Toxicology in Vitro最新文献

Comparison of the behavior of human lung epithelial cell lines cultured at the air-liquid interface and assessment of their responses after benzo(a)pyrene exposure 在气液界面培养的人肺上皮细胞系的行为比较及其暴露于苯并(a)芘后的反应评估

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-07-23 DOI: 10.1016/j.tiv.2025.106122

Suen Boulé, Louise Verhaeghe, Dominique Courcot, Yann Landkocz

{"title":"Comparison of the behavior of human lung epithelial cell lines cultured at the air-liquid interface and assessment of their responses after benzo(a)pyrene exposure","authors":"Suen Boulé, Louise Verhaeghe, Dominique Courcot, Yann Landkocz","doi":"10.1016/j.tiv.2025.106122","DOIUrl":"10.1016/j.tiv.2025.106122","url":null,"abstract":"<div><div>The biological effects of air pollution are still not well known, due to its complex mixture of particulate and gaseous compounds. <em>In vitro</em> cell culture models exposed at the air-liquid interface (ALI) represent a potential alternative to <em>in vivo</em> experiments to assess the effects of outdoor air pollution. This study compares two bronchial cell lines, Calu-3 and BEAS-2B, and two alveolar cell lines, hAELVi and A549, regarding their capacity to form a tight epithelial cell barrier for a 2-week culture period and metabolize xenobiotics actively. Culture at the air-liquid interface permits the Calu-3 and hAELVi cells to form and maintain a tight epithelial cell barrier with lower permeability to lucifer yellow, greater trans-epithelial electrical resistance, and the presence of <em>Zonula Occludens 1</em> (ZO-1) protein at the membrane, than the BEAS-2B and A549 cells. Exposure to benzo(<em>a</em>)pyrene (B<em>a</em>P) induces the up-regulation of CYP1A1 and CYP1B1 genes, proteins, and functional activity at the air-liquid interface in all cell lines. So, these results demonstrate that the Calu-3 and the hAELVi cells are the more relevant models to assess the effects of ambient air pollution at the air-liquid interface, forming a tight epithelial cell barrier and being metabolically active.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"109 ","pages":"Article 106122"},"PeriodicalIF":2.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144704469","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

Polystyrene nanoplastic co-exposed to BPA and BPS induces cytotoxicity, genotoxicity, and alters ROS production in HepG2 cells 聚苯乙烯纳米塑料共同暴露于BPA和BPS诱导细胞毒性，遗传毒性，并改变HepG2细胞的ROS产生

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-07-23 DOI: 10.1016/j.tiv.2025.106121

Cecilia Cristina de Souza Rocha , Caroline Andolfato Sanchez , Marília Cristina Oliveira Souza , Estéfani Maria Treviso , Gabriel Henrique Savietto , Paula Pícoli Devóz , Lucas Victor Pereira de Freitas , Lusânia Maria Greggi Antunes , Jonas Augusto Rizzato Paschoal , Fernando Barbosa Junior

{"title":"Polystyrene nanoplastic co-exposed to BPA and BPS induces cytotoxicity, genotoxicity, and alters ROS production in HepG2 cells","authors":"Cecilia Cristina de Souza Rocha , Caroline Andolfato Sanchez , Marília Cristina Oliveira Souza , Estéfani Maria Treviso , Gabriel Henrique Savietto , Paula Pícoli Devóz , Lucas Victor Pereira de Freitas , Lusânia Maria Greggi Antunes , Jonas Augusto Rizzato Paschoal , Fernando Barbosa Junior","doi":"10.1016/j.tiv.2025.106121","DOIUrl":"10.1016/j.tiv.2025.106121","url":null,"abstract":"<div><div>During plastic degradation, it is fragmented into micro and nanoplastic, which can adsorb contaminants from the environment, increasing the plastics´ toxicity. Bisphenol A is used in plastic production and can be an endocrine disruptor. Bisphenol S is an analog of bisphenol A and has been used as an alternative to “BPA-free” products. Therefore, this is the first research proposing to verify whether nanoplastics associated with bisphenol A or S can increase toxicity in HepG2 cells. Nanoplastics associated with bisphenols could alter the cell viability of HepG2 cells compared to the group treated with the nanoplastic alone and concerning the respective bisphenol. The co-exposure of nanoplastic to bisphenols A or S promoted cytotoxic and genotoxic damage in HepG2 cells, altering the reactive oxygen species production, increasing DNA strand breaks, and increasing apoptotic cells. Bisphenols A and S also showed cytotoxic and genotoxic effects in HepG2 cells. However, 8-OHdG was only detected in the group treated with the nanoplastic at the lowest concentration. This study highlights the cytotoxicity and genotoxicity of nanoplastics and bisphenols A and S, providing new insights into hepatocyte toxicity.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"109 ","pages":"Article 106121"},"PeriodicalIF":2.6,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144704468","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 neuroprotective role of chlorogenic acid and Fisetin in differentiated neuronal cell line-SHSY5Y against amyloid-β-induced neurotoxicity 绿原酸和非西汀对分化神经细胞系shsy5y抗淀粉样蛋白β诱导的神经毒性的保护作用。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-07-20 DOI: 10.1016/j.tiv.2025.106110

Apoorv Sharma , Puneet Kumar , Asimul Islam , Monika Bhardwaj , Vijay Kumar , Hridayesh Prakash

{"title":"The neuroprotective role of chlorogenic acid and Fisetin in differentiated neuronal cell line-SHSY5Y against amyloid-β-induced neurotoxicity","authors":"Apoorv Sharma , Puneet Kumar , Asimul Islam , Monika Bhardwaj , Vijay Kumar , Hridayesh Prakash","doi":"10.1016/j.tiv.2025.106110","DOIUrl":"10.1016/j.tiv.2025.106110","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a neurodegenerative disorder and characterized by amyloid-beta (Aβ) accumulation, synaptic dysfunction, oxidative stress, and lacks effective therapies. Fisetin and chlorogenic acid (CGA) are natural polyphenols have shown potential in mitigating several age-related diseases. Therefore this study investigates their neuroprotective effects against Aβ1–42-induced toxicity in differentiated SHSY5Y cells. Both Fisetin and CGA reversed the deleterious effects of Aβ1–42 by restoring redox balance, suppressing reactive oxygen species, and upregulating mRNA expression of critical antioxidant enzymes like <em>SOD1, GSR,</em> and <em>CAT</em>. These compounds also attenuated Aβ1–42-induced mitophagy via reduced <em>PINK1</em> expression and restored mitochondrial fusion by upregulating <em>MFN2</em>. Autophagy-related pathways were significantly modulated which was evidenced by increased <em>PRKAA1</em> (AMPK) and decreased <em>MTOR</em> mRNA levels, alongside elevated expression of <em>ATG101, ATG13, ULK1, SQSTM1</em> (p62) and reduced <em>ATG5</em> levels. Fisetin and CGA improved synaptic integrity by upregulating <em>DLG4</em> (PSD95) and <em>SYP</em> (synaptophysin) and reducing <em>ACHE</em> (acetylcholinesterase) expression. These findings highlight their potential in ameliorating Aβ1–42-induced neuronal toxicity through autophagy activation, synaptic preservation, and mitochondrial function enhancement. Furthermore, our docking studies also revealed good Fisetin and CGA binding affinity within AMPK and mTOR's binding pocket (FKBP12-FRB). Although the neuroprotective effects of CGA and Fisetin are underscored by transcriptional and docking studies, further translational and biophysical validation is required to demonstrate their therapeutic efficacy against AD-related neurodegeneration.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"109 ","pages":"Article 106110"},"PeriodicalIF":2.6,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692471","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

Beyond traditional toxicology: The transformative power of PBTK modeling 超越传统毒理学：PBTK建模的变革力量

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-07-18 DOI: 10.1016/j.tiv.2025.106111

Anagha Damre, Aniruddha Banerjee

{"title":"Beyond traditional toxicology: The transformative power of PBTK modeling","authors":"Anagha Damre, Aniruddha Banerjee","doi":"10.1016/j.tiv.2025.106111","DOIUrl":"10.1016/j.tiv.2025.106111","url":null,"abstract":"<div><div>Physiologically Based Toxicokinetic (PBTK) modeling has emerged as a crucial tool in toxicokinetics, enabling the quantitative assessment of chemical absorption, distribution, metabolism, and excretion (ADME) across various biological systems. Unlike traditional toxicokinetic approaches, PBTK models integrate physiological and biochemical parameters to allow for precise interspecies and dose extrapolations. This capability enhances their applicability in regulatory risk assessment for pharmaceuticals, industrial chemicals, food additives, cosmetics, and pesticides. High Throughput Toxicokinetics (HTTK) and in vitro-to-in vivo extrapolations (IVIVE) further improve the predictive power of PBTK models by utilizing large-scale experimental datasets and computational approaches. Additionally, these models facilitate route-to-route extrapolations, predicting systemic exposure across different administration routes such as oral, inhalation, and dermal pathways. PBTK modeling also enables the estimation of specific target tissue concentrations, cross-species extrapolations, and extrapolations to special populations, thereby improving human biological modeling. Furthermore, the integration of PBTK models in ecological risk assessment supports the evaluation of environmental chemical exposure effects on diverse species. As regulatory agencies increasingly adopt PBTK models for toxicity evaluations, their role in advancing data-driven risk assessment and reducing reliance on animal testing continues to grow. This review explores the application of PBTK modeling in toxicokinetics and its alignment with regulatory guidelines for risk assessment and interspecies extrapolation.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"109 ","pages":"Article 106111"},"PeriodicalIF":2.6,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144672141","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

Inter-laboratory validation study of an in vitro glucocorticoid receptor transactivation assay for testing potential endocrine disrupting chemicals 用于检测潜在内分泌干扰物的体外糖皮质激素受体反激活试验的实验室间验证研究。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-07-17 DOI: 10.1016/j.tiv.2025.106109

Andrea Rivero-Arze , Marina Grimaldi , Géraldine Maillet , Cindie Gesbert , Erwan Michelin , Clémentine Garoche , Emmanuelle Maillot-Maréchal , Olivier Palluel , François Sermier , Sebastian Hoffmann , Jérôme Couteau , Philippe Hubert , Elise Grignard , Selim Aït-Aïssa , Patrick Balaguer , Torben Österlund

{"title":"Inter-laboratory validation study of an in vitro glucocorticoid receptor transactivation assay for testing potential endocrine disrupting chemicals","authors":"Andrea Rivero-Arze , Marina Grimaldi , Géraldine Maillet , Cindie Gesbert , Erwan Michelin , Clémentine Garoche , Emmanuelle Maillot-Maréchal , Olivier Palluel , François Sermier , Sebastian Hoffmann , Jérôme Couteau , Philippe Hubert , Elise Grignard , Selim Aït-Aïssa , Patrick Balaguer , Torben Österlund","doi":"10.1016/j.tiv.2025.106109","DOIUrl":"10.1016/j.tiv.2025.106109","url":null,"abstract":"<div><div>The glucocorticoid receptor (GR) belongs to the family of steroid receptors (SRs). These receptors regulate a vast selection of cell-, tissue-, and organism biology, and are also targets of endocrine disrupting chemicals warranting design and validation of <em>in vitro</em> assays. Here we report a “blinded” ring trial of an <em>in vitro</em> cell-based GR transactivation assay with four involved laboratories. The laboratories set up the assay and tested 34 selected chemicals with remarkably good concordance. There was agreement between all laboratories for the classification of activity in 97 % of the cases, and three or more laboratories were always in agreement. The within laboratory concordance was very high (99.6 %) with only one of all 272 triplicates deviating. The assay was, thus, deemed easily transferable and reproducible within and between laboratories, since they would arrive at the same qualitative results. Furthermore, for the chemicals with solid data regarding GR activation or inhibition, the laboratories arrived at the expected conclusion in all cases. Overall, the transfer and validation were successful, and the method is under evaluation to become an OECD test guideline. The method is expected to become valuable in tiered approaches for assessing chemicals or environmental samples together with other similar methods.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"109 ","pages":"Article 106109"},"PeriodicalIF":2.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669008","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

Lupeol-loaded PLGA particles conserve anti-topoisomerase activity and decrease the cytotoxicity of lupeol 负载lupeol的PLGA颗粒保持抗拓扑异构酶活性，降低lupeol的细胞毒性。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-07-15 DOI: 10.1016/j.tiv.2025.106107

Francisco Fabián Razura-Carmona , Mayra Herrera-Martínez , Jorge Alberto Sánchez-Burgos , Alejandro Pérez-Larios , Karina Janice Guadalupe Díaz-Reséndiz , Manuel Iván Girón-Pérez , Marco Vinicio Ramírez-Mares

{"title":"Lupeol-loaded PLGA particles conserve anti-topoisomerase activity and decrease the cytotoxicity of lupeol","authors":"Francisco Fabián Razura-Carmona , Mayra Herrera-Martínez , Jorge Alberto Sánchez-Burgos , Alejandro Pérez-Larios , Karina Janice Guadalupe Díaz-Reséndiz , Manuel Iván Girón-Pérez , Marco Vinicio Ramírez-Mares","doi":"10.1016/j.tiv.2025.106107","DOIUrl":"10.1016/j.tiv.2025.106107","url":null,"abstract":"<div><div>Lupeol (LP), a bioactive triterpene, has been extensively studied for its chemoprotective, anti-inflammatory, and anti-arthritic properties. To enhance its bioavailability, lupeol-loaded polylactic-<em>co</em>-glycolic acid (PLGA) nanoparticles, designated T<sub>LP</sub>14, were developed using the emulsification-evaporation method. These nanoparticles exhibited an average size of 339.8 nm, a polydispersity index (PdI) of 0.240, and an encapsulation efficiency of 38 %. In topoisomerase II inhibition assays, T<sub>LP</sub>14 retained activity comparable to that of lupeol free, indicating that encapsulation does not impair its biological function. <em>In vitro</em> cytotoxicity assays on BEAS-2 and HEPG2 cell lines demonstrated that concentrations above 1250 μg/mL of T<sub>LP</sub>14 induced minimal cytotoxic effects, suggesting low toxicity in non-tumor cells. Furthermore, <em>ex vivo</em> studies on peripheral blood mononuclear cells showed that a 1000 μg/mL concentration of free lupeol induced 28.01 % apoptosis, while the encapsulated formulation significantly reduced this adverse effect. These findings support the potential of T<sub>LP</sub>14 nanoparticles as an effective controlled-release system for lupeol, enhancing its safety profile while preserving its therapeutic activity.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"109 ","pages":"Article 106107"},"PeriodicalIF":2.6,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661008","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

Impact of gadolinium oxide based nanoparticles on genotoxic, cytotoxic and oxidative stress in human lymphocytes 氧化钆纳米颗粒对人淋巴细胞基因毒性、细胞毒性和氧化应激的影响。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-07-13 DOI: 10.1016/j.tiv.2025.106106

Isela Álvarez-González , Lizbeth Espinosa-García , Felipe de Jesús Carrillo-Romo , Antonieta García-Murillo , José A. Morales-González , Eduardo O. Madrigal-Santillán , Eduardo Madrigal-Bujaidar

{"title":"Impact of gadolinium oxide based nanoparticles on genotoxic, cytotoxic and oxidative stress in human lymphocytes","authors":"Isela Álvarez-González , Lizbeth Espinosa-García , Felipe de Jesús Carrillo-Romo , Antonieta García-Murillo , José A. Morales-González , Eduardo O. Madrigal-Santillán , Eduardo Madrigal-Bujaidar","doi":"10.1016/j.tiv.2025.106106","DOIUrl":"10.1016/j.tiv.2025.106106","url":null,"abstract":"<div><div>Gadolinium-based nanoparticles are presently applied in biomedicine and industry, and their potential is increasing. In this report we synthetized three nanoparticles by the sol-gel, supercritical drying method: Gd<sub>2</sub>O<sub>3</sub>, Gd<sub>2</sub>O<sub>3</sub> doped with Eu<sup>+3</sup>, and Gd<sub>2</sub>O<sub>3</sub> doped with Eu<sup>+3</sup>and functionalized with thenoyltrifluoroacetone (TTA). The nanoparticles were characterized for luminescence, morphology, size, and Z potential. The results showed that the highest luminescence was reached with the TTA functionalized nanoparticle, all of them had a porous net structure that decreased to 21 nm in the last nanoparticle, and the Z potential was found from −2 to −12 mV. To determine their geno/cytotoxic potential we performed the cytochalasine-block micronucleus cytome, and the MTT assays in human lymphocytes. With these assays, we demonstrated that the two main genotoxic effects were the nuclear buds and nucleoplasmic bridges, and that nanoparticles decreased the cellular proliferation, mainly because of the induction of apoptosis (about 70 %) in contrast with the 30 % of necrosis. Finally, a significant lipid and protein oxidation increase was determined in the nanoparticles. Our results suggest that the observed geno/cytotoxic damage may be related with the presence of oxidative stress.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"109 ","pages":"Article 106106"},"PeriodicalIF":2.6,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144644152","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

Testing chemicals for CYP19 inhibition: Comparison of a modified H295R steroidogenesis assay to a commercial fluorometric enzyme inhibition kit 检测CYP19抑制的化学物质：改良的H295R甾体生成试验与商业荧光酶抑制试剂盒的比较。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-07-13 DOI: 10.1016/j.tiv.2025.106108

Caroline Despicht, Kieu-Mi Tran, Terje Svingen, Anna Kjerstine Rosenmai

{"title":"Testing chemicals for CYP19 inhibition: Comparison of a modified H295R steroidogenesis assay to a commercial fluorometric enzyme inhibition kit","authors":"Caroline Despicht, Kieu-Mi Tran, Terje Svingen, Anna Kjerstine Rosenmai","doi":"10.1016/j.tiv.2025.106108","DOIUrl":"10.1016/j.tiv.2025.106108","url":null,"abstract":"<div><div>Aromatase (CYP19A1) is a key enzyme that converts androgens to estrogens. Given its central role in estrogen biosynthesis, aromatase is a target of endocrine disruption. Aromatase disruption can be measured in vitro with cell-free enzyme assays or using cells expressing CYP19A1. Results may vary between models, as cell-based models can have adaptive responses not present in enzyme assays. Here, we have compared 21 chemicals for their ability to affect aromatase by direct and indirect disruption using an aromatase commercial kit and a modified H295R steroidogenesis assay. New data was generated for eighteen test compounds in either one or both of the models. Chemicals eliciting a response could be divided into five categories: 1) substances that decreased the response in both models, 2) substances that directly inhibited aromatase, but increased 17β-estradiol (E2) levels in H295R assay, 3) substances that directly inhibited aromatase, but did not affect E2 levels in H295R assay, 4) substances that did not inhibit aromatase activity, but increased E2 levels in the H295R model, and 5) substances that did not alter responses in either of the assays. These results illustrate that both assays are useful for assessing the potential of chemicals to affect E2 levels either through direct aromatase inhibition or other indirect mechanisms.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"109 ","pages":"Article 106108"},"PeriodicalIF":2.6,"publicationDate":"2025-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144644153","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

E171-induced toxicity in human iPSC-derived colon organoids: Effects on cell viability, ROS generation, DNA damage, and gene expression changes e171诱导的人类ipsc衍生的结肠类器官毒性：对细胞活力、ROS生成、DNA损伤和基因表达变化的影响

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-07-10 DOI: 10.1016/j.tiv.2025.106105

Nicolaj S. Bischoff , Anna K. Undas , Marcel van Herwijnen , Marcha Verheijen , Jacco J. Briedé , Simone G. van Breda , Dick T.H.M. Sijm , Theo M. de Kok

{"title":"E171-induced toxicity in human iPSC-derived colon organoids: Effects on cell viability, ROS generation, DNA damage, and gene expression changes","authors":"Nicolaj S. Bischoff , Anna K. Undas , Marcel van Herwijnen , Marcha Verheijen , Jacco J. Briedé , Simone G. van Breda , Dick T.H.M. Sijm , Theo M. de Kok","doi":"10.1016/j.tiv.2025.106105","DOIUrl":"10.1016/j.tiv.2025.106105","url":null,"abstract":"<div><div>Food-grade titanium dioxide (E171) is a widely used food additive with debated safety, particularly regarding its genotoxic effects. This study assessed the dose-dependent toxicity of E171 in human induced pluripotent stem cell (iPSC)-derived colon organoids. Organoids were exposed to E171 (0.1–1000 μg/mL) for 24 h, and effects on cell viability, reactive oxygen species (ROS) generation, DNA damage, and gene expression were evaluated.</div><div>Results showed no impact on cell viability but a dose-dependent increase in ROS formation, peaking at 1000 μg/mL. Electrospin Resonance Spectroscopy (ESR) showed a dose-dependent increase in ROS, with increased E171 concentrations. The alkaline comet assay revealed significant DNA damage from 100 μg/mL, with oxidative DNA damage detected at 10 μg/mL using formamidopyrimidine DNA glycosylase (FPG). RNA sequencing identified differentially expressed genes (DEGs) at 100 and 250 μg/mL, linked to translational activity, signal transduction, and DNA damage repair. Gene set enrichment analysis (GSEA) indicated activation of ribosome, chemical carcinogenesis–ROS, and metabolic pathways (carbon metabolism, glycolysis), while key regulatory pathways (Wnt, MAPK, PI3K-Akt) were suppressed.</div><div>These findings suggest that E171 induces oxidative stress and DNA damage, modulating transcriptomic pathways associated with metabolism, proliferation, and cancer. Further research is necessary to determine its long-term effects on human gastrointestinal health.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"108 ","pages":"Article 106105"},"PeriodicalIF":2.6,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144614228","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 protective mechanisms of glycyrrhizic acid for deoxynivalenol-induced toxicity in rabbit corneal stroma 甘草酸对脱氧雪腐镰刀醇致兔角膜基质毒性的保护机制。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-07-04 DOI: 10.1016/j.tiv.2025.106104

Chunlan Liang , Xuewei Xiong , Qi Shi , Qingqing Li , Guocheng Yu , Jingxiang Zhong , Lian Liu

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