Toxicology in Vitro最新文献_第3页

Genotoxicity of putrescine and its effects on gene expression in HepG2 cell line 腐胺的遗传毒性及其对HepG2细胞基因表达的影响。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-03-12 DOI: 10.1016/j.tiv.2025.106048

Franco Dani Campos-Pereira , Letícia Rocha Gonçalves, Raquel Vaz Hara Jardim, Letícia Bulascochi Cagnoni, Karen C.M. Moraes, Maria Aparecida Marin-Morales

{"title":"Genotoxicity of putrescine and its effects on gene expression in HepG2 cell line","authors":"Franco Dani Campos-Pereira , Letícia Rocha Gonçalves, Raquel Vaz Hara Jardim, Letícia Bulascochi Cagnoni, Karen C.M. Moraes, Maria Aparecida Marin-Morales","doi":"10.1016/j.tiv.2025.106048","DOIUrl":"10.1016/j.tiv.2025.106048","url":null,"abstract":"<div><div>Decomposing bodies release necro-leachate, a toxic fluid containing harmful compounds such as biogenic amines. This study investigated the genotoxic effects of the different concentrations (0.5, 1.4, 2.3, 3.2 mM) of bioamine putrescine on HepG2 cells using the comet assay, the micronucleus test, and gene expression analysis. The results were compared to negative control and indicated significant DNA damage in the comet assay highlighting tail DNA intensity that exhibited significant differences across all tested concentrations (0.5 = 192 %, 1.4 = 189 %, 2.3 = 208 %, 3.2 = 132 %). The micronucleus test revealed a significant increase in micronuclei for concentrations 0.5 (193 %), 1.4 (229 %), 2.3 (206 %); nuclear buds 3.2 (173 %); chromosomal bridges 3.2 (735 %). Furthermore, genes linked to oxidative stress and DNA damage exhibited statistically significant expression alterations. These findings suggest that putrescine has genotoxic potential in human-derived HepG2 cells, raising concerns about cemetery contaminants' occupational and environmental risks. This study is the first to assess putrescine's toxicity as an environmental pollutant, as previous research has mainly focused on its role in the food sector. These insights highlight the potential threats necro-leachate poses to environmental health, emphasizing the need for further research on cemetery pollution.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"106 ","pages":"Article 106048"},"PeriodicalIF":2.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631046","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

Minimum information for studies of extracellular vesicles (MISEV) as toolbox for rigorous, reproducible and homogeneous studies on extracellular vesicles 细胞外囊泡研究的最小信息（MISEV）是细胞外囊泡严格、可重复和均匀研究的工具箱

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-03-10 DOI: 10.1016/j.tiv.2025.106049

Julien Saint-Pol, Maxime Culot

{"title":"Minimum information for studies of extracellular vesicles (MISEV) as toolbox for rigorous, reproducible and homogeneous studies on extracellular vesicles","authors":"Julien Saint-Pol, Maxime Culot","doi":"10.1016/j.tiv.2025.106049","DOIUrl":"10.1016/j.tiv.2025.106049","url":null,"abstract":"<div><div>Studies based on extracellular vesicles (EVs) have been multiplying exponentially for almost two decades, since they were first identified as vectors of cell-cell communication. However, several of these studies display a lack of rigor in EVs characterization and isolation, without discriminating between the different EV populations, thus generating conflicting and unreproducible results. There is therefore a strong need for standardization and guidelines to conduct studies that are rigorous, transparent, reproducible and comply with certain nomenclatures concerning the type of EVs used. The International Society for Extracellular Vesicles (ISEV) published the Minimum Information for Studies of Extracellular Vesicles (MISEV) in 2014, updating it in 2018 and 2023 to reflect different study contexts and technical advancements. The primary objective of this review is to inform future authors about EVs, including their history, nomenclature, and technical recommendations for the for isolation and functionality analysis for conducing EV-based studies according to current standards. Additionally, it aims to inform reviewers about the key parameters required for characterizing EV preparations.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"106 ","pages":"Article 106049"},"PeriodicalIF":2.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143611146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MEK1 inhibition ameliorates mitochondrial-dependent apoptosis induced by deltamethrin in mouse hippocampal neuron HT22 cells 抑制 MEK1 可改善溴氰菊酯诱导的小鼠海马神经元 HT22 细胞线粒体依赖性凋亡。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-03-07 DOI: 10.1016/j.tiv.2025.106047

Lexing Wei , Yang Chen , Minjia Wu , Peixuan Ma , Huan Wang , Yueming Jiang , Michael Aschner , Jing Zhou , Guodong Lu , Lina Zhao , Xiaowei Huang

{"title":"MEK1 inhibition ameliorates mitochondrial-dependent apoptosis induced by deltamethrin in mouse hippocampal neuron HT22 cells","authors":"Lexing Wei , Yang Chen , Minjia Wu , Peixuan Ma , Huan Wang , Yueming Jiang , Michael Aschner , Jing Zhou , Guodong Lu , Lina Zhao , Xiaowei Huang","doi":"10.1016/j.tiv.2025.106047","DOIUrl":"10.1016/j.tiv.2025.106047","url":null,"abstract":"<div><div>Deltamethrin (DM), a widely used pyrethroid insecticide, has been increasingly recognized as a risk factor for neurodegeneration. However, the underlying mechanism is still far from clear. In this study, we investigated whether MEK1 is involved in DM-induced neurotoxicity and mediated mitochondrial-dependent apoptosis. In mouse hippocampal neuron HT22 cells model, DM (2,10,50 μM) dose-dependently increased apoptotic cells rate and impaired mitochondrial membrane potential (MMP), as well as significantly upregulated of apoptotic related proteins Bax, cytochrome <em>c</em> (Cyt-c) and Caspase-3 were observed. RNA-sequencing analysis further revealed that the MEK/ERK signal pathway was remarkably enriched and activated after DM exposure. In particularly, upregulation of MEK1, other than ERK1/2, was detected at both transcriptional and translational levels. Inhibition of MEK1 can effectively result in the recovery of mitochondrial morphology and MMP in DM-treated HT22 cells. And that further alleviated apoptosis by reversing the overexpression of Bax, Cyt-c and Caspase-3. Collectively, these findings demonstrate the critical role of MEK1 in regulating mitochondrial-dependent apoptosis induced by DM, providing a novel understanding of the neurotoxicity of DM.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"106 ","pages":"Article 106047"},"PeriodicalIF":2.6,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143588223","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

Validation of a new 3D epidermis model for the SENS-IS assay to evaluate skin sensitization potency of chemicals 一种新的3D表皮模型的验证，用于SENS-IS测定，以评估化学物质的皮肤致敏效力

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-03-05 DOI: 10.1016/j.tiv.2025.106039

Françoise Cottrez, Elodie Boitel, Essia Sahli, Hervé Groux

{"title":"Validation of a new 3D epidermis model for the SENS-IS assay to evaluate skin sensitization potency of chemicals","authors":"Françoise Cottrez, Elodie Boitel, Essia Sahli, Hervé Groux","doi":"10.1016/j.tiv.2025.106039","DOIUrl":"10.1016/j.tiv.2025.106039","url":null,"abstract":"<div><div>In vitro methods for evaluating skin sensitization are advancing as ethical alternatives to animal testing. The SENS-IS assay, based on genomic profiling, relies on robust biological models like 3D reconstructed human epidermis (RHE). The Rhe model from Episkin was typically used to performed the SENS-IS assay. This study validates the Skin+ model as an alternative to the established Episkin model in the SENS-IS assay.</div><div>We tested 19 proficiency chemicals categorized by human and LLNA potency and compared results between Skin+ and Episkin. The Skin+ model demonstrated over 93 % intra- and inter-batch reproducibility, closely matching Episkin's performance. Additionally, barrier function tests and gene expression analyses confirmed the consistency of the Skin+ model in response to SLS, TNBS, and DMSO treatments.</div><div>The Skin+ model proved to be a reliable and reproducible alternative to the EpiSkin model, maintaining strong barrier integrity and delivering comparable sensitization predictions. This validation broadens the options for laboratories and industries seeking versatile 3D RHE models for in vitro skin sensitization testing, supporting the transition to more ethical and precise methods.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"106 ","pages":"Article 106039"},"PeriodicalIF":2.6,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143577558","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

Glutaraldehyde-crosslinked Naringenin-loaded Albumin Nanoparticles (GNANPs) induce antimicrobial properties and apoptosis in gastric cancer cells 戊二醛交联柚皮素负载白蛋白纳米颗粒（GNANPs）诱导胃癌细胞的抗菌特性和凋亡。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-03-02 DOI: 10.1016/j.tiv.2025.106037

Murugan Alwarkurichi Munusamy , Muruganantham Bharathi , Abdullah A. Alarfaj , Samer Hasan Hussein-Al-Ali , Ravichandran Nagaiya , Sarathbabu Subbarayan

{"title":"Glutaraldehyde-crosslinked Naringenin-loaded Albumin Nanoparticles (GNANPs) induce antimicrobial properties and apoptosis in gastric cancer cells","authors":"Murugan Alwarkurichi Munusamy , Muruganantham Bharathi , Abdullah A. Alarfaj , Samer Hasan Hussein-Al-Ali , Ravichandran Nagaiya , Sarathbabu Subbarayan","doi":"10.1016/j.tiv.2025.106037","DOIUrl":"10.1016/j.tiv.2025.106037","url":null,"abstract":"<div><div>An assessment of the anticancer activity of Glutaraldehyde-crosslinked Naringenin-loaded Albumin Nanoparticles (GNANPs) against gastric cancer cells was the purpose of this study. The increasing prevalence of gastric cancer and the limitations of conventional therapies necessitate novel approaches that combine targeted drug delivery with therapeutic efficacy. Several techniques were used to characterize the synthesized GNANPs, including UV–visible spectroscopy, X-ray diffractometer (XRD), scanning electron microscope (SEM), transmission electron microscope (TEM), Fourier transform infrared (FT-IR), dynamic light scattering (DLS), and photoluminescence (PL). They were evaluated for their antimicrobial properties, cytotoxicity, ROS accumulation, apoptotic activity, and oxidative stress markers against AGS cells. The characterization analyses indicated the existence of Glutaraldehyde-crosslinked Naringenin-loaded Albumin Nanoparticles with an oval-shaped morphology and an average particle size of 127.80 nm. The existence of several elements and functional groups in the GNANPs was also detected using EDX and FT-IR analyses, respectively. The synthesized GNANPs have shown exceptional antibacterial activities by effectively inhibiting the growth of several infections. The treatment of GNANPs efficiently inhibited the growth of AGS cells. Fluorescence staining studies showed increased apoptosis and oxidative stress markers in AGS cells treated with synthesized Glutaraldehyde-crosslinked Naringenin-loaded Albumin Nanoparticles, indicating their potential as a viable cancer treatment option.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"106 ","pages":"Article 106037"},"PeriodicalIF":2.6,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558873","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 culture media on gene expression in reconstructed human epidermis and THP-1 monocytes for skin sensitization evaluation in co-culture systems 培养基对重建人表皮及共培养系统中THP-1单核细胞基因表达的影响

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-02-28 DOI: 10.1016/j.tiv.2025.106035

Y. Sugimoto-Sawada , M. Yamashiro , M. Kono , H. Ikeda , H. Itagaki , K. Iijima

{"title":"Effects of culture media on gene expression in reconstructed human epidermis and THP-1 monocytes for skin sensitization evaluation in co-culture systems","authors":"Y. Sugimoto-Sawada , M. Yamashiro , M. Kono , H. Ikeda , H. Itagaki , K. Iijima","doi":"10.1016/j.tiv.2025.106035","DOIUrl":"10.1016/j.tiv.2025.106035","url":null,"abstract":"<div><div>Co-culture with reconstituted epidermis formed by normal human epidermal keratinocytes (RhE) increases the expression of the skin sensitization markers CD54 and CD86 on the human monocytic leukemia cell line THP-1 without chemicals. Therefore, we investigated the effects of culture media [RPMI1640 for RhE; keratinization induction (KI) medium for THP-1], co-culture, and the responses to the skin sensitizer 2,4-dinitrochlorobenzene (DNCB) on gene expression in mono- and cocultures of RhE and THP-1 cells. Microarray and pathway analyses revealed that in mono-RhE, RPMI medium induced epidermal differentiation-related genes, whereas in monoculture THP-1 cells, KI medium upregulated inflammation-related genes. Surprisingly, the medium composition had a more significant impact than co-culture in both cells. However, crosstalk between RhE and THP-1 cells was observed upon DNCB exposure by comparing the differentially expressed gene sets. DNCB-treated THP-1 cells showed increased expression of <em>NR4A1</em>, <em>NR4A2</em>, <em>NR4A3</em>, <em>SIK1</em>, and <em>HMOX1</em> in co-culture than in monoculture, and these gene expression patterns were confirmed by real-time RT-PCR. It has been suggested that danger signals from RhE, in response to DNCB, enhance the expression of these genes in THP-1 cells. We clarified the effects of the medium and co-culture and proposed these five genes as potential markers for skin sensitization evaluation.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"106 ","pages":"Article 106035"},"PeriodicalIF":2.6,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536742","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

Cross-species comparisons of plasma binding and considerations for data evaluation 血浆结合的跨物种比较和数据评估的考虑。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-02-27 DOI: 10.1016/j.tiv.2025.106036

Scott G. Lynn , Irvin R. Schultz , Sharlene R. Matten , Purvi R. Patel , Scott L. Watson , Yun Lan Yueh , Sherry R. Black , Barbara A. Wetmore

{"title":"Cross-species comparisons of plasma binding and considerations for data evaluation","authors":"Scott G. Lynn , Irvin R. Schultz , Sharlene R. Matten , Purvi R. Patel , Scott L. Watson , Yun Lan Yueh , Sherry R. Black , Barbara A. Wetmore","doi":"10.1016/j.tiv.2025.106036","DOIUrl":"10.1016/j.tiv.2025.106036","url":null,"abstract":"<div><div>The US Environmental Protection Agency is increasingly employing new approach methods (NAMs), including in vitro plasma binding and hepatocyte clearance experiments to collect chemical-species specific data. This paper presents data from plasma binding experiments using rapid equilibrium dialysis (RED) devices and plasma from humans, rats, and rainbow trout with a 4-h incubation time. A total of 54 chemicals, utilizing two concentrations, were tested across the three species resulting in 238 chemical-species specific datasets. Mass balance controls for chemical plasma stability and dialysis system recovery were used to evaluate the datasets and almost 40 % of the datasets (92/238 datasets) produced quantitative measurements. Cross-species comparisons and evaluations of the impact of physicochemical properties on chemical-assay performance were also evaluated. Comparisons of human-rat plasma binding revealed rat plasma generally demonstrated higher <em>f</em><sub><em>up</em></sub> values for chemicals than human. While <em>f</em><sub><em>up</em></sub> values in trout plasma were frequently lower than rat or human plasma. A comparison with literature data was performed and correlations between plasma binding, expressed as fraction unbound in plasma (<em>f</em><sub><em>up</em></sub>), and log K<sub>ow</sub> across all three species indicate that the strongest relationship occurs at log K<sub>ow</sub> values between 1.5 and 4. The obtained datasets exhibited a wide range of behaviors, emphasizing the need for a robust approach to data quality assessment. The broader analysis of <em>f</em><sub><em>up</em></sub> values indicates that chemicals with log K<sub>ow</sub> > 4.5 will be highly bound (<em>f</em><sub><em>up</em></sub> ≤ 0.0001), difficult to measure, and have low reproducibility across laboratories, suggesting that use of different methods may be needed across different physicochemical properties.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"106 ","pages":"Article 106036"},"PeriodicalIF":2.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538177","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

Reexamining the acute toxicity of chloropicrin: Comprehensive estimation using in silico methods 氯霉素急性毒性的再检验：计算机方法的综合评价

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-02-26 DOI: 10.1016/j.tiv.2025.106033

Maciej Noga , Kamil Jurowski

{"title":"Reexamining the acute toxicity of chloropicrin: Comprehensive estimation using in silico methods","authors":"Maciej Noga , Kamil Jurowski","doi":"10.1016/j.tiv.2025.106033","DOIUrl":"10.1016/j.tiv.2025.106033","url":null,"abstract":"<div><div>Chloropicrin, historically infamous as a chemical warfare agent during World War I, has recently resurfaced in global conflicts, prompting a reevaluation of its acute toxicological significance. This study addresses the historical knowledge gap surrounding chloropicrin by employing <em>in silico</em> toxicology methods to estimate toxicophores and predict acute toxicity across various exposure routes. Allegations of its use in recent conflicts necessitate a deeper understanding of its toxicological profile, particularly in modern warfare scenarios. Qualitative analysis (STopTox and admetSAR) revealed chloropicrin to be toxic for oral, dermal, and inhalation administration, with the nitro group attached to the carbon atom identified as a significant contributor to its toxic profile. Quantitative <em>in silico</em> estimates, using multiple methods (TEST, ProTox-II, ADMETlab, ACD/Labs Percepta and QSAR Toolbox), indicated t-LD<sub>50</sub> values of 48.71 mg/kg bw for oral exposure, 130.16 mg/kg bw for dermal exposure, and an inhalation t-LC<sub>50</sub> of 0.022 mg/L. However, method inconsistencies and variability in dose conversion guidance highlight the importance of a cautious approach to interpreting results. Furthermore, the study explores the potential of <em>in silico</em> methods to reduce reliance on animal testing, providing a more efficient and humane alternative for toxicity assessments. The findings contribute to a comprehensive understanding of chloropicrin's acute toxicity, emphasising the relevance of <em>in silico</em> methods in guiding future toxicological studies and informing safety assessments in agricultural and wartime scenarios.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"105 ","pages":"Article 106033"},"PeriodicalIF":2.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520442","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

A perfused iPSC-derived proximal tubule model for predicting drug-induced kidney injury 灌注ipsc衍生近端小管模型预测药物性肾损伤。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-02-26 DOI: 10.1016/j.tiv.2025.106038

Michelle Lechtenberg , Coraline Chéneau , Kevin Riquin , Leopold Koenig , Carlos Mota , Franck Halary , Eva-Maria Dehne

{"title":"A perfused iPSC-derived proximal tubule model for predicting drug-induced kidney injury","authors":"Michelle Lechtenberg , Coraline Chéneau , Kevin Riquin , Leopold Koenig , Carlos Mota , Franck Halary , Eva-Maria Dehne","doi":"10.1016/j.tiv.2025.106038","DOIUrl":"10.1016/j.tiv.2025.106038","url":null,"abstract":"<div><div>The kidney is frequently exposed to high levels of drugs and their metabolites, which can injure the kidney and the proximal tubule (PT) in particular. In order to detect nephrotoxicity early during drug development, relevant <em>in vitro</em> models are essential. Here, we introduce a robust and versatile cell culture insert-based iPSC-derived PT model, which can be maintained in a microphysiological system for at least ten days. We demonstrate the model's ability to predict drug-induced PT injury using polymyxin B, cyclosporin A, and cisplatin, and observe that perfusion distinctly impacts our model's response to xenobiotics. We observe that the upregulation of metallothioneins that is described <em>in vivo</em> after treatment with these drugs is reliably detected in dynamic, but not static <em>in vitro</em> PT models. Finally, we use our model to alleviate polymyxin-induced nephrotoxicity by supplementing the antioxidant curcumin. Together, these findings illustrate that our perfused iPSC-derived PT model is versatile and well-suited for <em>in vitro</em> studies investigating nephrotoxicity and its prevention. Reliable and user-friendly <em>in vitro</em> models like this enable the early detection of nephrotoxic potential, thereby minimizing adverse effects and reducing drug attrition.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"105 ","pages":"Article 106038"},"PeriodicalIF":2.6,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143532174","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

An interdisciplinary approach to assessing the toxicity reduction of cerium oxide nanoparticles coated with polyethylene glycol and polyvinylpyrrolidone polymers: An in vitro study 一种跨学科的方法来评估用聚乙二醇和聚乙烯吡咯烷酮聚合物包覆的氧化铈纳米颗粒的毒性降低：一项体外研究。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2025-02-21 DOI: 10.1016/j.tiv.2025.106022

Mohadeseh Soltani , Motahareh Soltani , Somayyeh Karami-Mohajeri , Alireza Mohadesi , Mehdi Ranjbar , Zohreh Oghabian , Omid Mehrpour , Farshid Khosravi

{"title":"An interdisciplinary approach to assessing the toxicity reduction of cerium oxide nanoparticles coated with polyethylene glycol and polyvinylpyrrolidone polymers: An in vitro study","authors":"Mohadeseh Soltani , Motahareh Soltani , Somayyeh Karami-Mohajeri , Alireza Mohadesi , Mehdi Ranjbar , Zohreh Oghabian , Omid Mehrpour , Farshid Khosravi","doi":"10.1016/j.tiv.2025.106022","DOIUrl":"10.1016/j.tiv.2025.106022","url":null,"abstract":"<div><h3>Objective</h3><div>This study combines toxicology, analytical chemistry, and nanotechnology to develop cerium oxide nanoparticles, both uncoated and coated with Polyethylene Glycol and Polyvinylpyrrolidone polymers. The objective is to assess their toxicity reduction using cell-based assays.</div></div><div><h3>Methods</h3><div>Nanoparticles were synthesized using the co-precipitation technique. Scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS) were employed to characterize their properties. The MTT assay evaluated cell viability, whereas reactive oxygen species and LPO assays were used to quantify oxidative stress.</div></div><div><h3>Findings</h3><div>The chemical analysis of nanoparticles of the study revealed that cerium oxide nanoparticles exhibited better and more regular morphological characteristics compared to nanoparticles coated with PEG and PVP polymers in terms of size. In addition, cerium oxide nanoparticles combined with PVP polymer did not retain the morphology at the nano level. Toxicological studies demonstrated a reduction in the toxicity of cerium oxide nanoparticles when coated with PEG and PVP polymers.</div></div><div><h3>Discussion and conclusion</h3><div>The study found that PEG coating significantly reduces the cytotoxicity of cerium oxide nanoparticles more effectively than PVP coating by mitigating oxidative stress. This approach presents a promising strategy for developing safer cerium oxide-based products for pharmaceutical and medical applications.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"105 ","pages":"Article 106022"},"PeriodicalIF":2.6,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477262","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