{"title":"Transcription Factor yin-Yang 1 augments nucleoporin 93 oncogene activity and modulates bladder Cancer malignancy","authors":"Gang Zhang , Wei Wei , Shao Li , Jinyi Yang","doi":"10.1016/j.tiv.2024.105875","DOIUrl":"10.1016/j.tiv.2024.105875","url":null,"abstract":"<div><h3>Objective</h3><p>This study aims to investigate the functional interplay between transcription factor YY1 and nucleoporin 93 (NUP93) in regulating the malignancy of bladder cancer cells.</p></div><div><h3>Methods</h3><p>NUP93 expressions in bladder cancer tissues and normal counterparts were analyzed using a public dataset and clinical samples. NUP93 and Yin Yang 1 (YY1) mRNA expression and protein levels in T24 and RT4 cells were determined by Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. The effect of NUP93 knockdown on the proliferation, migration, and invasion capabilities of cells was evaluated. Concurrently, transcriptional regulation of NUP93 by YY1 was confirmed using a dual luciferase assay. The effect of NUP93 knockdown on tumorigenesis was evaluate in a subcutaneous xenograft mouse model.</p></div><div><h3>Results</h3><p>Elevated levels of NUP93 in bladder cancer tissues and cell lines were observed. Silencing NUP93 significantly suppressed glycolysis, impeded the growth, migration, invasion and tumor formation of bladder cancer cells. The transcription factor YY1 acted as a positive regulator to upregulate NUP93 expression. YY1 overexpression partially rescued the effects of NUP93 silencing on bladder cancer cells.</p></div><div><h3>Conclusion</h3><p>Our results uncovered transcription factor YY1 as a positive regulator of NUP93 expression, and NUP93 serves as an oncogenic factor to sustain the malignancy of bladder cancer cells. These findings suggest that targeting the YY1-NUP93 axis could offer novel therapeutic strategies for bladder cancer treatment.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105875"},"PeriodicalIF":3.2,"publicationDate":"2024-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141302094","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}
Thiago S. Santos , Marcelo O. Bahia , Adriana C. Guimarães , Carolina R.T. Souza , Nilton A. Muto , Hervé Rogez , Rommel M.R. Burbano
{"title":"In vitro assessment of the genotoxic and cytotoxic effects of clarified açai (Euterpe oleracea MART) extract in a gastric cancer cell line (AGP01 cells).","authors":"Thiago S. Santos , Marcelo O. Bahia , Adriana C. Guimarães , Carolina R.T. Souza , Nilton A. Muto , Hervé Rogez , Rommel M.R. Burbano","doi":"10.1016/j.tiv.2024.105873","DOIUrl":"10.1016/j.tiv.2024.105873","url":null,"abstract":"<div><p><em>Açaí</em> (<em>Euterpe oleracea</em> MART) is a fruit of great importance for the Amazon region in nutritional, cultural and socioeconomic terms. In recent years, <em>açaí</em> has <!--> <!-->been the subject of several studies due to its beneficial properties for health, including effects against tumor cells. Therefore, the present work aimed to evaluate <em>in vitro</em> the genotoxic and cytotoxic effects of the clarified extract of <em>açaí</em> juice in a human metastatic gastric cancer cell line (AGP01 cells). For comparison purposes, a non-transformed cell line of African green monkey renal epithelial cells (VERO cells) was used. The viability assay by resazurin reduction, the comet assay, the determination of cell death by differential fluorescent dyes and the wound healing migration assay were performed. A reduction in viability was observed only in the AGP01 line within 72 h. There was no genotoxic damage or cell death (through apoptosis or necrosis) in any of the cell lines. However, <em>açaí</em> extract induced motility reduction in both cell lines. The reduction in cell viability and the induction of the anti-migratory effect in the AGP01 cell line opens perspectives for exploring the potential of <em>açaí</em> as an adjuvant in the treatment of gastric cancer.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105873"},"PeriodicalIF":3.2,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293963","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}
{"title":"(-)-Epigallocatechin gallate as an inhibitor of hemoglobin-catalyzed lipid oxidation: molecular mechanism of action and nutritional application","authors":"Jia-Xin Li, Naihao Lu, Rong Tian","doi":"10.1016/j.tiv.2024.105871","DOIUrl":"10.1016/j.tiv.2024.105871","url":null,"abstract":"<div><p>Hemoglobin (Hb) is effective inducer for lipid oxidation and protein–polyphenol interaction is a well-known phenomenon. The effects of the interaction of (-)-epigallocatechin gallate (EGCG) with Hb on lipid oxidation were rarely elucidated. The detailed interaction between bovine Hb and EGCG was systematically explored by experimental and theoretical approaches, to illustrate the molecular mechanisms by which EGCG influenced the redox states and stability of Hb. EGCG would bind to the central pocket of protein with one binding site to form Hb-EGCG complex. The binding constant for Hb-EGCG complex was 0.34 × 10<sup>4</sup> M<sup>−1</sup> at 277 K, and thermodynamic parameters (ΔH > 0, ΔS > 0 and ΔG < 0) revealed the participation of hydrophobic forces in the binding process. The binding of EGCG would increase the compactness of protein molecule and diminish the crevice near the heme cavity, which was responsible for the reduction of met-Hb to oxy-Hb and inhibition of hemin release from met-Hb. Moreover, EGCG efficiently suppressed Hb-caused lipid oxidation in liposomes and cod muscles, which was possibly attributed to the reduction to oxy-Hb state and declined hemin dissociation from met-Hb. Altogether, our results provide significant insights into the binding of EGCG to redox-active Hb, which represents a novel mechanism for the anti-oxidant capacity of EGCG in human health and is favorable to the applications of natural EGCG in the good quality of Hb-containing products.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105871"},"PeriodicalIF":3.2,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293960","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}
Solange Soares , Jayne Torres de Sousa , Fernanda Brião Menezes Boaretto , Juliana Bondan da Silva , Duani Maria dos Santos , Ana Letícia Hilario Garcia , Juliana da Silva , Ivana Grivicich , Jaqueline Nascimento Picada
{"title":"Amantadine mitigates the cytotoxic and genotoxic effects of doxorubicin in SH-SY5Y cells and reduces its mutagenicity","authors":"Solange Soares , Jayne Torres de Sousa , Fernanda Brião Menezes Boaretto , Juliana Bondan da Silva , Duani Maria dos Santos , Ana Letícia Hilario Garcia , Juliana da Silva , Ivana Grivicich , Jaqueline Nascimento Picada","doi":"10.1016/j.tiv.2024.105874","DOIUrl":"10.1016/j.tiv.2024.105874","url":null,"abstract":"<div><p>Amantadine (AMA) is a useful drug in neuronal disorders, but few studies have been performed to access its toxicological profile. Conversely, doxorubicin (Dox) is a well-known antineoplastic drug that has shown neurotoxic effects leading to cognitive impairment. The aims of this study are to evaluate the cytotoxic, genotoxic, and mutagenic effects of AMA, as well as its possible protective actions against deleterious effects of Dox. The Salmonella/microsome assay was performed to assess mutagenicity while cytotoxicity and genotoxicity were evaluated in SH-SY5Y cells using MTT and comet assays. Possible modulating effects of AMA on the cytotoxicity, genotoxicity, and mutagenicity induced by Dox were evaluated through cotreatment procedures. Amantadine did not induce mutations in the Salmonella/microsome assay and decreased Dox-induced mutagenicity in the TA98 strain. AMA reduced cell viability and induced DNA damage in SH-SY5Y cells. In cotreatment with Dox, AMA attenuated the cytotoxicity of Dox and showed an antigenotoxic effect. In conclusion, AMA does not induce gene mutations, although it has shown a genotoxic effect. Furthermore, AMA decreases frameshift mutations induced by Dox as well as the cytotoxic and genotoxic effects of Dox in SH-SY5Y cells, suggesting that AMA can interfere with Dox mutagenic activity and attenuate its neurotoxic effects.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105874"},"PeriodicalIF":3.2,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293961","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}
{"title":"Effects of polystyrene nanoplastic size on zebrafish embryo development","authors":"Varissara Chantho , Siwapech Sillapaprayoon , Rattaporn Saenmuangchin , Jasmine Pongkasem , Kulwadee Theanngern , Fahriye Ceyda Dudak Şeker , Sasitorn Aueviriyavit , Wittaya Pimtong","doi":"10.1016/j.tiv.2024.105868","DOIUrl":"10.1016/j.tiv.2024.105868","url":null,"abstract":"<div><p>Polystyrene nanoplastics (PS) require a comprehensive evaluation of their toxicity and potential risks to humans and the environment. The zebrafish model, a well-established animal model increasingly utilized for nanotoxicity assessments, was employed in this study. Our research aimed to explore the toxic effects of PS with sizes of 30, 100, 200, and 450 nm on zebrafish embryos. Exposure experiments were conducted on embryos at 4 h post-fertilization (hpf) using various concentrations of nanoparticles (20, 40, 60, 80, and 100 mg/L) until 96 hpf. Notably, PS ranging from 100 to 450 nm did not adversely affect zebrafish embryo development. However, PS with a size of 30 nm at a concentration of 100 mg/L resulted in embryo mortality but not embryonic malformations. Furthermore, our investigation confirmed the uptake of these nanoparticles by zebrafish larvae following the opening of their mouths, with the particles being found predominantly in the digestive system of the larvae. Additionally, 30 nm PS were found to significantly modulate the expression levels of genes associated with oxidative stress and apoptosis. These findings highlight the developmental impacts of 30 nm PS on zebrafish embryos, raising concerns about potential similar consequences in humans. Considering our findings, it is essential to encourage further research into the management and regulation of PS to mitigate their potential environmental and health impacts.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105868"},"PeriodicalIF":3.2,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141293962","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}
Wei-Bin Hu , Yi-Ting Liu , Jing Li , Ying Wang , Xuan-Zi Sun , Ming-Yu Hua , Xue-Ting Liu , Bei-Na Hui
{"title":"Pristimerin exhibits anti-cancer activity by inducing ER stress and AKT/GSK3β pathway through increasing intracellular ROS production in human esophageal cancer cells","authors":"Wei-Bin Hu , Yi-Ting Liu , Jing Li , Ying Wang , Xuan-Zi Sun , Ming-Yu Hua , Xue-Ting Liu , Bei-Na Hui","doi":"10.1016/j.tiv.2024.105867","DOIUrl":"10.1016/j.tiv.2024.105867","url":null,"abstract":"<div><p>Pristimerin (Pris), a bioactive triterpenoid compound extracted from the <em>Celastraceae</em> and <em>Hippocrateaceae</em> families, has been reported to exhibit an anti-cancer property on various cancers. However, the effects of Pris on esophageal cancer are poorly investigated. This current study sought to explore the activity and underlying mechanism of Pris against human esophageal squamous cell carcinoma (ESCC) cells. We demonstrated that Pris showed cytotoxicity in TE-1 and TE-10 ESCC cell lines, and significantly inhibited cell viability in a concentration dependent manner. Pris induced G0/G1 phase arrest and triggered apoptosis. It was also observed that the intracellular ROS level was remarkedly increased by Pris treatment. Besides, the function of Pris mediating the activation of ER stress and the inhibition of AKT/GSK3β signaling pathway in TE-1 and TE-10 cells was further confirmed, which resulted in cell growth inhibition. And moreover, we revealed that all of the above pathways were regulated through ROS generation. In conclusion, our findings suggested that Pris might be considered as a novel natural compound for the developing anti-cancer drug candidate for human esophageal cancer.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105867"},"PeriodicalIF":3.2,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288943","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}
Jinru Zhao , Jian Gao , Sijia Ma, Xintong Chen, Jun Wang
{"title":"Predicting the potential risks posed by antidepressants as emerging contaminants in fish based on network pharmacological analysis","authors":"Jinru Zhao , Jian Gao , Sijia Ma, Xintong Chen, Jun Wang","doi":"10.1016/j.tiv.2024.105872","DOIUrl":"https://doi.org/10.1016/j.tiv.2024.105872","url":null,"abstract":"<div><p>This study conducted a network pharmacology-based analysis to simultaneously discern a broad spectrum of potential environmental risks and health effects of antidepressants, a common class of pharmaceutical emerging contaminants (PECs) possessing a complex pharmacological profile, and <em>in silico</em> predict the adverse phenotypes potentially occurring in fish associated with exposure to antidepressants and their mixtures under realistic exposure scenarios. Results showed that 24 of the included 39 antidepressants had been detected worldwide in water environment across 50 countries. Using the environmentally realistic exposure scenario for China as an example, the predicted blood concentrations of antidepressant residues that were generated based on the Fish Plasma Model ranged from 37.89 (Alprazolam) to 16,772.05 (Sertraline) ng/L in exposed fish. Hazard-based bioactivity network without regard to concentration data was composed of 148 potential targets and 701 antidepressant-target interactions. After filtering each antidepressant-target interaction node using the predicted drug concentrations in the blood of fish under realistic exposure scenarios in China, an environmental risk-based network was refined and showed that 11 targets, including muscarinic acetylcholine receptor M1, alpha-2B adrenergic receptor, serotonin 2 A receptor, <em>etc.</em> might be modulated by antidepressants at concentrations equal to or below the environmental exposure levels and their mixtures in fish. Environmentally relevant concentrations of antidepressants in water samples from China might perturb the behavior, stress response, phototaxis, and development in exposed fish.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105872"},"PeriodicalIF":3.2,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141291058","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}
Pincha Devage Sameera Madushan Fernando , Mei Jing Piao , Herath Mudiyanselage Udari Lakmini Herath , Kyoung Ah Kang , Chang Lim Hyun , Eui Tae Kim , Young Sang Koh , Jin Won Hyun
{"title":"Hyperoside reduced particulate matter 2.5-induced endoplasmic reticulum stress and senescence in skin cells","authors":"Pincha Devage Sameera Madushan Fernando , Mei Jing Piao , Herath Mudiyanselage Udari Lakmini Herath , Kyoung Ah Kang , Chang Lim Hyun , Eui Tae Kim , Young Sang Koh , Jin Won Hyun","doi":"10.1016/j.tiv.2024.105870","DOIUrl":"10.1016/j.tiv.2024.105870","url":null,"abstract":"<div><p>Particulate matter 2.5 (PM<sub>2.5</sub>) causes skin aging, inflammation, and impaired skin homeostasis. Hyperoside, a flavanol glycoside, has been proposed to reduce the risk of diseases caused by oxidative stress. This study evaluated the cytoprotective potential of hyperoside against PM<sub>2.5</sub>-induced skin cell damage. Cultured human HaCaT keratinocytes were pretreated with hyperoside and treated with PM<sub>2.5</sub>. Initially, the cytoprotective and antioxidant ability of hyperoside against PM<sub>2.5</sub> was evaluated. Western blotting was further employed to investigate endoplasmic reticulum (ER) stress and cellular senescence and for evaluation of cell cycle regulation-related proteins. Hyperoside inhibited PM<sub>2.5</sub>-mediated ER stress as well as mitochondrial damage. Colony formation assessment confirmed that PM<sub>2.5</sub>-impaired cell proliferation was restored by hyperoside. Moreover, hyperoside reduced the activation of PM<sub>2.5</sub>-induced ER stress-related proteins, such as protein kinase R-like ER kinase, cleaved activating transcription factor 6, and inositol-requiring enzyme 1. Hyperoside promoted cell cycle progression in the G<sub>0</sub>/G<sub>1</sub> phase by upregulating the PM<sub>2.5</sub>-impaired cell cycle regulatory proteins. Hyperoside significantly reduced the expression of PM<sub>2.5</sub>-induced senescence-associated β-galactosidase and matrix metalloproteinases (MMPs), such as MMP-1 and MMP-9. Overall, hyperoside ameliorated PM<sub>2.5</sub>-impaired cell proliferation, ER stress, and cellular senescence, offering potential therapeutic implications for mitigating the adverse effects of environmental pollutants on skin health.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105870"},"PeriodicalIF":3.2,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0887233324001000/pdfft?md5=62650fe810a7b69b52f5bd76fe6fe769&pid=1-s2.0-S0887233324001000-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288942","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}
{"title":"Assessment of silver nanoparticles' antitumor effects: Insights into cell number, viability, and morphology of glioblastoma and prostate cancer cells","authors":"Isabel Cristina Gomes Santos, Michelle Lopes de Oliveira, Renata Carvalho Silva, Celso Sant'Anna","doi":"10.1016/j.tiv.2024.105869","DOIUrl":"10.1016/j.tiv.2024.105869","url":null,"abstract":"<div><p>Silver nanoparticles (AgNPs) hold promise for cancer therapy. This study aimed to evaluate their impact on tumor and non-tumor cell number, viability, and morphology. Antitumor activity was tested on U-87MG (glioblastoma) and DU-145 (prostate cancer) cell lines. Treatment with AgNPs notably reached a reduction of U-87MG and DU-145 cell growth by 89.30% and 79.74%, respectively, resulting in slower growth rates. AgNPs induced DNA damage, evidenced by reduced nuclear area and DNA content via fluorescent image-based analyses. Conversely, HFF-1 non-tumor cells displayed no significant changes post-AgNPs exposure. Viability assays revealed substantial reductions in U-87MG and DU-145 cells (79% and 63% in MTT assays, 30% and 52.2% in high-content analyses), while HFF-1 cells exhibited lower sensitivity. Tumor cells had notably lower IC<sub>50</sub> values than non-tumor cells, indicating selective susceptibility. Transmission electron microscopy (TEM) showed morphological changes post-AgNPs administration, including increased vacuoles, myelin figures, membrane ghosts, cellular extravasation, and membrane projections. The findings suggest the potential of AgNPs against glioblastoma and prostate cancer, necessitating further exploration across other cancer cell lines.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105869"},"PeriodicalIF":3.2,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141288941","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}
{"title":"Bisphenol a accelerates the glucolipotoxicity-induced dysfunction of rat insulinoma cell lines: An implication for a potential risk of environmental bisphenol a exposure for individuals susceptible to type 2 diabetes","authors":"Chengmeng Huang, Xiaolin Chen, Zedong Ouyang, Lingxue Meng, Jian Liu, Qihua Pang, Ruifang Fan","doi":"10.1016/j.tiv.2024.105866","DOIUrl":"10.1016/j.tiv.2024.105866","url":null,"abstract":"<div><p>Epidemiological studies have suggested a correlation between bisphenol A (BPA) and type 2 diabetes (T2DM). The effects of BPA on β-cell dysfunction may reveal the risks from an in vitro perspective. We used the rat insulinoma (INS-1) cell lines (a type of β-cells) to set up normal or damaged models (DM), which were exposed to various concentrations of BPA (0.001, 0.01, 0.1, 1, 10 and 100 μM). An increase in reactive oxygen species (ROS) and apoptosis, and a decrease in cell viability were observed in INS-1 cells exposed to high doses of BPA for 48 h. Interestingly, exposure to lower doses of BPA for 24 h resulted in increased ROS levels and apoptosis rates in INS-1 in the DM group, along with decreased cell viability, suggesting that BPA exerts toxicity to INS-1 cells, particularly to the DM group. Insulin levels and Glut2 expression, glucose consumption, intracellular Ca<sup>2+</sup> and insulin secretion were increased in INS-1 cells after 48 h exposure to high dose of BPA. Stronger effects were observed in the DM group, even those exposed to low doses of BPA for 24 h. Moreover, BPA inhibited high glucose-stimulated insulin secretion in these cells. Our research suggests that low doses of BPA exacerbate the dysfunction caused by glucolipotoxicity, implying environmental BPA exposure poses a risk for individuals with prediabetes or T2DM.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"99 ","pages":"Article 105866"},"PeriodicalIF":3.2,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141285410","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}