via targeting Kisspeptin/Neurokinin B/Dynorphin/steroidogenesis signaling pathway. Thirty-two male Sprague Dawley rats were randomly divided into four groups: Control, alloxan-induced diabetes with testicular dysfunction (ALX), ALX + metformin (MET) and ALX + Que-PEG-Lip. The results showed that treatment of ALX group with Que-PEG-Lip significantly improved the alteration of glycemic index, serum reproductive hormones, testicular antioxidant status, testicular Kiss-1, androgen receptor (AR), and proliferation marker protein (ki67) immunoexpression in compared to ALX group. Moreover, the treatment of ALX group with Que-PEG-Lip regulated the Kisspeptin/Neurokinin B/Dynorphin/steroidogenesis pathway gene expression. Interestingly, the outcomes of the molecular docking analysis revealed a strong agonistic effect of Que. on the kisspeptin, neurokinin, and dynorphin receptors. In conclusion, Que-PEG-Lip mitigated the testicular dysfunction in alloxan-induced diabetic rats via regulation of hypothalamic-pituitary-gonadal axis signaling pathway and alleviation the testicular oxidative stress.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"499 ","pages":"Article 117337"},"PeriodicalIF":3.3,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843374","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":"Differences in chemotherapeutic drug sensitivity before and after patient-derived tumor organoid construction","authors":"Fang Shao ,&nbsp;Xin Huang ,&nbsp;Zhihong Ma ,&nbsp;Liqin Li ,&nbsp;Chunjian Qi","doi":"10.1016/j.taap.2025.117340","DOIUrl":"10.1016/j.taap.2025.117340","url":null,"abstract":"<div><h3>Background</h3><div>Patient-derived organoids (PDOs) have emerged as promising preclinical models for various tumor types. This study aimed to optimize the process of constructing 3D organoid models and facilitate the development of personalized therapies for gastric and colon cancers.</div></div><div><h3>Methods</h3><div>Tumor tissues were divided into two parts: one part was dissociated into a single-cell suspension, and the other part was used to culture tumor organoids. RNA sequencing (RNA-seq) was performed on both tumor cells and cultured organoids. Four chemotherapeutic agents-Oxaliplatin (L-OHP), Gemcitabine (GEM), 5-Fluorouracil (5-FU), and Paclitaxel (PTX)-were utilized to assess cytotoxicity and proliferation in both organoids and freshly isolated tumor cells, then the effects of these agents were evaluated.</div></div><div><h3>Results</h3><div>Organoids were successfully established from both surgically resected and biopsy-derived tumor tissues. Phenotypic analysis indicated that the organoids retained the histological features and expression profiles of the original tumors. Notably, the morphological characteristics of the organoids remained stable across passages, demonstrating robust growth over time. Differentially expressed genes were identified in both gastric and colon cancer PDOs. GO and KEGG pathway analyses revealed similar gene enrichment in gastric and colon PDOs. Both gastric and colon cancer PDOs exhibited increased significant sensitivity to PTX and 5-FU compared to freshly isolated cancer cells. Furthermore, the expression of most stemness-related genes was reduced after organoid culture.</div></div><div><h3>Conclusions</h3><div>We successfully established organoid models that demonstrated robust growth and heightened drug sensitivity compared to freshly isolated tumor cells. These findings suggest that caution should be exercised when interpreting drug sensitivity results from organoid-based assays.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"499 ","pages":"Article 117340"},"PeriodicalIF":3.3,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826462","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":"Estrogenic and androgenic activity of tert-butyl phenolic antioxidants assessed by in vitro receptor transcriptional activation and their association with in silico molecular docking analysis","authors":"Ngoc Minh-Hong Hoang,&nbsp;Kwangsik Park","doi":"10.1016/j.taap.2025.117344","DOIUrl":"10.1016/j.taap.2025.117344","url":null,"abstract":"<div><div>Tert-butyl phenolic antioxidants (TBP-AOs) are utilized in a variety of consumer products, including food packaging, daily use items, and industrial applications. Their widespread use raises significant concerns regarding potential health risks, particularly endocrine disruption. However, our understanding of many TBP-AOs concerning endocrine systems remains limited, underscoring the need for screening of their hormonal activities and better insight into their adverse outcome pathways (AOPs). Transcriptional activation (TA) assays are crucial experimental tools in the early stages of risk assessment. This study evaluated the estrogenic and androgenic characteristics of 30 TBP-AOs through TA assays in hERα-HeLa-9903 and 22Rv1/MMTV_GR-KO cell lines, respectively, augmented by docking simulation using CB-Dock2. Our findings identified 21 estrogen receptor (ER) agonists, one ER antagonist, and eight androgen receptor (AR) antagonists, with significant correlations between biological activity and docking scores for specific proteins: 1GWR_C4 and 7KBS_C2 for ERα, and 2AM9_C1 for AR. These results enhance our understanding of TBP-AOs' toxicity on the endocrine system and confirm that TA assays and docking are effective methods for evaluating their endocrine activities. This research lays the foundation for future studies on endocrine disruptors, aiming to elucidate the mechanisms underlying molecular initiating events and key events within AOPs for TBP-AOs and other chemicals.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"499 ","pages":"Article 117344"},"PeriodicalIF":3.3,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143834912","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":"Fudosteine attenuates lung inflammation in mice with PM2.5-induced asthma exacerbation by inhibiting pyroptosis via the NLRP3/caspase-1/GSDMD pathway","authors":"Jianling Liu ,&nbsp;Zhongpeng Li ,&nbsp;Zhangwen Li ,&nbsp;Aili Wang ,&nbsp;Xiaoyang Liao ,&nbsp;Zhangquan Liu ,&nbsp;Jian Wu","doi":"10.1016/j.taap.2025.117346","DOIUrl":"10.1016/j.taap.2025.117346","url":null,"abstract":"<div><div>This study aimed to explore the potential preventive effects of fudosteine (Fud) on PM2.5-induced asthma exacerbations in a murine model. BALB/c mice were randomly allocated into six groups: control, Fud, ovalbumin (OVA), OVA+Fud, OVA+PM2.5, and OVA+PM2.5 + Fud. An asthma model was established through OVA sensitization and challenge. Compared to the OVA group, PM2.5 exposure exacerbated allergic asthma, as evidenced by increased collagen fiber deposition, goblet cell metaplasia, mucus secretion, heightened airway inflammation, elevated total cell and eosinophil counts, and upregulated levels of interleukin (IL)-1β, IL-18, and NLRP3 expression in lung tissues. Notably, fudosteine treatment mitigated these pathological changes. Western blot analysis revealed that fudosteine significantly reduced the expression of NLRP3, caspase-1, gasdermin D (GSDMD), cleaved-caspase-1, and cleaved-GSDMD in lung tissues. In conclusion, fudosteine alleviated lung inflammation, collagen deposition, and mucus secretion in PM2.5-induced asthma exacerbation, potentially by inhibiting the NLRP3 inflammasome-mediated pyroptosis pathway.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"499 ","pages":"Article 117346"},"PeriodicalIF":3.3,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838875","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}