Toxicology in Vitro最新文献

Ultrafine particles induce ferroptosis-like stress features in human dopaminergic LUHMES cells via the p53/xCT/GSH/cGPx4 axis. 超细颗粒通过p53/xCT/GSH/cGPx4轴诱导人多巴胺能LUHMES细胞的铁中毒样应激特征。

IF 2.7 3区医学

Toxicology in Vitro Pub Date : 2026-05-06 DOI: 10.1016/j.tiv.2026.106249

Emma Theerens, Aurélie Jonneaux, Lydia Nikasinovic, Ophélie Simonin, Jean-Christophe Devedjian, Esperanza Perdrix, Véronique Riffault, Laurent Y Alleman, Anne-Sophie Rolland, Guillaume Garçon, David Devos

{"title":"Ultrafine particles induce ferroptosis-like stress features in human dopaminergic LUHMES cells via the p53/xCT/GSH/cGPx4 axis.","authors":"Emma Theerens, Aurélie Jonneaux, Lydia Nikasinovic, Ophélie Simonin, Jean-Christophe Devedjian, Esperanza Perdrix, Véronique Riffault, Laurent Y Alleman, Anne-Sophie Rolland, Guillaume Garçon, David Devos","doi":"10.1016/j.tiv.2026.106249","DOIUrl":"https://doi.org/10.1016/j.tiv.2026.106249","url":null,"abstract":"<p><p>Parkinson's disease (PD) involves progressive loss of dopaminergic neurons in the Substantia Nigra pars compacta, with regulated cell death (RCD) pathways - ferroptosis and apoptosis - contributing to neurodegeneration. Ferroptosis, an iron-dependent form of oxidative cell death, was evaluated here in human dopaminergic neurons exposed to urban industrial ultrafine particles (UFP) from Dunkirk. Differentiated LUHMES cells were treated with 2 or 10 μg/cm<sup>2</sup> UFP for 24 h, for comparison, cells received 5 μM MPP<sup>+</sup>, a reference PD toxin. UFP exposure caused reductions in cytosolic GPx4 and the GSH/GSSG ratio, and increased oxidative damage and electrophilic stress (4-HNE); neither TfR nor DMT1 expression nor ferritin levels changed. Mechanistically, UFP activated p53, downregulating xCT and compromising GSH synthesis, thereby driving ferroptosis-like stress. By contrast, MPP<sup>+</sup> induced more pronounced oxidative imbalance, elevated GSSG, and activated both intrinsic (BAX, caspase-9) and extrinsic (caspase-8) apoptotic cascades. These findings constitute the first evidence that environmentally relevant UFP concentrations trigger ferroptosis-like stress features in human dopaminergic neurons. They implicate chronic UFP inhalation as a potential modifiable risk factor in PD pathogenesis.</p>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":" ","pages":"106249"},"PeriodicalIF":2.7,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147857674","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

Role of CD163 in the mechanism of hydrophilic silica nanoparticle-induced pulmonary fibrosis CD163在亲水二氧化硅纳米颗粒诱导肺纤维化机制中的作用。

IF 2.7 3区医学

Toxicology in Vitro Pub Date : 2026-05-01 Epub Date: 2026-01-24 DOI: 10.1016/j.tiv.2026.106201

Chaoya Ma, Yaotang Deng, Xiao Zhang, Qifeng Wu, Fengrong Lu, Jin Wu, Ying Zhang, Cuiju Wen

{"title":"Role of CD163 in the mechanism of hydrophilic silica nanoparticle-induced pulmonary fibrosis","authors":"Chaoya Ma, Yaotang Deng, Xiao Zhang, Qifeng Wu, Fengrong Lu, Jin Wu, Ying Zhang, Cuiju Wen","doi":"10.1016/j.tiv.2026.106201","DOIUrl":"10.1016/j.tiv.2026.106201","url":null,"abstract":"<div><h3>Objective</h3><div>Silicosis, a progressive pulmonary fibrosis caused by silica dust exposure, remains a global occupational health threat, particularly with the rising use of nano-silica (nano-SiO₂) in industries. This study aims to explore the role of CD163 in pulmonary fibrosis induced by nano-silica (nano-SiO₂), and to evaluate its potential as a diagnostic biomarker by combining clinical analysis of patients with silicosis and in vitro validation models.</div></div><div><h3>Method</h3><div>Gene expression in BALF from stage I silicosis patients was analyzed by PCR. In vitro, THP-1-derived macrophages and MRC-5 fibroblasts were exposed to 100 μg/mL nano-SiO₂ (LC<sub>50</sub>) in mono- and co-culture systems. CD163, CD68, and TNF-α levels were quantified via ELISA and Western blot.</div></div><div><h3>Result</h3><div>In patients, M2 markers (CD163/CD68) were upregulated, while M1 gene (TNF) was downregulated. In vitro, nano-SiO₂ increased macrophage CD163 by 1.7 times (<em>P</em> < 0.05) and decreased TNF-α by 42%. Co-culture further increased CD163 by 2.1 times (<em>P</em> < 0.01), indicating amplified M2 polarization via crosstalk.</div></div><div><h3>Conclusion</h3><div>Nano-SiO₂ drives M2 polarization (CD163↑/TNF-α↓). This finding suggests that CD163 may become one of the potential biomarkers for assessing the risk of pulmonary fibrosis induced by nano-SiO₂, providing important clues for the early warning and mechanism research of silicosis.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"113 ","pages":"Article 106201"},"PeriodicalIF":2.7,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146055005","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

Barrier gel formulations and coated gloves to reduce skin permeation of nicotine and protect against green tobacco sickness 屏障胶配方和涂层手套，以减少皮肤对尼古丁的渗透，防止绿色烟草病。

IF 2.7 3区医学

Toxicology in Vitro Pub Date : 2026-04-01 Epub Date: 2025-12-22 DOI: 10.1016/j.tiv.2025.106192

Abhay U. Andar , Youcheng Liu , Dana C. Hammell , David A. Sterling , Tom Klingner , Mark Tokarski , Mark Boeniger , Audra Stinchcomb

{"title":"Barrier gel formulations and coated gloves to reduce skin permeation of nicotine and protect against green tobacco sickness","authors":"Abhay U. Andar , Youcheng Liu , Dana C. Hammell , David A. Sterling , Tom Klingner , Mark Tokarski , Mark Boeniger , Audra Stinchcomb","doi":"10.1016/j.tiv.2025.106192","DOIUrl":"10.1016/j.tiv.2025.106192","url":null,"abstract":"<div><div>Tobacco harvesting workers may have high levels of skin exposure to nicotine that can lead to green tobacco sickness. Current exposure reduction methods are often infeasible. The purpose of this work was to develop and evaluate the effectiveness of topical barrier gel formulations as a personal protective equipment to reduce nicotine permeation through skin. Four formulations of a barrier gel developed and applied on Yucatan miniature pig skin were tested using a PermeGear flow through <em>in vitro</em> diffusion apparatus. Donor solutions of either L-nicotine or green tobacco leaf extract with and without the use of barrier gel formulations were analyzed over a 24 h exposure period. High pressure liquid chromatography was used to quantify the nicotine content in the receiver compartment. Gloves coated with a barrier gel formulation were also tested. The best barrier gel formulations reduced <em>in vitro</em> skin permeation of nicotine by 97.6 % from L-nicotine, by 64.0 % from green tobacco leaf extract, and by 86.6 % from green tobacco leaf extract for gardening gloves coated with the barrier gel. The barrier gel is effective in reducing skin permeation of nicotine <em>in vitro</em> and might have greater preventive capabilities at environmental exposure levels of nicotine during tobacco harvesting.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"112 ","pages":"Article 106192"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145829090","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

Using a reconstructed human vaginal epithelium model to assess irritation: A proof-of-concept study supporting regulatory qualification of the method for use with personal lubricants 使用重建的人阴道上皮来评估刺激：一项概念验证研究，支持该方法用于个人润滑剂的监管资格。

IF 2.7 3区医学

Toxicology in Vitro Pub Date : 2026-04-01 Epub Date: 2026-01-16 DOI: 10.1016/j.tiv.2026.106198

Jessica Perrin , Gertrude-Emilia Costin , Seyoum Ayehunie , Helena Kandárová , Timothy Landry , Jeffrey Brown , Amy J. Clippinger

{"title":"Using a reconstructed human vaginal epithelium model to assess irritation: A proof-of-concept study supporting regulatory qualification of the method for use with personal lubricants","authors":"Jessica Perrin , Gertrude-Emilia Costin , Seyoum Ayehunie , Helena Kandárová , Timothy Landry , Jeffrey Brown , Amy J. Clippinger","doi":"10.1016/j.tiv.2026.106198","DOIUrl":"10.1016/j.tiv.2026.106198","url":null,"abstract":"<div><div>Consumers tend to think of personal lubricants as personal care products or cosmetics that are not tested using animals, but the regulatory classification and hence the testing requirements for these products vary by country. For example, in the United States, regulations and guidance classify personal lubricants as medical devices, for which manufacturers must perform a rabbit vaginal irritation (RVI) test as part of a typical safety assessment submitted to the Food and Drug Administration (FDA). This publication discusses replacing the RVI with an <em>in vitro</em> reconstructed human vaginal epithelium (RHVE) test method, which uses the EpiVaginal model to assess the irritation potential of personal lubricants. The proof-of-concept studies presented here indicate that this <em>in vitro</em> test method can rank water-based personal lubricants by vaginal irritation potential. Scientific confidence in this test method is evaluated based on an established framework that considers the method's context of use, human biological relevance, technical characterization, data integrity and transparency, and independent review. A proposed workplan aims to further develop and qualify the <em>in vitro</em> test method for regulatory acceptance in assessing vaginal irritation of personal lubricants, and expanding its use to other products.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"112 ","pages":"Article 106198"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145999714","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

Alternatives to animal testing in cosmetic products: A patent applications review and future perspectives 化妆品动物试验的替代方案：专利申请审查和未来展望。

IF 2.7 3区医学

Toxicology in Vitro Pub Date : 2026-04-01 Epub Date: 2025-12-03 DOI: 10.1016/j.tiv.2025.106187

Carine Cassimiro Cedrola, Clara Cassimiro Cedrola, Ana Cláudia Chagas de Paula, Juliana de Carvalho da Costa, Fernanda Maria Pinto Vilela

{"title":"Alternatives to animal testing in cosmetic products: A patent applications review and future perspectives","authors":"Carine Cassimiro Cedrola, Clara Cassimiro Cedrola, Ana Cláudia Chagas de Paula, Juliana de Carvalho da Costa, Fernanda Maria Pinto Vilela","doi":"10.1016/j.tiv.2025.106187","DOIUrl":"10.1016/j.tiv.2025.106187","url":null,"abstract":"<div><div>Ethical concerns, high costs, and scientific limitations associated with animal testing have accelerated the search for alternative methods to evaluate the safety and efficacy of topical cosmetic formulations. This study provides a comprehensive analysis of the global patent landscape related to non-animal testing approaches for skin care products, focusing on filings from January 2015 to March 2025, indexed in the Espacenet database. From 470 patent applications initially screened, 23 met the predefined inclusion and exclusion criteria and were selected for in-depth analysis. Key innovations include 3D epidermal models featuring melanocytes, hair follicles, and sebaceous glands; advanced microfluidic chips, and enzyme-based chemical toxicity assays. Although supported by regulatory frameworks, challenges persist regarding standardization, reproducibility, and the ethical sourcing of human tissue. This patent application review reveals a clear shift toward advanced 3D models and organ-on-a-chip technologies that better replicate the complexity of human skin physiology. The trends observed indicate that alternative methods to animal testing are not only an ethical necessity but are also becoming a technological reality, offering more predictive, reliable, and efficient strategies for safety assessment.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"112 ","pages":"Article 106187"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145688740","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

Interactions of neocryptotanshinone and human cytochrome P450 in silico and in vitro 新隐丹参酮与人细胞色素P450的相互作用。

IF 2.7 3区医学

Toxicology in Vitro Pub Date : 2026-04-01 Epub Date: 2025-12-17 DOI: 10.1016/j.tiv.2025.106191

Xiu Chen , Xiaoyi Pan , Jieping Zhao , Huihui Jin , Hengbin Zhang , Yongbiao Song , Hui Zhou , Jianbiao Yao , Huidi Jiang

{"title":"Interactions of neocryptotanshinone and human cytochrome P450 in silico and in vitro","authors":"Xiu Chen , Xiaoyi Pan , Jieping Zhao , Huihui Jin , Hengbin Zhang , Yongbiao Song , Hui Zhou , Jianbiao Yao , Huidi Jiang","doi":"10.1016/j.tiv.2025.106191","DOIUrl":"10.1016/j.tiv.2025.106191","url":null,"abstract":"<div><div>Neocryptotanshinone (NCTS), an ingredient of Salviae Miltiorrhizae Radix et Rhizoma, is a promising compound for development since it exhibits various pharmacological effects including hypoglycemic and anti-inflammatory activities. In this study, we aimed to elucidate the interactions between NCTS and cytochrome P450s (CYPs), including the CYP-mediated NCTS metabolism and NCTS-induced CYP regulation. The results revealed that NCTS was mainly metabolized by CYPs in human liver microsomes (HLMs), and CYP2C8 and 2C9 were identified as the main CYPs involved; the relative contributions of CYP2C8 and 2C9 were 35 % and 65 %, respectively, after normalization of individual CYP abundance in the human liver. Meanwhile, NCTS weakly inhibited CYP1A2, 2C8, and 2C9, with IC<sub>50</sub> > 30 μM. In addition, NCTS induced CYP2B6 and CYP3A4 expression in human primary hepatocytes, and the underlying mechanism was found by the activation of the pregnane X receptor (PXR) <em>vis</em> reporter gene assay. Molecular docking of NCTS and CYPs, PXR confirmed these results. Our study sheds light on the interactions of NCTS with CYPs and provides useful information for predicting potential drug-drug interactions for NCTS, which will be helpful for NCTS development and clinical utilization of drugs containing NCTS.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"112 ","pages":"Article 106191"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145795585","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 cyanobacterial metabolites and their mixtures on biomarkers of oxidative stress in RTgill-W1 cells 蓝藻代谢产物及其混合物对RTgill-W1细胞氧化应激生物标志物的影响

IF 2.7 3区医学

Toxicology in Vitro Pub Date : 2026-04-01 Epub Date: 2026-01-06 DOI: 10.1016/j.tiv.2026.106195

Adam Bownik, Barbara Pawlik-Skowrońska

{"title":"Effects of cyanobacterial metabolites and their mixtures on biomarkers of oxidative stress in RTgill-W1 cells","authors":"Adam Bownik, Barbara Pawlik-Skowrońska","doi":"10.1016/j.tiv.2026.106195","DOIUrl":"10.1016/j.tiv.2026.106195","url":null,"abstract":"<div><div>The aim of our investigation was to determine the effects of seven cyanobacterial metabolites microcystin-LR (MC-LR), anabaenopeptin-A (ANA-A), cylindrospermopsin (CYL), anabaenopeptin-B (ANA-B) aeruginosin 98 A (AER-A), aeruginosin 98B (AER-B), microginin-FR1 (MG-FR1) and their mixtures on common indicators of oxidative stress in RTgill-W1cells. The cells were exposed to the metabolites at various concentrations and the following parameters were determined after 48 h: catalase (CAT) activity, lipid peroxidation (LPO), total nitric oxide (NO) level and superoxide (SOD) dismutase activity. Data were analyzed with the use of one-way ANOVA (<em>N</em> = 3) and Dunnett's test. We found that all single tested metabolites increased but CYL decreased CAT activity. Mixtures had stimulatory effect, however antagonistic interactions were found in the binary and ternary mixtures. No lipid peroxidation occurred in the cells exposed to any of the tested variant. Only AER-A increased NO level, however the rest of both single metabolites at highest concentrations (1004 nM) and mixtures reduced the level of this parameter. Only ANA-B inhibited SOD activity at the highest concentration, however no alterations were found in the cells exposed to binary or ternary mixtures. The study showed that cyanobacterial metabolites may induce oxidative stress in fish gill cells, however effects are dependent on type of a metabolite and concentration of a component in mixtures. On the basis of antagonistic interactions in ternary mixture it may be hypothesized that during natural exposure components of mixtures may reciprocally mitigate their effects.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"112 ","pages":"Article 106195"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925742","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

Cisplatin adducts at DNA or RNA do not affect their cellular isolation efficiencies using column-based kits or manual Trizol-based purification methods DNA或RNA上的顺铂加合物使用柱基试剂盒或手动trizol基纯化方法不影响其细胞分离效率。

IF 2.7 3区医学

Toxicology in Vitro Pub Date : 2026-04-01 Epub Date: 2025-12-06 DOI: 10.1016/j.tiv.2025.106188

Ketaki Sandu, Dirk Theile

{"title":"Cisplatin adducts at DNA or RNA do not affect their cellular isolation efficiencies using column-based kits or manual Trizol-based purification methods","authors":"Ketaki Sandu, Dirk Theile","doi":"10.1016/j.tiv.2025.106188","DOIUrl":"10.1016/j.tiv.2025.106188","url":null,"abstract":"<div><div>In experimental toxicology, evaluating cisplatin adducts at DNA or RNA is often required but can be complicated by methodological aspects. For instance, the cross-linking might affect the nucleic acid isolation efficiencies, which in turn can be influenced by the purification approach. Two cancer cell lines were cisplatin treated and DNA/RNA were isolated using manual Trizol-based protocols or column-based kits. Platinum levels at DNA/RNA were evaluated by atomic absorption spectroscopy.</div><div>For RNA, the manual purification yielded higher concentrations than the kit for both cisplatin-treated and non-treated samples. RNA platination was identical for both isolation approaches. For DNA, the manual method can yield lower concentrations from cisplatin-treated cells, likely reflecting diminished solubility of cross-linked DNA. DNA platination levels again were identical with both isolation methods.</div><div>Because DNA isolation is less efficient than RNA isolation, platinum-DNA adduct quantification is difficult when DNA yields are low or cells were exposed to low cisplatin concentrations. However, DNA platination can be estimated by the platination degree of RNA because platination of both nucleic acids agreed well and RNA was always isolated very efficiently.</div><div>In summary: First, manual purification and column-based kits can yield unequal nucleic acid concentrations, and RNA is more efficiently purified than DNA. Second, column-based kits remain practical because platination does not affect isolation efficiency. Third, when DNA platination is not quantifiable (low yield, small sample volumes), RNA platination is a good proxy.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"112 ","pages":"Article 106188"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145710433","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

Quercetin mitigates pro-inflammatory effects of polyvinylpyrrolidone-coated silver nanoparticles on human intestinal epithelial cells 槲皮素减轻聚乙烯吡咯烷酮包被银纳米颗粒对人肠上皮细胞的促炎作用。

IF 2.7 3区医学

Toxicology in Vitro Pub Date : 2026-04-01 Epub Date: 2025-11-22 DOI: 10.1016/j.tiv.2025.106176

Adelaide Sousa , Inês Santos , Rui Fernandes , Sofia Pacheco , Félix Carvalho , Eduarda Fernandes , Marisa Freitas

{"title":"Quercetin mitigates pro-inflammatory effects of polyvinylpyrrolidone-coated silver nanoparticles on human intestinal epithelial cells","authors":"Adelaide Sousa , Inês Santos , Rui Fernandes , Sofia Pacheco , Félix Carvalho , Eduarda Fernandes , Marisa Freitas","doi":"10.1016/j.tiv.2025.106176","DOIUrl":"10.1016/j.tiv.2025.106176","url":null,"abstract":"<div><div>Extended oral intake of silver nanoparticles (AgNP) may result in significant exposure of intestinal cells, which could trigger intestinal inflammation, an effect that requires deep comprehension and the development of mitigation measures. This study aimed to investigate the potential pro-inflammatory effects of polyvinylpyrrolidone (PVP)-coated AgNP with two different sizes (5 and 50 nm) on human intestinal epithelial C2BBe1 cells, as well as the potential mitigation effects of quercetin, a flavonoid with acknowledged antioxidant and anti-inflammatory potential. The pro-inflammatory effects of PVP-AgNP on several proteins related to the intestinal inflammatory response, as well as on <sup>●</sup>NO production and cytokine production, were investigated. PVP-AgNP exposure caused cellular stress and damage, as evidenced by a reduction in cellular metabolic activity, ultrastructural changes, and loss of viability. The present study also found that 5 nm PVP-AgNP triggered inflammation through the p65-induced NF-κB pathway and reduced p-Nrf2 expression, while 50 nm PVP-AgNP activated the IκBα-induced NF-κB pathway and elevated COX-2 levels. Both sizes induced an increase of PGE<sub>2</sub> levels and IL-8 production, with only 5 nm PVP-AgNP increasing IL-6. The harmful effects of PVP-AgNP were effectively mitigated by quercetin, which highlights the potential of this flavonoid to modulate the respective potential damage at the intestinal level.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"112 ","pages":"Article 106176"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145598126","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

Dual effects of metformin and resveratrol on compromising viability of endometrial cancer cells 二甲双胍和白藜芦醇对子宫内膜癌细胞生存能力的双重影响

IF 2.7 3区医学

Toxicology in Vitro Pub Date : 2026-04-01 Epub Date: 2026-01-06 DOI: 10.1016/j.tiv.2026.106194

Henrique Leal de Oliveira , Sara Hartke , Victória Borgmann A. de Souza , Carolina Vaccari Batista , Gabriela Pasqualim , Vânia Marisia Santos Fortes dos Reis , Edison Capp , Leo Anderson Meira Martins , Ilma Simoni Brum

{"title":"Dual effects of metformin and resveratrol on compromising viability of endometrial cancer cells","authors":"Henrique Leal de Oliveira , Sara Hartke , Victória Borgmann A. de Souza , Carolina Vaccari Batista , Gabriela Pasqualim , Vânia Marisia Santos Fortes dos Reis , Edison Capp , Leo Anderson Meira Martins , Ilma Simoni Brum","doi":"10.1016/j.tiv.2026.106194","DOIUrl":"10.1016/j.tiv.2026.106194","url":null,"abstract":"<div><div>Raising of mitogenic and anti-apoptotic agents – such as insulin, insulin-like growth factor type 1, and estrogen – during obesity and diabetes mellitus (types 1 and 2) favors the endometrial cancer (EC) development. Metformin, commonly used for treating type 2 diabetes, and resveratrol, a natural polyphenol, can both decrease cancer cell proliferation by modulating the PI3K/Akt/mTOR pathway. We evaluate the effects of metformin and/or resveratrol in an <em>in vitro</em> model of human type 1 endometrioid EC. Ishikawa cells were treated with 0.1 to 50 mM of metformin and/or 0.1 to 75 μM of resveratrol from 24 h to 72 h. Analyses assessed cell viability, cytotoxicity, caspases activation, mitochondrial function, cellular death, cell cycle, and the PI3K/Akt/mTOR pathway gene expression. <em>In-silico</em> analysis was conducted using Cytoscape. Metformin induced mitochondrial swelling, caspase-mediated apoptosis, and cell cycle arrest. Resveratrol decreased mitochondrial mass, cytotoxicity, and induced cell cycle arrest. Combined treatment with the highest concentrations reduced mitochondrial activity, cytotoxicity, and caspase activation while maintaining apoptotic features and cell cycle arrest. Resveratrol attenuated the toxic effects of metformin but it could be inducing a caspase-independent cell death in co-treated cells. Although <em>in-silico</em> analysis suggested potential molecular targets and interconnected mechanisms, lower concentrations did not alter PI3K/Akt/mTOR gene expression.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"112 ","pages":"Article 106194"},"PeriodicalIF":2.7,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925598","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