Toxicology and applied pharmacology最新文献

{"title":"Molecular mechanisms of andrographolide-induced kidney injury and senescence via SIRT3 inhibition","authors":"Yi Cai ,&nbsp;Liduan Huang ,&nbsp;Yanhong Hou ,&nbsp;Peiwen Pang,&nbsp;Ying Zhou,&nbsp;Xuan Zhang,&nbsp;Yiyin Long,&nbsp;Huajian Li,&nbsp;Halimulati Muhetaer,&nbsp;Man Zhang,&nbsp;Bo Wu","doi":"10.1016/j.taap.2025.117306","DOIUrl":"10.1016/j.taap.2025.117306","url":null,"abstract":"<div><div>Andrographolide, a diterpene compound derived from the medicinal plant <em>Andrographis paniculata</em>, possesses anti-inflammatory, antioxidant, antitumor, and antiviral properties. Injectable formulations containing andrographolide, such as Potassium Sodium Dehydroandrographolide Succinate for Injection (PSDS), are widely used in clinical practice to treat various diseases, including upper respiratory tract infections. However, clinical reports have highlighted that andrographolide-based herbal injections may induce acute kidney injury and other renal adverse effects, thereby restricting its clinical application. Despite these concerns, the molecular mechanisms underlying andrographolide-induced nephrotoxicity remain poorly understood. In this study, we demonstrated that andrographolide induces inflammation and fibrosis in renal tubular epithelial cells and mouse kidneys. Notably, we identified for the first time that andrographolide promotes cellular senescence in renal tubular epithelial cells and mouse kidneys while downregulating the expression and enzymatic activity of SIRT3. Mechanistic investigations revealed that andrographolide mediates kidney injury and senescence through inhibition of the SIRT3/p53 signaling pathway. Furthermore, andrographolide was found to disrupt the interaction between SIRT3 and p53, resulting in increased acetylation of p53 and upregulation of its downstream target genes involved in inflammation, fibrosis, and senescence. These findings elucidate the molecular mechanisms of andrographolide-induced nephrotoxicity and provide a scientific basis for developing strategies to reduce its toxic effects.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"498 ","pages":"Article 117306"},"PeriodicalIF":3.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670965","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":"Adrenergic receptor subtypes differentially influence acrolein-induced ventilatory, vascular leakage, and inflammatory responses","authors":"Devin I. Alewel ,&nbsp;Stephen H. Gavett ,&nbsp;Katherine M. Rentschler ,&nbsp;Mette C. Schladweiler ,&nbsp;Colette N. Miller ,&nbsp;Paul A. Evansky ,&nbsp;Thomas W. Jackson ,&nbsp;Wanda C. Williams ,&nbsp;Urmila P. Kodavanti","doi":"10.1016/j.taap.2025.117303","DOIUrl":"10.1016/j.taap.2025.117303","url":null,"abstract":"<div><div>Adrenergic receptors (AR) are manipulated therapeutically for the treatment of pulmonary and cardiovascular diseases; however, their role in air pollutant-induced respiratory effects is poorly understood. We examined the contribution of AR-subtypes in acrolein-induced respiratory effects through selective receptor inhibition. We pre-treated 12-week-old male Wistar-Kyoto rats intraperitoneally daily for 9-days with subtype-specific AR antagonists prazosin (PRZ, α1-AR antagonist; 2-mg/kg-day), yohimbine (YOH, α2-AR antagonist; 5-mg/kg-day), or propranolol (PROP, β-AR antagonist; 10-mg/kg-day). On day-8 and day-9 of treatment, rats were exposed nose-only to air or acrolein (1.6 or 3.2 ppm), ∼4 h/day. Head-out plethysmography during exposure on Day-9 revealed overall concentration-dependent acrolein-related reduced ventilatory capacity, which was exacerbated in PRZ- and YOH-treated animals. Nasal (NALF) and bronchoalveolar lavage fluid (BALF), and blood samples were collected on day-9. Plasma epinephrine levels did not change; however, corticosterone decreased in YOH- and PROP-treated air-exposed animals. Adrenal and spleen weights were higher in PRZ-treated animals. Acrolein, 3.2-ppm depleted circulating lymphocytes in saline-treated and increased neutrophils in PRZ- and YOH-treated animals. NALF and BALF analysis indicated 3.2-ppm acrolein-induced neutrophilic and lymphocytic inflammation (NALF&gt;BALF), which was exacerbated in lung of PRZ- and YOH-treated rats and slightly dampened in PROP-treated rats. However, acrolein-induced vascular protein leakage and increases in inflammatory cytokines in NALF were reduced by PROP-treatment. In conclusion, this study highlights sympathetically-mediated adrenoreceptor influence on acrolein-indued respiratory health effects, and AR subtype-specific modulation of breathing, hemodynamic, and inflammatory responses. These results have broader translational implications, as those receiving adrenergic agonistic/antagonistic therapies might experience variable air pollution-related respiratory health effects.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"498 ","pages":"Article 117303"},"PeriodicalIF":3.3,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658724","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":"Metabolomic and molecular analysis reveals multiple pathways of TBBPA-induced developmental toxicity in zebrafish embryos","authors":"Qian Xu ,&nbsp;Ruixi Gan ,&nbsp;Qing Wang ,&nbsp;Peizhao Cheng ,&nbsp;Ziyun Hu ,&nbsp;Junsong Wang","doi":"10.1016/j.taap.2025.117295","DOIUrl":"10.1016/j.taap.2025.117295","url":null,"abstract":"<div><div>Tetrabromobisphenol A (TBBPA), a commonly utilized flame retardant, presents potential risks to both environmental and human health, with particular concern regarding its impact on embryonic development.This study employed zebrafish embryos as a model organism to investigate the comprehensive toxicological effects of TBBPA exposure, integrating metabolomics analysis with molecular and biochemical approaches. Embryos exposed to TBBPA concentrations ranging from 0.5 to 1.5 mg/L exhibited significant dose-dependent developmental abnormalities, including pericardial edema, yolk sac enlargement, and body axis curvature. At 96 h, we observed 50 % mortality at 1 mg/L. At 144 h of exposure to 0.1 mg/L TBBPA, automated behavioral analysis revealed significant changes in larval swimming patterns, characterized by reduced total distance moved, shortened active swimming time, impaired acceleration parameters, and abnormal spatial distribution. UHPLC-Q-TOF-MS-based metabolomics analysis revealed substantial perturbations in multiple biochemical pathways, particularly affecting neurotransmitter metabolism, energy homeostasis, and oxidative stress responses. TBBPA exposure significantly disrupted dopamine and serotonin metabolism, evidenced by altered enzyme expression and metabolite levels. Notable changes in oxidative stress markers, including GSH, MDA, and SOD, indicated significant cellular damage, while inflammatory responses showed dysregulation of both pro- and anti-inflammatory cytokines. Energy metabolism was comprehensively affected, with disruptions in glycolysis, TCA cycle, and amino acid metabolism pathways. The study identified key metabolic signatures of TBBPA toxicity and elucidated the interconnected mechanisms underlying its developmental impacts, providing valuable insights for environmental risk assessment and regulatory considerations. These findings emphasize the complex nature of TBBPA toxicity and highlight the need for careful evaluation of its environmental impact, particularly concerning early developmental exposure.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"498 ","pages":"Article 117295"},"PeriodicalIF":3.3,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143637040","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":"2-Dodecyl-6-Methoxycyclohexa-2,5-Diene-1,4-Dione from Averrhoa carambola L. roots: Suppressing hepatocellular carcinoma progression through ROS accumulation and p53 pathway-mediated apoptosis","authors":"Meifeng Chen ,&nbsp;Hongbing Pang ,&nbsp;Thi Thai Hoa Pham ,&nbsp;Yongfei He ,&nbsp;Qiang Gao ,&nbsp;Yuan Liao ,&nbsp;Chunyi Zhu ,&nbsp;Linqian Chen ,&nbsp;Guohong Yan ,&nbsp;Shutian Mo ,&nbsp;Chuangye Han","doi":"10.1016/j.taap.2025.117296","DOIUrl":"10.1016/j.taap.2025.117296","url":null,"abstract":"<div><div>This study explores the anti-tumor effects of 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD), a compound derived from <em>Averrhoa carambola</em> L roots, on hepatocellular carcinoma (HCC) cells and a xenograft mouse model, focusing on its underlying mechanisms. Cell viability following DMDD treatment was assessed using the CCK-8 assay. Flow cytometry determined changes in cell cycle distribution and apoptosis rates, while migration and invasion capabilities were assessed using wound healing and transwell assays, respectively. Transcriptome sequencing (RNA-seq) was conducted to analyze differential gene expression and pathway enrichment. <em>Z</em>-VAD-FMK, a pan-caspase inhibitor, was used to confirm the apoptotic mechanism induced by DMDD. The expression levels of p53, Bax, Bcl-2, and cleaved caspase 3 were quantified via Western blot analysis. A xenograft mouse model was developed to assess the in vivo effects of DMDD on HCC. DMDD suppressed proliferation, migration, and invasion, and induced apoptosis in Huh7 and Hep3b cells. RNA-seq revealed significant enrichment of p53 and apoptosis signaling pathways among differentially expressed genes. DMDD downregulated Bcl-2 expression and upregulated p53, Bax and cleaved caspase 3. In addition, <em>Z</em>-VAD-FMK partially inhibited DMDD-induced apoptosis. DMDD also inhibited tumor growth in mice. DMDD effectively inhibited tumor growth in HCC cell lines and xenograft models, potentially through ROS elevation and p53-mediated activation of the intrinsic apoptotic pathway.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"498 ","pages":"Article 117296"},"PeriodicalIF":3.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630820","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 “PPAR gamma agonist, pioglitazone, rescues liver damage induced by renal ischemia/reperfusion injury” [Toxicology and Applied Pharmacology, 362 (2019) 86–94]","authors":"Eman Soliman,&nbsp;Shimaa Mustafa Elshazly","doi":"10.1016/j.taap.2025.117302","DOIUrl":"10.1016/j.taap.2025.117302","url":null,"abstract":"","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"498 ","pages":"Article 117302"},"PeriodicalIF":3.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tryptanthrin alleviate lung fibrosis via suppression of MAPK/NF-κB and TGF-β1/SMAD signaling pathways in vitro and in vivo","authors":"Min Niu ,&nbsp;Yong-Zhi Wang ,&nbsp;Xiang-min Deng ,&nbsp;Xin Wu ,&nbsp;Zheng-Ying Hua ,&nbsp;Ting-Ting Lv","doi":"10.1016/j.taap.2025.117285","DOIUrl":"10.1016/j.taap.2025.117285","url":null,"abstract":"<div><div>Idiopathic pulmonary fibrosis (IPF), a progressive interstitial lung disease of unknown etiology, remains a therapeutic challenge with limited treatment options. This study investigates the therapeutic potential and molecular mechanisms of Tryptanthrin, a bioactive indole quinazoline alkaloid derived from <em>Isatis tinctoria</em> L., in pulmonary fibrosis. In a bleomycin-induced murine IPF model, Tryptanthrin administration (5 and 10 mg/kg/day for 28 days) significantly improved pulmonary function parameters and attenuated histological evidence of fibrosis. Mechanistic analysis revealed dual pathway modulation: Tryptanthrin suppressed MAPK/NF-κB signaling through inhibition of phosphorylation events, subsequently reducing pulmonary levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). Concurrently, it attenuated TGF-β1/Smad pathway activation by decreasing TGF-β1 expression and Smad2/3 phosphorylation, thereby downregulating fibrotic markers including COL1A1, α-smooth muscle actin (α-SMA), and fibronectin in lung tissues. Complementary in vitro studies using Lipopolysaccharide (<em>LPS</em>) or TGF-β1-stimulated NIH3T3 fibroblasts confirmed these anti-inflammatory and anti-fibrotic effects through analogous pathway inhibition. Our findings demonstrate that Tryptanthrin exerts therapeutic effects against pulmonary fibrosis via coordinated modulation of both inflammatory (MAPK/NF-κB) and fibrotic (TGF-β1/Smad) signaling cascades, suggesting its potential as a novel multi-target therapeutic agent for IPF management.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"498 ","pages":"Article 117285"},"PeriodicalIF":3.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634676","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":"Behavioral and endocrine effects of early-life exposure to etonogestrel in zebrafish","authors":"Amanda Carolina Cole Varela ,&nbsp;Lisiane Siqueira ,&nbsp;Milena Fortuna ,&nbsp;Suelen Mendonça Soares ,&nbsp;Natália Freddo ,&nbsp;Ísis Piasson Barletto ,&nbsp;Maíra Souza Ariotti ,&nbsp;Milena Zanoello Bertuol ,&nbsp;Gabriéla Witkowski Rutikoski ,&nbsp;Cecília Mazutti Andrade ,&nbsp;Leonardo José Gil Barcellos","doi":"10.1016/j.taap.2025.117300","DOIUrl":"10.1016/j.taap.2025.117300","url":null,"abstract":"<div><div>Progestin use as a contraceptive has increased exponentially in the last few decades, as has its disposal in the environment. These synthetic hormones can impair the physiology and behavior of non-target organisms, such as fish. In this study, we evaluated the effects of exposure to an environmentally relevant concentration of etonogestrel (ETO, 3.2 ng L⁻¹) on the behavior and endocrine system of zebrafish (<em>Danio rerio</em>) larvae. We found that ETO caused anxiogenic-like behavior in larvae, as demonstrated by the open-field and light-dark tests. The exposed larvae also presented an increase in whole-body cortisol levels. These changes may lead to an ecological imbalance, emphasizing the risk of early exposure to progestins in the environment.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"498 ","pages":"Article 117300"},"PeriodicalIF":3.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629086","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":"Proline betaine facilitates angiogenesis in bronchopulmonary dysplasia","authors":"Wangdui Cili,&nbsp;Zhiye Qi,&nbsp;Qinghua Zhong,&nbsp;Yin Li,&nbsp;Xia Huang,&nbsp;Ruoting Yang,&nbsp;Si Tang,&nbsp;Qingyuan Li,&nbsp;Li Yang,&nbsp;Yue Ning,&nbsp;Yunbo Xie,&nbsp;Yanli Feng,&nbsp;Jiang Duan","doi":"10.1016/j.taap.2025.117301","DOIUrl":"10.1016/j.taap.2025.117301","url":null,"abstract":"<div><h3>Background</h3><div>Bronchopulmonary dysplasia (BPD) is prevalent and severe diseases in preterm infants, characterized by abnormal lung development. This study aims to investigate the therapeutic potential of proline betaine, a natural alkaloid recognized for its vasculo-protective and anti-inflammatory properties, in BPD model.</div></div><div><h3>Methods</h3><div>Network pharmacology was utilized to predict the targets of proline betaine and BPD-related genes (BPD-RGs). In vitro, HUVECs were treated with proline betaine to evaluate its effects on proliferation and angiogenesis. In vivo, a hyperoxia-induced BPD rat model (85 % oxygen, first day to 14th day) was used to evaluate the effects of proline betaine on pulmonary injury, angiogenesis and fibrosis.</div></div><div><h3>Results</h3><div>We identified a total of 100 proline-betaine targets and 825 BPD-RGs, with 20 shared targets between them. These shared targets modulated inflammation, immune response, hypoxia, and vascular homeostasis, especially the vascular phenotype. In vitro<em>,</em> proline betaine significantly enhanced the activity, number of tubes, and capillary length of HUVECs. The pro-angiogenic effect of proline betaine on HUVECs was dose-dependent. The hyperoxia-induced BPD rat model corroborated these findings. In vivo, proline betaine increased the radial alveolar count and reduced the mean linear intercept and collagen content in the lung. Mechanistically, proline betaine upregulated VEGF and VEGFR2 expression as well as MEK/ERK pathway activity. Notably, blocking the VEGFR2 and MEK/ERK pathways made proline betaine less effective as a medicine.</div></div><div><h3>Conclusion</h3><div>Proline betaine enhances angiogenesis and mitigates pulmonary injury through the MEK/ERK pathway. These findings suggest that proline betaine could serve as a novel therapeutic strategy for managing BPD in neonates.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"498 ","pages":"Article 117301"},"PeriodicalIF":3.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634666","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":"Involvement of GSK-3β, NF-κB, PPARγ, and apoptosis in amlodipine's anticancer effect in BALB/c mice","authors":"El-Shaimaa A. Arafa ,&nbsp;Maha M. Abdel-Fattah ,&nbsp;Emad H.M. Hassanein ,&nbsp;Manal A. Buabeid ,&nbsp;Wafaa R. Mohamed","doi":"10.1016/j.taap.2025.117298","DOIUrl":"10.1016/j.taap.2025.117298","url":null,"abstract":"<div><div>Lung cancer is the primary cause of death due to cancer all over the world despite the decrease in the mortality rates from cancer in general. While chemotherapy is a commonly employed treatment for lung cancer, its efficacy is limited due to poor tissue selectivity, inadequate delivery to tumor sites, and associated side effects. The present work aims to assess the potential anti-cancer effectiveness of amlodipine, a calcium channel blocker, on murine lung cancer via modulating GSK-3β, NF-κB, PPARγ, and apoptosis. Lung cancer was induced in BALB/c mice by intraperitoneal injection of 1.5 g/kg in two doses of urethane: once on the 1st and the second on the 60th day of the experiment. Amlodipine was administered orally at a dose of 10 mg/kg/day for the last 28 days of experiment. Relative to urethane group, amlodipine mitigated urethane-induced histopathological abnormalities. It restored oxidant/antioxidant balance by normalizing MDA, GSH, and SOD. Furthermore, it exerted a marked anti-inflammatory effect through downregulating lung MPO, ICAM-1, IL-6, TNF-α, and NF-қB expressions. Amlodipine enhanced apoptosis of cancer cells as evidenced by increasing Bax and decreasing Bcl-2 expression. The anticancer effect of amlodipine was suggested to be mediated through increasing PPARγ and reducing GSK3β and <em>p</em>-GSK3β signaling. Collectively, these results suggest that amlodipine could exert a promising anticancer effect against lung cancer through modulating GSK-3β, NF-κB, PPARγ, and apoptosis. Our findings could be highly significant in clinical settings, offering a valuable adjuvant option for managing lung carcinoma, particularly in patients with cardiovascular disorders.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"498 ","pages":"Article 117298"},"PeriodicalIF":3.3,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634659","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":"Arsenic and metabolic diseases: New insights from mesenchymal stem cells","authors":"Yuxin Hu ,&nbsp;Jialin He ,&nbsp;Yue Ma ,&nbsp;Lili Ge ,&nbsp;Bin Lou ,&nbsp;Xin Fang ,&nbsp;Huihui Wang ,&nbsp;Yuanyuan Xu","doi":"10.1016/j.taap.2025.117299","DOIUrl":"10.1016/j.taap.2025.117299","url":null,"abstract":"<div><div>Arsenic is a common toxic metal contaminant in the environment. Humans are exposed to arsenic through drinking water, air, food, and medical treatment. Chronic exposure to arsenic is a well-documented risk factor of type 2 diabetes and a potential risk factor of osteoporosis and obesity. Mesenchymal stem cells (MSCs) are adult stem cells with multiple differentiation potential and immunomodulatory capacity. These cells have shown therapeutic potential in experimental studies of metabolic diseases by differentiating into parenchymal cells of damaged tissues, such as islet-like cells and osteoblasts, and resisting chronic inflammation. Meanwhile, when key functional genes were suppressed in MSCs, experimental animals showed metabolic disease-related changes, such as insulin resistance and obesity. Arsenic exposure inhibits the differentiation capacity of MSCs, leads to changes in the synthesis and secretion of immunomodulatory factors, and induces cellular senescence and apoptosis. Therefore, dysfunction and death of MSCs may be important pathogenesis of arsenic-related metabolic diseases. Future studies on the functional changes of MSCs in arsenic-related metabolic diseases and the role of MSCs in arsenic pathogenesis are worthwhile. In addition, the mechanism of arsenic-induced dysfunction in MSCs needs to be explored in depth.</div></div>","PeriodicalId":23174,"journal":{"name":"Toxicology and applied pharmacology","volume":"498 ","pages":"Article 117299"},"PeriodicalIF":3.3,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143626115","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}