Toxicology in Vitro最新文献_第2页

Cadmium sulfide nanoparticles (CdSNPs) modulate key oncogenic pathways in PA1 ovarian cancer cells: Insights from transcriptomic analysis 硫化镉纳米颗粒（CdSNPs）调节PA1卵巢癌细胞的关键致癌途径：来自转录组学分析的见解

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-05-13 DOI: 10.1016/j.tiv.2025.106079

Aditi Bhatnagar , Abhay Dev Tripathi , Sonali Kumari, Abha Mishra

{"title":"Cadmium sulfide nanoparticles (CdSNPs) modulate key oncogenic pathways in PA1 ovarian cancer cells: Insights from transcriptomic analysis","authors":"Aditi Bhatnagar , Abhay Dev Tripathi , Sonali Kumari, Abha Mishra","doi":"10.1016/j.tiv.2025.106079","DOIUrl":"10.1016/j.tiv.2025.106079","url":null,"abstract":"<div><div>Transcriptomics has become a useful tool for comparing the levels of gene expression in healthy and malignant cells, holding potential for the discovery of new cancer therapies. This study used RNA-sequencing and transcriptome analysis on the PA1 ovarian cancer cell line to examine the potential of Cadmium Sulfide Nanoparticles (CdSNPs) as a therapeutic agent. A total of 5.42 Gb of high-quality reads was estimated based on the findings of gene expression techniques, comprising 2.25 Gb of treated PA1 cells and 3.17 Gb of control cells. Of these, 1641 genes with padj<0.001 and log2 foldchange >2 were found to be significantly regulated DEGs (differentially expressed genes). Analysis of gene ontology (GO) assays demonstrates the molecular mechanism behind CdSNPs anticancer effects. GO:0006915, GO:0012501, GO:1903561, and GO:0070588 are a few significant highlights of elevated GO (enriched DEGs) that are involved in apoptotic pathways, extracellular vesicles, programmed cell death, and Ca++ signaling. KEGG analysis elucidated that up and downregulated DEGs were enriched in a few pathways: calcium signaling pathway, Apoptosis, and TNF signaling pathway. Important pathways like MAP kinase, JAK/STAT, cAMP, and folate biosynthesis, showed inhibitory effects on ovarian cancer cell proliferation. The results of this work provide insight into possible therapeutic approaches employing CdSNPs and encourage additional research using a variety of cell lines and in vivo models to improve ovarian cancer treatment.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"107 ","pages":"Article 106079"},"PeriodicalIF":2.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071508","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

Zinc finger transcription factor ZNF384 mitigates LPS-induced ferroptosis and inflammation in lung epithelial cells by activating SESN2-mediated autophagy 锌指转录因子ZNF384通过激活sesn2介导的自噬，减轻lps诱导的肺上皮细胞铁凋亡和炎症

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-05-13 DOI: 10.1016/j.tiv.2025.106073

Lu Shi , Hongxue Fu , Yingting Hao , Chang Liu , Fachun Zhou

{"title":"Zinc finger transcription factor ZNF384 mitigates LPS-induced ferroptosis and inflammation in lung epithelial cells by activating SESN2-mediated autophagy","authors":"Lu Shi , Hongxue Fu , Yingting Hao , Chang Liu , Fachun Zhou","doi":"10.1016/j.tiv.2025.106073","DOIUrl":"10.1016/j.tiv.2025.106073","url":null,"abstract":"<div><h3>Background</h3><div>Ferroptosis, a type of programmed cell death distinct from apoptosis, is potentially associated with sepsis-triggered acute respiratory distress syndrome (ARDS). ZNF384 is a transcription factor, but its role in ARDS remain unclear.</div></div><div><h3>Methods</h3><div>Blood samples were collected from sepsis-induced ARDS patients and healthy controls. BEAS-2B cells were stimulated with lipopolysaccharide (LPS) to mimic sepsis-induced damaged lung epithelial cell model. Gene and protein expression were elevated utilizing RT-qPCR, western blot, and immunofluorescent staining, respectively. Cell viability and death were evaluated by CCK-8 and flow cytometry. Inflammatory cytokines and oxidative stress markers were measured using ELISA. Intracellular ROS was determined using DCFH-DA staining. Iron concentration was measured using an iron detection kit. Target relationships were confirmed through ChIP and luciferase reporter assays.</div></div><div><h3>Results</h3><div>ZNF384 and SESN2 levels were downregulated in sepsis-induced ARDS patients. Overexpression of ZNF384 reduced inflammatory injury, ferroptosis and enhanced autophagy in LPS-stimulated BEAS-2B cells. Mechanistically, ZNF384 served as transcriptional activator of SESN2 to boost autophagy activation. Rescue experiments validated that depletion of SESN2 strikingly reversed the regulatory function of ZNF384 in LPS-induced inflammation, autophagy and ferroptosis.</div></div><div><h3>Conclusion</h3><div>ZNF384 alleviated LPS-triggered ferroptosis and inflammation in BEAS-2B cells via activating SESN2-mediated autophagy, indicating ZNF384 was a novel target for ARDS treatment.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"107 ","pages":"Article 106073"},"PeriodicalIF":2.6,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071507","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

The Alarming Consequences of Workforce Reductions at the FDA, EPA, NIH and CDC in the United States 美国FDA、EPA、NIH和CDC裁员的惊人后果

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-05-03 DOI: 10.1016/j.tiv.2025.106077

引用次数: 0

Cigarette sidestream smoke-induced cellular senescence and the protective role of histone H2AX 香烟侧流烟雾诱导的细胞衰老及组蛋白H2AX的保护作用

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-04-24 DOI: 10.1016/j.tiv.2025.106076

Yukako Komaki, Yuko Ibuki

{"title":"Cigarette sidestream smoke-induced cellular senescence and the protective role of histone H2AX","authors":"Yukako Komaki, Yuko Ibuki","doi":"10.1016/j.tiv.2025.106076","DOIUrl":"10.1016/j.tiv.2025.106076","url":null,"abstract":"<div><div>Cigarette smoke imposes serious health hazards such as cancer and cardiovascular diseases but is also associated with cellular senescence. Recently, histone loss and modifications are reported as one of the characteristics of cellular senescence. In this study, we examined the relationship between cigarette smoke-induced cellular senescence and histone H2A variant H2AX, an important player in DNA damage response. We exposed normal human skin diploid fibroblast ASF-4-1 to cigarette sidestream smoke (CSS) extract and successfully induced premature senescence. Persistent DNA damages are known to induce cellular senescence. Double strand breaks (DSBs) formation was detected in CSS-treated cells, indicating DSBs could be the cause for the CSS-induced cellular senescence. In the senescent cells, persistent phosphorylation of histone H2AX (γ-H2AX) and unexpected increase of H2AX protein expression was observed. To elucidate the role of H2AX in CSS-induced cellular senescence, we depleted H2AX in ASF-4-1 cells with siRNA. In H2AX-depleted cells, CSS-induced elevated β-galactosidase activity was more prominent. CSS concentration-dependent increase of reactive oxygen species and DSBs formation was also facilitated by H2AX depletion. These results suggest that histone H2AX may have a protective role against DNA damage-induced premature senescence.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"107 ","pages":"Article 106076"},"PeriodicalIF":2.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891621","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

Association between drug-induced heart failure and CYP1A1, CYP1B1, and CYP3A4 inhibition: Utility of cytochrome P450 inhibition assay for evaluating cardiotoxicity of drug candidates 药物性心力衰竭与CYP1A1、CYP1B1和CYP3A4抑制之间的关系：细胞色素P450抑制试验用于评估候选药物的心脏毒性

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-04-19 DOI: 10.1016/j.tiv.2025.106075

Shunnosuke Kaito , Kiyomi Sato , Takamitsu Sasaki , Takuomi Hosaka , Ryota Shizu , Jun-ichi Takeshita , Kouichi Yoshinari

{"title":"Association between drug-induced heart failure and CYP1A1, CYP1B1, and CYP3A4 inhibition: Utility of cytochrome P450 inhibition assay for evaluating cardiotoxicity of drug candidates","authors":"Shunnosuke Kaito , Kiyomi Sato , Takamitsu Sasaki , Takuomi Hosaka , Ryota Shizu , Jun-ichi Takeshita , Kouichi Yoshinari","doi":"10.1016/j.tiv.2025.106075","DOIUrl":"10.1016/j.tiv.2025.106075","url":null,"abstract":"<div><div>Unpredictable adverse drug reactions (ADRs) present a significant challenge in drug development and require advanced prediction systems for ADRs. Previously, we identified a connection between drug-induced liver injury (DILI) and the inhibition of CYP1A1 or CYP1B1, reporting the usefulness of this inhibition data from these cytochrome P450s (P450s) for predicting DILI. This study aimed to investigate the utility of P450 inhibition data in predicting drug-induced organ toxicities beyond DILI. We selected 364 drugs with ADR information as test drugs from the public database SIDER (Side Effect Resource). Our focus was on 10 groups of ADRs affecting the liver, kidney, heart, blood/hematopoietic system, intestines, muscle, and lungs, as classified by MedDRA. The inhibitory activities of 10 human P450s were evaluated in vitro using recombinant enzymes and luminescent substrates. Our analyses revealed notable associations between heart failure and the inhibition of CYP1A1, CYP1B1, and CYP3A4. Heart failure-positive drugs tended to exhibit strong inhibition of these P450s compared to heart failure-negative drugs. Furthermore, most drugs that inhibited two or three of the three P450 forms were found to be heart failure-positive. These results suggest that the inhibition assay data for CYP1A1, CYP1B1, and CYP3A4 help assess drug-induced cardiotoxicity during drug development.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"107 ","pages":"Article 106075"},"PeriodicalIF":2.6,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869489","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

A549 cells exposed to a marijuana smoke extract affect mono-layer integrity related to oxidative stress state 暴露于大麻烟雾提取物的A549细胞影响与氧化应激状态相关的单层完整性

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-04-16 DOI: 10.1016/j.tiv.2025.106072

Elvira Gómez-Guerrero , Yazmín Debray-García , Octavio Gamaliel Aztatzi-Aguilar , Fanny Azuzena Colchero-Amateco , Omar Amador-Muñoz , Josefina Poblano-Bata , Irais Poblete-Naredo , Arnulfo Albores

{"title":"A549 cells exposed to a marijuana smoke extract affect mono-layer integrity related to oxidative stress state","authors":"Elvira Gómez-Guerrero , Yazmín Debray-García , Octavio Gamaliel Aztatzi-Aguilar , Fanny Azuzena Colchero-Amateco , Omar Amador-Muñoz , Josefina Poblano-Bata , Irais Poblete-Naredo , Arnulfo Albores","doi":"10.1016/j.tiv.2025.106072","DOIUrl":"10.1016/j.tiv.2025.106072","url":null,"abstract":"<div><div>Marijuana smoke contains several toxic compounds that may induce dysregulation of oxidative mechanisms and barrier system in airway alveolar cells. This study aimed to assess whether marijuana smoke extract (MSE) modifies mono-layer integrity and antioxidant effects on the alveolar epithelial cells. A549 cells were exposed to MSE (0.1 to 5 μg/mL) or cannabinoid (+)-WIN 55,212–2 (WIN; 0.01 to 1 μM) for 24 h. Epithelial integrity and protein expression of claudin (Cl)-2, Cl-5, and occludin (Ocl) were evaluated by transepithelial electrical resistance (TEER), permeability assay, Western blot, immunofluorescence, and qPCR. TEER decreased after MSE or WIN exposure, whereas the monolayer permeability increased. Protein expression and localization of Cl-2 and Ocl were reduced after MSE treatment. However, WIN increased Cl-2 protein and decreased Cl-5 and Ocl. Differential gene expressions were observed between treatments. Malondialdehyde (MDA) production and advanced oxidation protein products (AOPP) determination showed that MSE increased AOPP, whereas WIN augmented the MDA production and decreased AOPP levels. The activity of antioxidant enzymes shows an increase in catalase, glutathione-<em>S</em>-transferase, γ-glutamyl transferase and arginase after MSE treatment and a decrease with WIN. Data indicates that MSE exposure alters epithelial integrity and the alveolar cells antioxidant response that, finally, may lead to lung damage.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"107 ","pages":"Article 106072"},"PeriodicalIF":2.6,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874686","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

Effects of Penthorum chinense pursh and gallic acid on embryonic and cardiac development in zebrafish (Danio rerio) 五倍子提取物和没食子酸对斑马鱼胚胎和心脏发育的影响

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-04-15 DOI: 10.1016/j.tiv.2025.106074

Kehui Liu , Hui Jiang , Rong Ji , Yuanyuan Ma , Rui Zhang , Binbin Song , Ying Han

{"title":"Effects of Penthorum chinense pursh and gallic acid on embryonic and cardiac development in zebrafish (Danio rerio)","authors":"Kehui Liu , Hui Jiang , Rong Ji , Yuanyuan Ma , Rui Zhang , Binbin Song , Ying Han","doi":"10.1016/j.tiv.2025.106074","DOIUrl":"10.1016/j.tiv.2025.106074","url":null,"abstract":"<div><div><em>Penthorum chinense</em> Pursh (<em>P. chinense</em>), known for its anti-inflammatory and antioxidant properties, is valued for its low toxicity in animal and human models. However, concerns have arisen regarding the developmental effects of its bioactive components. This study investigates the acute toxicity of <em>P. chinense</em> extract and gallic acid on zebrafish embryos. The calculated LC<sub>50</sub> values were 237.0 mg/L for <em>P. chinense</em> extract and 328.4 mg/L for gallic acid, demonstrating a dose-response relationship with increasing mortality rates. Developmental assessments revealed significant morphological abnormalities, including heart defects, swim bladder and tail malformations, particularly at higher concentrations. Body length and eye diameter showed a hormetic dose-response to <em>P. chinense</em> extract, with increased growth at lower concentrations but a decrease at higher doses. Cardiac evaluations revealed altered heart rates, initially increasing and then decreasing at elevated concentrations. qRT-PCR analyses confirmed modulation of several heart-related genes, highlighting the differential impacts on cardiac development. These findings underscore the need to carefully assess the potential risks of <em>P. chinense</em> extract and gallic acid exposure in aquatic organisms.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"107 ","pages":"Article 106074"},"PeriodicalIF":2.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864611","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

Species differences in microsomal metabolism of hydroxychloroquine 羟氯喹微粒体代谢的物种差异

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-04-14 DOI: 10.1016/j.tiv.2025.106063

Guilin Wei , Chaohua Yan , Liwei Zou , Yong Liu , Ling Yang

{"title":"Species differences in microsomal metabolism of hydroxychloroquine","authors":"Guilin Wei , Chaohua Yan , Liwei Zou , Yong Liu , Ling Yang","doi":"10.1016/j.tiv.2025.106063","DOIUrl":"10.1016/j.tiv.2025.106063","url":null,"abstract":"<div><div>Hydroxychloroquine (HCQ), a medication renowned for its anti-malarial and anti-autoimmune properties, is susceptible to drug-drug interactions (DDIs), particularly those involving cytochrome P450 enzymes (CYPs). The pharmacokinetic and metabolic profiles of HCQ across species are not well-characterized. In this study, we conducted a comparative analysis of HCQ metabolism and pharmacokinetics in human liver microsomes and those from various preclinical animal models. Metabolite profiling indicated that the mono-oxidized metabolite M5 was predominantly produced in microsomes from mouse (MLM), rats (RLM), dogs (DLM), and pigs (PLM). Conversely, two other oxidative metabolites, M4 and M6, were uniquely generated in PLM. Utilizing selective inhibitors of human CYP isoforms, we identified key enzymes in HLM that differ from those in other species. Furthermore, the metabolic pathways in HLM were distinct from those observed in other species. In HLM, two metabolic pathways have been identified, each comprising a two-step reaction. CYP2D6, CYP2C8, CYP3A4, and CYP1A1 are the key enzymes involved in HCQ metabolism, with HCQ demonstrating significant substrate inhibition of CYP2D6, CYP2C8, and CYP1A1. Our work shed a new light on selection of suitable experimental animal models for accurate evaluation of HCQ's <em>in vivo</em> processes and its potential in multi-drug regimens.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"107 ","pages":"Article 106063"},"PeriodicalIF":2.6,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844908","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

Antibiotics reduce intestinal bile acid reuptake in an in vitro model system 抗生素在体外模型系统中减少肠道胆汁酸再摄取

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-04-09 DOI: 10.1016/j.tiv.2025.106071

Nina Zhang, Véronique M.P. de Bruijn, Weijia Zheng, Wouter Bakker, Bennard van Ravenzwaay, Ivonne M.C.M. Rietjens

{"title":"Antibiotics reduce intestinal bile acid reuptake in an in vitro model system","authors":"Nina Zhang, Véronique M.P. de Bruijn, Weijia Zheng, Wouter Bakker, Bennard van Ravenzwaay, Ivonne M.C.M. Rietjens","doi":"10.1016/j.tiv.2025.106071","DOIUrl":"10.1016/j.tiv.2025.106071","url":null,"abstract":"<div><div>Enterohepatic circulation of bile acids is a highly efficient process that is important for bile acid homeostasis. The aim of the present study was to characterize the impact of a series of antibiotics (lincomycin, streptomycin, vancomycin and tobramycin) on the intestinal reuptake of conjugated bile acids (TCA, TCDCA, GCA and GCDCA) using a Caco-2 <em>in vitro</em> transwell model system. The results obtained demonstrate that both pre-exposure and co-exposure of the cells to an antibiotic and the bile acids, affected bile acid transport, to an extent that depended on the antibiotic, its concentration and the type of conjugated bile acid tested. Tobramycin, at concentrations in line with dose levels at which this antibiotic induced effects on bile acid homeostasis <em>in vivo</em>, appeared able to inhibit bile acid transport after pre-exposure of the cells, likely resulting from an effect on the expression of bile acid transporters <em>via</em> its effects on protein synthesis at ribosome level. Upon co-exposure of the Caco-2 cells to an antibiotic and the bile acids, all four antibiotics appeared to significantly reduce the transport of especially the conjugated bile acids TCDCA and GCDCA with a potency that decreased in the order vancomycin > tobramycin = streptomycin > lincomycin. The effects observed illustrate the possibility of using a new approach methodology (NAM) to study effects on intestinal bile acid reuptake.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"107 ","pages":"Article 106071"},"PeriodicalIF":2.6,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844907","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

Corrigendum to “Tetrazolium–based colorimetric assays underestimat the direct antitumor effects of bevacizumab” [Toxicology in vitro 91 (2023) 105631] “基于四氮唑的比色法测定低估了贝伐单抗的直接抗肿瘤作用”的勘误表[体外毒理学91(2023)105631]。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-04-09 DOI: 10.1016/j.tiv.2025.106061

Pei Wei , Min Wang , Mao Lin , Zhiyong Wang

引用次数: 0