Toxicology in Vitro最新文献_第5页

Marked differences in thyroxine (T4) metabolism following in vitro exposure of Wistar rat and human hepatocytes to several reference CAR/PXR nuclear receptor activators Wistar大鼠和人肝细胞体外暴露于几种参考CAR/PXR核受体激活剂后甲状腺素（T4）代谢的显著差异

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-02-03 DOI: 10.1016/j.tiv.2025.106016

Audrey Baze , Betty Ory , Liliia Horbal , Helen Tinwell , Lysiane Richert

{"title":"Marked differences in thyroxine (T4) metabolism following in vitro exposure of Wistar rat and human hepatocytes to several reference CAR/PXR nuclear receptor activators","authors":"Audrey Baze , Betty Ory , Liliia Horbal , Helen Tinwell , Lysiane Richert","doi":"10.1016/j.tiv.2025.106016","DOIUrl":"10.1016/j.tiv.2025.106016","url":null,"abstract":"<div><div>Our study builds upon previous findings (<span><span>Baze et al., 2024</span></span>) by investigating species differences in thyroxine (T4) metabolism regulation by CAR/PXR activators using cryopreserved primary Wistar rat hepatocytes (PRH) and human hepatocytes (PHH) in 2D-sandwich over a 7-day treatment period. Daily exposure of PRH to phenobarbital, 5-Pregnen-3β-ol-20-one-16α‑carbonitrile (PCN) or dexamethasone increased T4 clearance over the last 24 h exposure (up to 60 %, 79 % and 67 % over control, respectively) and secretion of T4-glucuronide (T4-G; up to 463, 661 and 545 pmol/10<sup>6</sup> cells over control, respectively). Effects were concentration-dependent for phenobarbital and PCN and highest at the lowest concentration for dexamethasone, while rifampicin barely affected T4 clearance and T4-G secretion. None of the compounds, at any tested concentration, affected these parameters in PHH. Additionally, mRNA expression data were consistent with the species-specific and concentration-dependent regulation of phase I <em>Cyp/CYP</em>, phase II <em>Ugt/UGT</em> and phase III <em>Mrp2/MRP2</em> pathways occurring in rat and human liver following CAR/PXR activation. T4-UGT relative activity increased in PRH only, specifically by PCN, dexamethasone and phenobarbital. The comparison of PRH and PHH responses to compounds represents an important step towards using <em>in vitro</em> methods to reduce animal testing. We recommend using relative T4-UGT activity thresholds observed in PRH as benchmarks for defining compound-related effects across species, helping determine the human relevance of thyroid effects in rodents.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"104 ","pages":"Article 106016"},"PeriodicalIF":2.6,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256685","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}

引用次数: 0

Transcriptomic changes and mitochondrial toxicity in response to acute and repeat dose treatment with brequinar in human liver and kidney in vitro models 体外模型人类肝脏和肾脏对布雷奎那急性和重复剂量治疗的转录组变化和线粒体毒性反应

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-02-01 DOI: 10.1016/j.tiv.2025.106010

Tamara Meijer , Bas ter Braak , Liesanne Loonstra-Wolters , Steven J. Kunnen , Barira Islam , Ilinca Suciu , Iain Gardner , Oliver Hatley , Richard Currie , Barry Hardy , Marcel Leist , Bob van de Water , Paul Jennings , Anja Wilmes

{"title":"Transcriptomic changes and mitochondrial toxicity in response to acute and repeat dose treatment with brequinar in human liver and kidney in vitro models","authors":"Tamara Meijer , Bas ter Braak , Liesanne Loonstra-Wolters , Steven J. Kunnen , Barira Islam , Ilinca Suciu , Iain Gardner , Oliver Hatley , Richard Currie , Barry Hardy , Marcel Leist , Bob van de Water , Paul Jennings , Anja Wilmes","doi":"10.1016/j.tiv.2025.106010","DOIUrl":"10.1016/j.tiv.2025.106010","url":null,"abstract":"<div><div>The potent dihydroorotate dehydrogenase (DHODH) inhibitor brequinar has been investigated as an anticancer, immunosuppressive, and antiviral pharmaceutical agent. However, its toxicity is still poorly understood. We investigated the cellular responses of primary human hepatocytes (PHH) and telomerase-immortalised human renal proximal tubular epithelial cells (RPTEC/TERT1) after a single 24-h exposure up to 100 μM brequinar. Additionally, RPTEC/TERT1 cells underwent repeated daily exposure for five consecutive days at 0.3, 3, and 20 μM. Transcriptomic analysis revealed that PHH were less sensitive to brequinar treatment than RPTEC/TERT1 cells. Upregulation of various phase I and II drug-metabolising enzymes, particularly Cytochrome P450 (CYP) 1 A and 3 A enzymes, in PHH suggests potential detoxification. Furthermore, brequinar exposure led to a significant upregulation of several stress response pathways in PHH and RPTEC/TERT1 cells, including the unfolded protein response, Nrf2, p53, and inflammatory responses. RPTEC/TERT1 cells exhibited greater sensitivity to brequinar at 0.3 μM with repeated exposure compared to a single exposure. Furthermore, brequinar could impair the mitochondrial respiration of RPTEC/TERT1 cells after 24 h. This study provides new insights into the differential responses of PHH and RPTEC/TERT1 cells in response to brequinar exposure and highlights the biological relevance of implementing repeated dosing regimens in in vitro studies.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"104 ","pages":"Article 106010"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123978","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}

引用次数: 0

The effects of flavored vaped e-liquids on cultured human macrophages derived from the central and peripheral nervous systems 调味电子烟液体对培养的来自中枢和周围神经系统的人巨噬细胞的影响。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-01-31 DOI: 10.1016/j.tiv.2025.106013

Ciani C. Bradley , Imari Walker-Franklin , Alex Kovach , Vijay Sivaraman , Rob U. Onyenwoke

{"title":"The effects of flavored vaped e-liquids on cultured human macrophages derived from the central and peripheral nervous systems","authors":"Ciani C. Bradley , Imari Walker-Franklin , Alex Kovach , Vijay Sivaraman , Rob U. Onyenwoke","doi":"10.1016/j.tiv.2025.106013","DOIUrl":"10.1016/j.tiv.2025.106013","url":null,"abstract":"<div><div>The use of the electronic cigarette (e-cig) to consume an aerosol is referred to as “vaping” and has become the most popular method for nicotine consumption amongst youth and many adults worldwide. This popularity is at least partially attributable to the availability of 1000s of distinctly flavored e-liquids. At present, a large number of studies have evaluated the potential negative effects of e-cig use in relation to pulmonary disease. These studies have demonstrated that vaping can lead to immune activation and cell death but typically include only epithelial cell line studies. At present, significantly less is known about the effects of vaped e-liquids on the central nervous system (CNS) and peripheral nervous system (PNS). To investigate this gap, we utilized the human macrophage cell lines KG-1 (PNS-resident macrophages) and DBTRG-05MG (CNS-resident macrophages) and examined their exposure to vaped e-liquids. To carry out these investigations, measurements of: cell viability, expression of inflammatory cytokines, phagocytosis and reactive oxygen species (ROS) were employed. Our findings illustrate that when exposed to e-liquid, and especially flavored e-liquids, both peripheral and central macrophage cell lines decrease in cell viability, showcase an upregulated level of expression of pro-inflammatory cytokines, a diminished level of phagocytic activity and an overall increased level of reactive oxidative species. Thus, our study further indicates that the use of the e-cig can cause phenotype and immune disruptions within both the CNS and PNS.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"104 ","pages":"Article 106013"},"PeriodicalIF":2.6,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080838","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}

引用次数: 0

Predicting the skin sensitizing potential of pesticides using Pred-skin 3.0–A web-based prediction tool 使用Pred-skin 3.0-A网络预测工具预测农药的皮肤致敏潜力。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-01-30 DOI: 10.1016/j.tiv.2025.106015

Ajay Godwin Potnuri , Lingesh Allakonda , Ajith Kakaraparthi

{"title":"Predicting the skin sensitizing potential of pesticides using Pred-skin 3.0–A web-based prediction tool","authors":"Ajay Godwin Potnuri , Lingesh Allakonda , Ajith Kakaraparthi","doi":"10.1016/j.tiv.2025.106015","DOIUrl":"10.1016/j.tiv.2025.106015","url":null,"abstract":"<div><div>Pesticide usage is increasing due to growing needs of agriculture and horticulture. Occupational dermal exposure to pesticides at an acute or chronic low-level could result in contact dermatitis and various skin cancers. Hence, detailed understanding about the Adverse Outcome Pathways (AOP) or Chemical Sensitization Pathway (CSP) behind pesticides belonging to various categories has to be investigated. Animal models of skin sensitization testing at times either over or under predict the human responses due to species-to-species variability. This necessitates the need for prediction tools for skin sensitizing potential of various chemicals. Pred-skin 3.0, is a consensus Naïve Bayes model-based prediction tool which utilizes various human, LLNA, and non-animal data to predict skin sensitization. Although, this tool was never used for predicting skin sensitizing potential of pesticides. Henceforth, the current study aims to test the applicability of this prediction tool in predicting skin sensitizing potential of 96 pesticides belonging to three Major classes. The Bayesian outcome of Pred Skin prediction tool provided a good concordance of 72.72 % with the existing animal skin sensitizing data as well as 63.46 % with the non-sensitizer data.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"104 ","pages":"Article 106015"},"PeriodicalIF":2.6,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076354","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}

引用次数: 0

TCDD inhibits the proliferation of C17.2 cells through the activation of the c-Cbl/β-catenin signaling pathway TCDD通过激活c-Cbl/β-catenin信号通路抑制C17.2细胞的增殖。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-01-27 DOI: 10.1016/j.tiv.2025.106014

Yewen Cong , Yue Wu , Yue Liu , Yongjun Ai , Xiping Wang , Chunxi Wei , Haoyu Ding , Guangfei Xu , Wenxing Sun

{"title":"TCDD inhibits the proliferation of C17.2 cells through the activation of the c-Cbl/β-catenin signaling pathway","authors":"Yewen Cong , Yue Wu , Yue Liu , Yongjun Ai , Xiping Wang , Chunxi Wei , Haoyu Ding , Guangfei Xu , Wenxing Sun","doi":"10.1016/j.tiv.2025.106014","DOIUrl":"10.1016/j.tiv.2025.106014","url":null,"abstract":"<div><div>2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD) belongs to the category of persistent environmental pollutants, and gestational exposure to TCDD can lead to cognitive, memory, and motor deficits, as well as altered neuron development in rodents. However, the molecular mechanisms underlying TCDD's neurotoxicity remain unclear. Neural stem cells (NSCs) possess the capacity for self-renewal and can generate various cell types within the brain, playing fundamental roles in brain development and regeneration. This study investigated the impact of TCDD on the proliferation of mouse NSCs, specifically focusing on the C17.2 cell line. The results demonstrated that TCDD inhibited the proliferation of C17.2 cells in a dose-dependent manner. Even low doses of TCDD (5 nM) significantly reduced C17.2 cell proliferation. Regarding the molecular mechanisms, it was found that TCDD induced the degradation of β-catenin, a key regulator of cell proliferation, through the upregulation of the E3 ubiquitin ligase, casitas B-lineage lymphoma (c-Cbl), which was dependent on the aryl-hydrocarbon Receptor (AhR). Furthermore, knockdown of c-Cbl alleviated the TCDD-induced inhibition of C17.2 proliferation and of the reduction of β-catenin expression. Our research provides foundational data to understand the mechanism of TCDD-induced neurotoxicity through the inhibition of NSCs proliferation, and suggests that the c-cbl/β-catenin pathway may serve as a potential therapeutic target for countering the neurotoxicants of TCDD.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"104 ","pages":"Article 106014"},"PeriodicalIF":2.6,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069767","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}

引用次数: 0

Sex steroid disrupting effects of nonsteroidal anti-inflammatory drugs on the Persian Gulf Arabian Sea bream, Acanthopagrus arabicus: In vitro model of environmental drug contamination 非甾体抗炎药对波斯湾阿拉伯海鲷的性类固醇干扰作用：环境药物污染的体外模型。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-01-24 DOI: 10.1016/j.tiv.2025.106008

Zahra Beitgader , Negin Salamat , Mohammad Ali Salarialiabadi , Hoda Mojiri-Forushani , Asma Mohammadi

{"title":"Sex steroid disrupting effects of nonsteroidal anti-inflammatory drugs on the Persian Gulf Arabian Sea bream, Acanthopagrus arabicus: In vitro model of environmental drug contamination","authors":"Zahra Beitgader , Negin Salamat , Mohammad Ali Salarialiabadi , Hoda Mojiri-Forushani , Asma Mohammadi","doi":"10.1016/j.tiv.2025.106008","DOIUrl":"10.1016/j.tiv.2025.106008","url":null,"abstract":"<div><div>The presence of pharmaceuticals in aquatic ecosystems and their impact on humans and the environment are growing concerns in environmental health. This study aimed to evaluate the potential reproductive effects of diclofenac, ibuprofen, and aspirin on dissociated ovarian and testicular cells from Arabian Sea bream, <em>Acanthopagrus arabicus</em>. The cells were exposed to varying concentrations of the pharmaceuticals for 48 h. Steroid (17-β-estradiol (E2) and 11-ketotestosterone (11-KT)) production by the cells was assessed at 0, 12, 24, and 48 h of the experiment. The findings showed that diclofenac did not impact the production of E2 and 11-KT by ovarian cells, but it did significantly decrease the secretion of 11-KT from testicular cells. Ibuprofen and aspirin, on the other hand, both increased the production of the studied steroid hormones by ovarian cells and reduced the secretion of 11-KT by testicular cells in a dose- and time-dependent manner. The pharmaceuticals studied were potent inhibitors of 11-KT secretion, particularly at higher concentrations in the cultured testicular cells. However, they were also found to stimulate steroid production from fish ovarian cells. In conclusion, the results suggest that analgesics (diclofenac, ibuprofen, and aspirin) have the potential to disrupt estrogen biosynthesis and impact reproduction in fish.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"104 ","pages":"Article 106008"},"PeriodicalIF":2.6,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048711","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}

引用次数: 0

Risk assessment of chlorophenols (CPs) exposure in vitro:Inhibition of sulfotransferases (SULTs) activity 氯酚（CPs）体外暴露的风险评估：硫转移酶（SULTs）活性的抑制。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-01-23 DOI: 10.1016/j.tiv.2025.106012

Kai Yang , Guo-Qiang Qin , Zi-Zhuo Jia , Qiangqiang Gan , Ruo-Yong Jia , Wei Zhang , Yong-Zhe Liu , Zhong-Ze Fang

{"title":"Risk assessment of chlorophenols (CPs) exposure in vitro:Inhibition of sulfotransferases (SULTs) activity","authors":"Kai Yang , Guo-Qiang Qin , Zi-Zhuo Jia , Qiangqiang Gan , Ruo-Yong Jia , Wei Zhang , Yong-Zhe Liu , Zhong-Ze Fang","doi":"10.1016/j.tiv.2025.106012","DOIUrl":"10.1016/j.tiv.2025.106012","url":null,"abstract":"<div><div>Chlorophenols (CPs) are common organic pollutants widely used in many industries. The current study seeks to examine the inhibition of sulfotransferases (SULTs) by CPs. Four SULT isoforms were significantly inhibited by multiply CPs. Furthermore, half inhibition concentration (IC<sub>50</sub>) was calculated to be 0.31 μM, 0.11 μM and 1.86 μM for the inhibition of PCP (pentachlorophenol) towards SULT1A1, SULT1B1 and SULT1E1. PCP showed competitive inhibition towards SULT1B1 and SULT1E1.The inhibition kinetics (inhibition type and parameters (K<sub>i</sub>)) values were calculated to be 0.34 μM and 0.56 μM for the inhibition of PCP towards SULT1B1 and SULT1E1, respectively. <em>In silico</em> docking was used to explain the inhibition difference among CPs. The binding free energy between 4-CP and SULT1A3 was −4.92 kcal/mol, and the binding free energy between 2.4-DCP and SULT1A3 was −5.63 kcal/mol. Therefore, 2.4-DCP exerted stronger inhibition activity towards SULT1A3 compared with 4-CP, which can well explain the experimental result. These results are crucial for exploring the risks associated with CPs exposure from a novel perspective.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"104 ","pages":"Article 106012"},"PeriodicalIF":2.6,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043342","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}

引用次数: 0

Studying the intracellular bile acid concentration and toxicity in drug-induced cholestasis: Comprehensive LC-MS/MS analysis with human liver slices 药物性胆汁淤积症细胞内胆汁酸浓度及毒性研究：人肝片LC-MS/MS综合分析

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-01-22 DOI: 10.1016/j.tiv.2025.106011

R.E.H. Karsten , K. Gier , V.E. de Meijer , W.H.C. Huibers , H.P. Permentier , E. Verpoorte , P. Olinga

{"title":"Studying the intracellular bile acid concentration and toxicity in drug-induced cholestasis: Comprehensive LC-MS/MS analysis with human liver slices","authors":"R.E.H. Karsten , K. Gier , V.E. de Meijer , W.H.C. Huibers , H.P. Permentier , E. Verpoorte , P. Olinga","doi":"10.1016/j.tiv.2025.106011","DOIUrl":"10.1016/j.tiv.2025.106011","url":null,"abstract":"<div><div>Drug-induced cholestasis (DIC) is a leading cause of drug-induced liver injury post-drug marketing, characterized by bile flow obstruction and toxic bile constituent accumulation within hepatocytes. This study investigates the toxicity associated with intracellular bile acid (BA) accumulation during DIC development. Using liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis, we examined intracellular BA concentrations in human precision-cut liver slices (PCLS) following the administration of cyclosporin A and chlorpromazine, both with and without an established BA mixture.</div><div>Our findings indicate toxicity of cyclosporin A upon BA addition, while chlorpromazine's toxicity remained unaffected. Although neither drug led to the accumulation of all BAs intracellularly, BA mixture addition resulted in the accumulation of unconjugated BAs associated with DIC, such as deoxycholic acid (DCA) and cholic acid (CA). Additionally, cyclosporin A increased taurolithocholic acid (TLCA) concentrations. In the absence of the BA mixture, a decrease in conjugated BAs was observed, suggesting inhibition of BA metabolism by cholestatic drugs and warranting further investigation. The evident increase in CA and DCA for both drugs (and TLCA for cyclosporin A), despite not exacerbating toxicity with chlorpromazine, suggests these increases may be related to DIC development and possible toxicity.</div><div>In conclusion, the current human PCLS model is appropriate for investigating and detecting essential contributors to DIC and can be used in future studies elucidating DIC <em>ex vivo</em>.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"104 ","pages":"Article 106011"},"PeriodicalIF":2.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143043344","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}

引用次数: 0

The obesogenic effects of Bisphenol A and its analogues are differentially regulated via PPARγ transactivation in mouse 3T3-L1 cells 在小鼠3T3-L1细胞中，双酚A及其类似物的致肥作用通过PPARγ转激活受到差异调节。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-01-20 DOI: 10.1016/j.tiv.2025.106009

Jennifer Crosthwait , Syed Syeddan , Ella Atlas

{"title":"The obesogenic effects of Bisphenol A and its analogues are differentially regulated via PPARγ transactivation in mouse 3T3-L1 cells","authors":"Jennifer Crosthwait , Syed Syeddan , Ella Atlas","doi":"10.1016/j.tiv.2025.106009","DOIUrl":"10.1016/j.tiv.2025.106009","url":null,"abstract":"<div><div>Exposure to environmental pollutants with obesogenic activity is being recognised as one of the contributing factors to the obesity epidemic. Bisphenol A (BPA) has been shown to stimulate adipogenesis in both human and mouse preadipocytes, to increase body weight and affect lipid metabolism in animal and epidemiological studies. Regulatory action and public concern has prompted industry to replace BPA with other structurally similar analogues that may have similar effects.</div><div>In this study we investigated the effects of fifteen BPA analogues on adipogenesis in the mouse 3 T3-L1 pre-adipocyte cell model in order to determine their adipogenic activity relative to BPA. 3 T3-L1 cells were treated with increasing concentrations of BPA and replacements and mRNA expression of the mature adipocyte markers fatty acid binding protein 4 (<em>Fabp4</em>), perilipin (<em>Plin</em>) lipoprotein lipase (<em>Lpl)</em>and peroxisome proliferator-activated receptor (<em>Ppar</em>)γ and lipid accumulation were assessed. In addition, a luciferase reporter assay for PPARγ transactivation was employed to investigate mechanism of action.</div><div>Our results show that BPC, BPS-MAE, BPS-MPE and TGSA, were the most adipogenic bisphenols, as shown by a robust increase in lipid accumulation and mRNA expression of adipogenic markers. BPS-MPE, BPC, BTUM, TGSA and D8 increased PPARγ transcriptional activity. Despite its ability to activate PPARγ in the transcriptional assay D8 did not affect adipogenesis in this cell model.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"104 ","pages":"Article 106009"},"PeriodicalIF":2.6,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025684","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}

引用次数: 0

DTPA and anti-inflammatory drug associations to alleviate Pu-induced response of macrophages in vitro DTPA与抗炎药物联合减轻巨噬细胞pu诱导的体外反应。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-01-19 DOI: 10.1016/j.tiv.2025.106007

Alexandra Bourgois , Guillaume Cosler , Diane Riccobono , Clélia Le Gallic , Sabine François , Anne Van der Meeren

{"title":"DTPA and anti-inflammatory drug associations to alleviate Pu-induced response of macrophages in vitro","authors":"Alexandra Bourgois , Guillaume Cosler , Diane Riccobono , Clélia Le Gallic , Sabine François , Anne Van der Meeren","doi":"10.1016/j.tiv.2025.106007","DOIUrl":"10.1016/j.tiv.2025.106007","url":null,"abstract":"<div><div>Internal contamination by inhalation of plutonium poorly soluble compounds leads to their long time retention in alveolar macrophages inducing delayed pathology development. As previous studies highlighted co-localization of retained Pu and inflammatory lesions, this study was designed to assess the combined effect of the reference treatment (DTPA) and anti-inflammatory drugs on Pu-induced early response of macrophages in vitro.</div><div>Pu colloids, mimicking poorly soluble Pu, were characterized using filtration and solid-state nuclear track detectors CR39. Their bioavailability was determined using a biphasic acellular model. Treatment effects on Pu dissolution and release as well as on Pu-induced pro-inflammatory response were assessed over 7 days on macrophage-like cells.</div><div>DTPA treatment, associated or not with anti-inflammatory drug, increased Pu dissolution and release from contaminated THP-1 differentiated cells after 7 days. Significant decreases in Pu-induced IL-8 and MCP-1 secretions were also observed with anti-inflammatory treatment associated or not with DTPA.</div><div>This study highlighted the ability of DTPA to partially dissolve a poorly soluble form of Pu as well as the ability of anti-inflammatory drugs to modulate Pu-induced pro-inflammatory response in macrophage-like cells. These treatments seem a promising strategy to improve the clinical management of Pu pulmonary contaminations and to limit delayed pulmonary pathology occurrence.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"104 ","pages":"Article 106007"},"PeriodicalIF":2.6,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016610","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}

引用次数: 0