Toxicology in Vitro最新文献_第2页

Diesel exhaust nanoparticles: Cellular adaptation in lung epithelial and fibroblast cells – An in vitro study 柴油废气纳米颗粒：肺上皮细胞和成纤维细胞的细胞适应性-体外研究。

IF 2.7 3区医学

Toxicology in Vitro Pub Date : 2026-04-01 Epub Date: 2026-01-03 DOI: 10.1016/j.tiv.2026.106193

Gabriel Martínez-Razo , Ruth Angélica Lezama , Armando Vega-López , María Lilia Domínguez-López

{"title":"Diesel exhaust nanoparticles: Cellular adaptation in lung epithelial and fibroblast cells – An in vitro study","authors":"Gabriel Martínez-Razo , Ruth Angélica Lezama , Armando Vega-López , María Lilia Domínguez-López","doi":"10.1016/j.tiv.2026.106193","DOIUrl":"10.1016/j.tiv.2026.106193","url":null,"abstract":"<div><div>Diesel exhaust particles (DEnP) represent a major urban air pollutant with known adverse effects on human health, yet detailed cellular interactions at the nanoscale are poorly understood. This study aims to elucidate the cellular responses and adaptation mechanisms of human lung epithelial and fibroblast-like cell lines exposed to Mexican diesel exhaust nanoparticles. Exhaust samples from cold and warm engine emissions were analyzed for polyaromatic hydrocarbons, organic matter, and elemental composition using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Additionally, the DEnP nanostructure was scrutinized using 3D topographical image analysis. In vitro assays assessed cell proliferation, adhesion molecule expression (ICAM-1, VCAM-1), and proteins related to endocytosis (clathrin and dynamin) in response to DEnP exposure. SEM and TEM analyses revealed distinct nanoparticle forms and compositions, with significant increases in cell proliferation, endocytosis, and adhesion molecule expression observed, suggesting robust cellular adaptation mechanisms to counteract DEnP-induced stress. The study confirms significant cellular adaptations in response to DEnP, underscoring the need for preventive strategies to mitigate the impacts of exposure. These findings provide a foundation for further investigation into long-term cellular adaptations and their implications for pulmonary health.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"112 ","pages":"Article 106193"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906726","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

Activation of Toll-like receptor 2 reveals microbial contamination beyond endotoxins on micro- and nanoplastics toll样受体2的激活揭示了微和纳米塑料上的内毒素以外的微生物污染。

IF 2.7 3区医学

Toxicology in Vitro Pub Date : 2026-04-01 Epub Date: 2025-12-13 DOI: 10.1016/j.tiv.2025.106190

Øyvind P. Haugen , Itziar Polanco-Garriz , Victor Alcolea-Rodriguez , Raquel Portela , Rita Bæra , Hamed Sadeghiankaffash , Jana Hildebrandt , Dmitri Ciornii , Korinna Altmann , Francesco Barbero , Ivana Fenoglio , Julián J. Reinosa , José F. Fernández , Alberto Katsumiti , Laura M.A. Camassa , Håkan Wallin , Shan Zienolddiny-Narui , Anani K. Afanou

{"title":"Activation of Toll-like receptor 2 reveals microbial contamination beyond endotoxins on micro- and nanoplastics","authors":"Øyvind P. Haugen , Itziar Polanco-Garriz , Victor Alcolea-Rodriguez , Raquel Portela , Rita Bæra , Hamed Sadeghiankaffash , Jana Hildebrandt , Dmitri Ciornii , Korinna Altmann , Francesco Barbero , Ivana Fenoglio , Julián J. Reinosa , José F. Fernández , Alberto Katsumiti , Laura M.A. Camassa , Håkan Wallin , Shan Zienolddiny-Narui , Anani K. Afanou","doi":"10.1016/j.tiv.2025.106190","DOIUrl":"10.1016/j.tiv.2025.106190","url":null,"abstract":"<div><div>Current literature on health hazards associated with micro- and nanoplastics (MNPs) is largely influenced by studies that insufficiently account for potential microbial contamination of their test materials. This may lead to misinterpretation of outcomes, as the test materials may be incorrectly considered pristine MNPs. The present study screened eight MNP test materials for microbial contaminants using Toll-like receptor (TLR) reporter cells for TLR2 and TLR4 and the commonly used Limulus amebocyte lysate (LAL) assay. Our results show that MNPs testing negative for endotoxins, based on the absence of TLR4 activation and negative LAL results, may still contain microbial ligands that selectively activate TLR2. Moreover, five of the eight MNP test materials contained microbial ligands capable of activating TLR2 and/or TLR4. Compared to the LAL assay, TLR4-based screening effectively detected endotoxin contamination. Overall, we found that the TLR reporter cell assay provides broader coverage than the LAL assay in detecting microbial ligands, which appear to be highly prevalent in MNP test materials.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"112 ","pages":"Article 106190"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145764308","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

Chemical characterisation and cytotoxic analysis of an electronic cigarette and heated tobacco product compared to a conventional cigarette in human lung cell lines 电子烟和加热烟草制品与传统香烟在人肺细胞系中的化学特性和细胞毒性分析。

IF 2.7 3区医学

Toxicology in Vitro Pub Date : 2026-04-01 Epub Date: 2026-01-17 DOI: 10.1016/j.tiv.2026.106199

Gregory Rankin , Håkan Wingfors , Linda Öberg , Anders Blomberg , Linnea Hedman , Jenny A. Bosson , Magnus Lundbäck

{"title":"Chemical characterisation and cytotoxic analysis of an electronic cigarette and heated tobacco product compared to a conventional cigarette in human lung cell lines","authors":"Gregory Rankin , Håkan Wingfors , Linda Öberg , Anders Blomberg , Linnea Hedman , Jenny A. Bosson , Magnus Lundbäck","doi":"10.1016/j.tiv.2026.106199","DOIUrl":"10.1016/j.tiv.2026.106199","url":null,"abstract":"<div><div>The use of electronic nicotine delivery systems, such as e-cigarettes and heated tobacco products (HTPs), is increasing, but knowledge of their short and long-term toxicological effects remains limited. Here, aerosols generated from an e-cigarette using a flavour-free e-liquid base, both with and without nicotine, an HTP, and a conventional cigarette were characterised for the production of polycyclic aromatic hydrocarbons (PAHs), carbonyls and volatile organic compounds (VOCs). Furthermore, extracts from vapour and smoke were generated, and their acute toxicity was assessed in human lung epithelial cells and fibroblasts. Cigarette smoke contained significantly more toxic compounds and induced the highest degree of toxicity in all the tested cell lines, followed by the HTP, and then the nicotine containing e-cigarette. Notably, the nicotine containing e-cigarette produced similar levels of formaldehyde as the HTP and cigarette smoke, and caused a greater decrease in cell viability in primary lung fibroblasts compared to the nicotine-free e-cigarette. Although the HTP aerosol contained lower levels of toxicants than cigarette smoke, some VOCs specific to HTPs were detected. More independent research is needed to identify toxicant-specific production in emerging nicotine delivery systems and their potential health impacts to better inform policy makers, health care providers and the general public.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"112 ","pages":"Article 106199"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146004717","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 and Ci-hAELVi cell lines coculture as a new human alveolar epithelium model for air-liquid interface exposure A549和CI-hAELVi细胞系共培养作为新的人肺泡上皮气液界面暴露模型。

IF 2.7 3区医学

Toxicology in Vitro Pub Date : 2026-04-01 Epub Date: 2026-01-27 DOI: 10.1016/j.tiv.2026.106200

Aurelia Alunni , Ophélie Simonin , Guillaume Barbier , Maxime Floreani , Alexandre Albinet , Guillaume Garçon , Bénédicte Trouiller

{"title":"A549 and Ci-hAELVi cell lines coculture as a new human alveolar epithelium model for air-liquid interface exposure","authors":"Aurelia Alunni , Ophélie Simonin , Guillaume Barbier , Maxime Floreani , Alexandre Albinet , Guillaume Garçon , Bénédicte Trouiller","doi":"10.1016/j.tiv.2026.106200","DOIUrl":"10.1016/j.tiv.2026.106200","url":null,"abstract":"<div><div>Air pollution represents a growing threat to human health, particularly affecting the respiratory system through the inhalation of gaseous pollutants and fine particles that reach the alveolar region composed mainly of alveolar epithelial type I (AT1) and type II (AT2) cells at the air-liquid interface (ALI). To reduce reliance on animal models, physiologically relevant and experimentally accessible <em>in vitro</em> models are increasingly needed for inhalation toxicology. In this study, we developed and characterized a simple and robust human alveolar coculture model at ALI using commercially available cell lines, A549 (AT2 phenotype-like) and Ci-hAELVi (AT1 phenotype-like). Two ALI acclimatization periods (24 h and six days) were evaluated under incubator control and clean air exposure conditions. The coculture exhibited stable metabolic activity, controlled proliferation, and reduced variability compared to monoculture. The model expressed complementary AT1- (Podoplanin, Caveolin-1, Aquaporin-5, HTI56) and AT2 pneumocyte-associated markers (surfactant proteins and HTII280) at the gene and protein levels, resulting in a mix of both the alveolar epithelial phenotypes. Importantly, the coculture model maintained epithelial integrity and functional stability during prolonged ALI exposure for up to 72 h, exceeding the typical exposure window of monoculture system. In addition, responsiveness of coculture with ZnO aerosol and lipopolysaccharides exposure, was tested demonstrating its functional relevance. Overall, this relevant coculture model provides a valuable <em>in vitro</em> tool for preliminary toxicological screening.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"112 ","pages":"Article 106200"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146088045","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

Conditioned medium from 1-nitropyrene induced THP-1 foam cells promotes pro-tumorigenesis in lung epithelial cells 1-硝基芘诱导THP-1泡沫细胞的条件培养基促进肺上皮细胞的促肿瘤发生。

IF 2.7 3区医学

Toxicology in Vitro Pub Date : 2026-04-01 Epub Date: 2026-01-22 DOI: 10.1016/j.tiv.2026.106197

Ankita Bagde , Atul Katarkar , K. Krishnamurthi

{"title":"Conditioned medium from 1-nitropyrene induced THP-1 foam cells promotes pro-tumorigenesis in lung epithelial cells","authors":"Ankita Bagde , Atul Katarkar , K. Krishnamurthi","doi":"10.1016/j.tiv.2026.106197","DOIUrl":"10.1016/j.tiv.2026.106197","url":null,"abstract":"<div><div>Diesel exhaust (DE) is a major environmental pollutant containing fine particulate matter and polycyclic aromatic hydrocarbons (PAHs). Among its constituents, 1-nitropyrene (1NP) is a recognized surrogate marker of DE. Although 1NP is known to induce oxidative stress and DNA damage in multiple cell types, its role in alveolar macrophage dysfunction and lung carcinogenesis remains poorly defined. In this study we observed that 1NP drives foam cell formation in THP-1–derived macrophages through activation of the aryl hydrocarbon receptor (AhR). Exposure to 1NP induced AhR nuclear translocation and lipid accumulation, as demonstrated by AhR immunofluorescence and Oil Red O/Nile Red staining, SEM analysis, while pharmacological inhibition of AhR markedly attenuated these effects. 1NP-induced foam cells displayed elevated IL-6 and TNF-α mRNA expression which correlated with increased secreted levels in the conditioned media and enhanced migratory behavior, both of which were suppressed by AhR inhibition. Importantly, conditioned media from 1NP-driven foam cells enhanced A549 pro-tumorigenic phenotypes, promoting colony formation, spheroid growth, and migration. These pro-tumorigenic effects were abolished when AhR was inhibited during foam cell induction, revealing AhR-dependent paracrine mechanism. Our findings identify a previously unrecognized role for 1NP-induced foam cells in establishing a tumor-supportive lung microenvironment and position AhR as a central molecular link between environmental toxicant exposure, immune cell remodeling, and cancer progression.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"112 ","pages":"Article 106197"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044352","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

Vitamin E acetate and its aerosol activate aryl hydrocarbon receptor signaling and exacerbate inflammation in human U937-derived macrophages 维生素E醋酸酯及其气溶胶激活芳烃受体信号并加剧人u937源性巨噬细胞的炎症。

IF 2.7 3区医学

Toxicology in Vitro Pub Date : 2026-04-01 Epub Date: 2026-01-08 DOI: 10.1016/j.tiv.2026.106196

Xiaohan Li , Andrea Rossi , Thomas Haarmann-Stemmann , Elliot R. Spindel , Jack C. Connolly , Allison K. Ehrlich , Kent E. Pinkerton , Christoph F.A. Vogel

{"title":"Vitamin E acetate and its aerosol activate aryl hydrocarbon receptor signaling and exacerbate inflammation in human U937-derived macrophages","authors":"Xiaohan Li , Andrea Rossi , Thomas Haarmann-Stemmann , Elliot R. Spindel , Jack C. Connolly , Allison K. Ehrlich , Kent E. Pinkerton , Christoph F.A. Vogel","doi":"10.1016/j.tiv.2026.106196","DOIUrl":"10.1016/j.tiv.2026.106196","url":null,"abstract":"<div><div>In 2019, a number of patients were hospitalized after the use of electronic cigarettes and displayed acute lung injuries. Such injury was categorized as e-cigarette or vaping associated lung injury (EVALI). Among these patients, Vitamin E acetate (VEA) was detected in most used electronic cigarette cartridges as well as the patients' bronchoalveolar lavage fluid, suggesting VEA to be a culprit of causing lung injury. Although further experiments verified the potential of VEA aerosol to cause cytotoxicity and lung injury, mechanisms of VEA aerosol toxicity are not well understood. In this study, we tested the toxicity of VEA, and its aerosol using a human macrophage model. VEA aerosols significantly induced oxidative stress as well as proinflammatory responses. In addition, the aerosol activated the aryl hydrocarbon receptor (AhR) signaling pathway, inducing CYP1A1 expression in human U937 monocyte-derived macrophages. Additionally, non-aerosolized VEA and VEA aerosol induce the expression of inflammatory markers such as interleukin (IL)-8 and cyclooxygenase (COX)-2 in an AhR-dependent manner as shown in CRISPR-cas9 AhR-knockout U937-derived human macrophages. These results suggest that VEA is an agonist for AhR and provide new potential mechanisms for lung injury induced by VEA aerosol inhalation via AhR activation in addition to the generation of oxidative stress.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"112 ","pages":"Article 106196"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949433","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

Optimisation of ultrafine particle exposure in an alveolar tri-culture model at the air-liquid interface 在空气-液体界面的肺泡三培养模型中超细颗粒暴露的优化。

IF 2.7 3区医学

Toxicology in Vitro Pub Date : 2026-04-01 Epub Date: 2025-12-05 DOI: 10.1016/j.tiv.2025.106189

Anna-Katharina Hensel , Henri Hakkarainen , Mo Yang , Jingwen Huang , Laura Mussalo , Claire Fayad , Katja Kanninen , Pasi Jalava

{"title":"Optimisation of ultrafine particle exposure in an alveolar tri-culture model at the air-liquid interface","authors":"Anna-Katharina Hensel , Henri Hakkarainen , Mo Yang , Jingwen Huang , Laura Mussalo , Claire Fayad , Katja Kanninen , Pasi Jalava","doi":"10.1016/j.tiv.2025.106189","DOIUrl":"10.1016/j.tiv.2025.106189","url":null,"abstract":"<div><div>Air-liquid interface (ALI) systems have emerged as a physiologically relevant in vitro platform for evaluating the toxicological impact and potential health effects of airborne pollutants. When utilizing collected ultrafine particles (UFPs), application volume and liquid type are critical parameters. Using a smaller volume of liquid for the cell exposure results in a heterogeneous distribution of UFPs across the cell monolayer, whereas application of a sufficient volume optimises even UFP distribution. A buffered solution for UFP administration minimises potential side effects and unravels dose-dependent effects in toxicological endpoints. However, standardised exposure methodologies limit reproducibility and comparability across studies. Therefore, we propose a refined manual exposure technique of suspended airborne pollutants in an adequate exposure volume that bridges the gap between conventional submerged cultures and ALI systems. Our model uses cell culture inserts with A549 epithelial cells, THP-1 macrophages, and EA.hy926 endothelial cells to mimic the in vivo alveolar barrier within the lungs. This approach offers a balance of experimental reproducibility whilst addressing the current challenges of standardisation and feasibility in exposure studies with manual UFP exposure. In conjunction with existing aerosol ALI continuous flow exposure systems, our studies are advancing translational in vitro evaluations, aligning with the 3R principle.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"112 ","pages":"Article 106189"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145702516","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

Metabolic stability and effects of microsomal enzymes on the activity of the sonic hedgehog pathway inhibitor piperonyl butoxide 代谢稳定性和微粒体酶对超音hedgehog途径抑制剂胡椒酰丁醇活性的影响。

IF 2.7 3区医学

Toxicology in Vitro Pub Date : 2026-03-01 Epub Date: 2025-10-07 DOI: 10.1016/j.tiv.2025.106156

Kenneth S. Rivera-González , Cameron O. Scarlett , Robert J. Lipinski

{"title":"Metabolic stability and effects of microsomal enzymes on the activity of the sonic hedgehog pathway inhibitor piperonyl butoxide","authors":"Kenneth S. Rivera-González , Cameron O. Scarlett , Robert J. Lipinski","doi":"10.1016/j.tiv.2025.106156","DOIUrl":"10.1016/j.tiv.2025.106156","url":null,"abstract":"<div><div>The pesticide synergist piperonyl butoxide (PBO) is a methylenedioxy compound used in many pesticide formulations. Previous studies identified PBO as an inhibitor of the Sonic hedgehog (Shh) signaling pathway and linked prenatal PBO exposure to adverse developmental outcomes. Mixed-function oxidases have been proposed to metabolize PBO, but the specific enzymes involved in its depletion have not been identified. Here we examined the metabolic stability of PBO in the presence of human liver microsomes and the involvement of the CYP-450 (CYPs) and FMO enzyme families on the <em>in vitro</em> depletion of PBO. We found that PBO is readily depleted by microsomal enzymes in the presence of NADPH. The CYP inhibitor SKF-525 A significantly decreased PBO depletion, while the FMO inhibitor methimazole did not. We then examined the depletion capacity of individual CYPs, focusing on isoforms with common human polymorphisms. CYP2C19, CYP2C9, and CYP3A4 exhibited the greatest PBO depletion capacity, while CYP1A2 and CYP2D6 demonstrated moderate capacity. Finally, the effect of microsomal activity on the antagonist activity of PBO against the Sonic hedgehog (Shh) pathway was assessed. Microsomal depletion reduced but did not eliminate the antagonistic activity of PBO on Shh pathway signaling activity. Collectively, these findings suggest a major role for mixed-function oxidases in PBO depletion and indicate the possible involvement of specific CYP isoforms.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"111 ","pages":"Article 106156"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145253779","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

Effect of extraction vehicles on medical device sensitization testing by LuSens assay 提取载体对LuSens法医疗器械敏化试验的影响。

IF 2.7 3区医学

Toxicology in Vitro Pub Date : 2026-03-01 Epub Date: 2025-10-14 DOI: 10.1016/j.tiv.2025.106167

L. Svobodova , E. Pacalova , K. Kejlova , A. Vlkova , M. Dvorakova , M. Rucki , D. Jirova , H. Bendova

{"title":"Effect of extraction vehicles on medical device sensitization testing by LuSens assay","authors":"L. Svobodova , E. Pacalova , K. Kejlova , A. Vlkova , M. Dvorakova , M. Rucki , D. Jirova , H. Bendova","doi":"10.1016/j.tiv.2025.106167","DOIUrl":"10.1016/j.tiv.2025.106167","url":null,"abstract":"<div><div>Skin sensitization risk of medical devices (MDs) has to be assessed before their marketing and clinical use. The obligatory methods (ISO 10993-10:2021) include exclusively <em>in vivo</em> tests, however, validated non-animal methods might be utilized after successful verification of their applicability in the specific field of MDs and their extracts. One of the candidate <em>in vitro</em> tests is the LuSens assay (OECD TG 442D), which covers the Key Event 2 (activation of keratinocytes) in the Adverse Outcome Pathway for Skin Sensitization. The aim of this pilot study was to share the experience gained during optimization of this method for testing of real-life MD extracts. We have confirmed that the extraction vehicles recommended in ISO10993-12:2021, could be considered for use in the LuSens assay, as they do not interfere with Luciferase induction. However, the preferred use of culture medium with serum as extraction vehicle for cytotoxicity tests was not optimal, as the fetal bovine serum (FBS) content significantly increased the LuSens cell viability, which biased the sensitization results. The study showed the presence of different content of leachable cytotoxic substances in the extracts depending on the type of extraction vehicle, particularly in case of metallic products. Further research will be necessary to identify the optimal extraction conditions for specific materials or devices.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"111 ","pages":"Article 106167"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145309913","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

CYP-mediated metabolic divergence underpins oxoglaucine selectivity: Detoxification in healthy hepatocytes versus mitochondrial apoptosis in hepatocellular carcinoma cypp介导的代谢差异支持氧丙氨酸选择性：健康肝细胞的解毒与肝细胞癌的线粒体凋亡

IF 2.7 3区医学

Toxicology in Vitro Pub Date : 2026-03-01 Epub Date: 2025-10-30 DOI: 10.1016/j.tiv.2025.106170

Pinzheng Li , Hengbin Zhang , Yingchun Chen , Shuanghui Lu , Huidi Jiang , Su Zeng , Hui Zhou

{"title":"CYP-mediated metabolic divergence underpins oxoglaucine selectivity: Detoxification in healthy hepatocytes versus mitochondrial apoptosis in hepatocellular carcinoma","authors":"Pinzheng Li , Hengbin Zhang , Yingchun Chen , Shuanghui Lu , Huidi Jiang , Su Zeng , Hui Zhou","doi":"10.1016/j.tiv.2025.106170","DOIUrl":"10.1016/j.tiv.2025.106170","url":null,"abstract":"<div><div>Oxoglaucine (OXO), an aporphine alkaloid derived from <em>Corydalis yanhusuo</em>, exhibits a broad spectrum of pharmacological activities, including antiviral, antifungal, antiplatelet, and anti-hepatic fibrosis effects, with particularly promising anticancer potential. In this study, we systematically investigated the hepatotoxicity profile and underlying mechanisms of OXO using in vitro models. Dose–response assays revealed that while OXO induced significant cytotoxicity in hepatocytes, primary hepatocytes exhibited markedly reduced sensitivity compared to hepatocellular carcinoma cells at therapeutically relevant concentrations. Mechanistic studies in mouse primary hepatocytes and human primary hepatocytes attributed this selective cytotoxicity to differential cytochrome P450 (CYP) enzyme expression. This finding was functionally validated by the observation that co-treatment with the broad-spectrum CYP inhibitor aminobenzotriazole (ABT) enhanced OXO-induced toxicity in mouse primary hepatocytes and human primary hepatocytes. Regarding its mechanism of toxicity, OXO induced marked cytotoxicity in the HepG2 cell line by triggering mitochondrial-mediated apoptosis, as evidenced by a decreased BCL2/BAX ratio, cytochrome c (CYCS) release, caspase-3 (CASP3) activation, and S-phase cell cycle arrest. Collectively, our findings in HepG2 cells and primary hepatocytes elucidate the role of CYP-mediated metabolism in the selective cytotoxicity of OXO. These findings not only provide crucial mechanistic insights but also support the further development of OXO as a promising candidate for preclinical and clinical evaluation in hepatocellular carcinoma.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"111 ","pages":"Article 106170"},"PeriodicalIF":2.7,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145423432","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