Toxicology in Vitro最新文献

{"title":"Involvement of Sirt1-FoxO3a-Bnip3 axis and autophagy mediated mitochondrial turnover in according protection to hyperglycemic NRK-52E cells by Berberine","authors":"Sugandh Saxena ,&nbsp;Sumit Kumar Anand ,&nbsp;Ankita Sharma ,&nbsp;Poonam Kakkar","doi":"10.1016/j.tiv.2024.105916","DOIUrl":"10.1016/j.tiv.2024.105916","url":null,"abstract":"<div><p>Aberrant accumulation of dysfunctional mitochondria in renal cells during hyperglycemia signifies perturbed autophagy and mitochondrial turnover. This study aims to focus on the underlying mechanism involved in autophagy and mitophagy inducing efficacy of Berberine (isoquinoline alkaloid) in hyperglycemic NRK-52E cells. Berberine mediated protection to hyperglycemic cells prevented alteration in mitochondrial structure and function. Treatment with SRT-1720 (Sirt1 activator) enhanced autophagy, decreased apoptosis, upregulated expression of downstream moieties (FoxO3a and Bnip3) and ameliorated mitochondria related anomalies while nicotinamide (Sirt1 inhibitor) treatment exhibited reversal of the same. GFP reporter assay ascertained enhanced transcriptional activity of FoxO in Berberine-treated hyperglycemic cells, which was found to be correlated to increased expression of downstream protein Bnip3. Knocking down FoxO3a disrupted autophagy and stimulated apoptosis. <em>N</em>-acetyl-L-cysteine pre-treatment confirmed that generation of ROS intervened high glucose induced toxicity in NRK-52E cells. Berberine co-treatment resulted in differential expressions of key proteins involved in autophagy and mitophagy like LC3B, ATGs, Beclin1, Sirt1, Bnip3, FoxO3a and Parkin. Further, enhanced mitophagy in Berberine-treated cells was confirmed by transmission electron microscopy. Thus, our findings give evidence that the protection accorded by Berberine against hyperglycemia in renal proximal tubular cells (NRK-52E) involves instigation of Sirt1-FoxO3a-Bnip3 axis and autophagy mediated mitophagy induction.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"100 ","pages":"Article 105916"},"PeriodicalIF":2.6,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914579","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":"In vitro impacts of polystyrene microplastics and environmental pollutants on ethoxyresorufin-O-deethylase and glutathione S-transferase activity in Mossambica tilapia","authors":"Yan Yin ,&nbsp;Haiyan Wang ,&nbsp;Guijing Ouyang ,&nbsp;Daxiong Han","doi":"10.1016/j.tiv.2024.105915","DOIUrl":"10.1016/j.tiv.2024.105915","url":null,"abstract":"<div><p>Microplastic (MP) pollution is a potential threat to marine organisms. <em>In vitro</em> toxicity of MPs and other pollutants, such as pharmaceutically active compounds (PhACs) and brominated flame retardants (BFRs), has been understudied. This study aimed to investigate the effects of polystyrene microplastics (PS-MPs) with different particle sizes on two biomarkers: ethoxyresorufin-O-deethylase (EROD) and glutathione S-transferase (GST) in tilapia liver homogenates. The study also examined the combined effects of PS-MPs with various environmental contaminants, including three metal ions (Cu²⁺, Zn²⁺, Pb²⁺), three BFRs, and six PhACs. PS-MPs alone had no remarkable effects on the two biomarkers at the selected concentrations. However, PS-MPs combined with other pollutants significantly affected the two biomarkers in most situations. For EROD activity, PS + metal ions (except Zn²⁺ at 1000 μg/L), PS + BFRs (except decabromodiphenyl oxide (BDE-209)) or PS+ trimethoprim (TMP) significantly inhibited activity values, whereas PS+ 4-acetaminophen (AMP) induced EROD activity. For GST, PS together with most tested pollutants (except PS+ ibuprofen (IBF)) greatly decreased the activities. Accordingly, future research should focus on combined toxicity of mixtures to set more reasonable environmental safety evaluation standards.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"100 ","pages":"Article 105915"},"PeriodicalIF":2.6,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903606","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":"Estrogen receptor/androgen receptor transcriptional activation of benzophenone derivatives and integrated approaches to testing and assessment (IATA) for estrogenic effects","authors":"Handule Lee,&nbsp;Juyoung Park,&nbsp;Darlene M. Ortiz,&nbsp;Kwangsik Park","doi":"10.1016/j.tiv.2024.105914","DOIUrl":"10.1016/j.tiv.2024.105914","url":null,"abstract":"<div><p>Estrogen receptor (ER) and androgen receptor (AR) transactivation assays for the benzophenone compounds (BPs) were performed using hERα-HeLa-9903 cells for ER and MMTV/22Rv1_GR-KO cells for AR. Results showed that some BPs, such as BP-1, BP-2, 4OH-BP, 4DHB, and 4-MBP, showed agonistic activity on ER with a higher RPCmax than 1 nM 17-β estradiol. The other BPs (BP, BP-3, BP-6, BP-7, and BP-8) showed low RPCmax in accordance with the OECD Test guideline (TG) 455 criteria, with BP-4 as the only ER-negative. However, the potency of the BPs was at least 1000 times less than the reference chemical, 17-β-estradiol. None of the BPs exhibited agonistic activity on AR except BP-2 which showed a small increase in activity. For further evaluation of the estrogenic effect of BPs based on the integrated approaches to testing and assessment (IATA) approach, existing data on ER binding, steroidogenesis, MCF-7 cell proliferation, and <em>in vivo</em> uterotrophic assays were collected and evaluated. There seemed to be a close association between the <em>in vitro</em> data on BPs, especially ER transcriptional activity, and the <em>in vivo</em> results of increased uterine weight. This case study implied that integrated approaches using <em>in vitro</em> data can be a useful tool for the prediction of <em>in vivo</em> data for estrogenic effects, without the need for additional animal toxicity tests.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"100 ","pages":"Article 105914"},"PeriodicalIF":2.6,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879811","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":"Streptococcus mitis enhances metal-induced apoptosis in reconstructed human gingiva but not skin","authors":"Yan Zhang ,&nbsp;Lin Shang ,&nbsp;Sanne Roffel ,&nbsp;Sander W. Spiekstra ,&nbsp;Dongmei Deng ,&nbsp;Susan Gibbs","doi":"10.1016/j.tiv.2024.105913","DOIUrl":"10.1016/j.tiv.2024.105913","url":null,"abstract":"<div><h3>Background</h3><p>Commensal bacteria colonizing oral mucosa and skin play an essential role in maintaining host-microbiome homeostasis. It is unknown whether cytotoxicity resulting from metal ions leaching from medical devices may be influenced by commensal microbes.</p></div><div><h3>Objective</h3><p>Determine whether the extent of apoptosis triggered by nickel or titanium ions is influenced by <em>Streptococcus mitis</em> and whether apoptosis occurs via the intrinsic or extrinsic apoptosis pathway.</p></div><div><h3>Methods</h3><p>Reconstructed Human Gingiva (RHG) and Skin (RHS) were topically exposed to titanium or nickel salts in the presence or absence of <em>S. mitis</em>. Cytotoxicity and apoptosis were assessed by histology, immunohistochemistry, TUNEL assay, and Western Blot.</p></div><div><h3>Results</h3><p><em>S. mitis</em> alone resulted in negligible cytotoxicity. After metal exposure, localized apoptosis was observed in the epithelium and fibroblasts within the lamina propria hydrogel of both RHG and RHS. <em>S. mitis</em> enhanced metal-mediated apoptosis in gingiva but not in skin. Apoptosis was mediated via the extrinsic pathway caspase 8. Activation of the execution phase of apoptosis occurred via caspases 3 and 7, and PARP-1.</p></div><div><h3>Conclusion</h3><p>Our study supports the finding that metals have irritant, cytotoxic properties resulting in apoptosis when leaching into skin or gingiva. Particularly for gingiva, commensal microbes exaggerate this detrimental effect.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"100 ","pages":"Article 105913"},"PeriodicalIF":2.6,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0887233324001437/pdfft?md5=314e5920e7587de8fb8dc5dbe28b2537&pid=1-s2.0-S0887233324001437-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141839044","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":"Study on percutaneous penetration of representative cosmetic ingredients in a baby wipe product in an in vitro diaper rash skin model","authors":"Ning Li ,&nbsp;Peter Styczynski ,&nbsp;Roger Gibb ,&nbsp;Chuiying Li ,&nbsp;Randy Marsh","doi":"10.1016/j.tiv.2024.105912","DOIUrl":"10.1016/j.tiv.2024.105912","url":null,"abstract":"<div><p>Studying percutaneous penetration of various cosmetic ingredients through intact and compromised skin can provide insight on quantitative exposure assessment for baby products intended for diapered skin. We developed an <em>in vitro</em> model (tape-stripped human skin) designed to achieve the Trans-Epidermal Water Loss values measured in babies with various degrees of diaper dermatitis. Six reference compounds showed the impact of physicochemical properties on absorption through this “diaper rash” skin model. Under simulated diaper conditions, dermal absorption of cosmetic ingredients (phenoxyethanol, sodium benzoate, benzyl alcohol, disodium EDTA, and propylene glycol) was different, but &lt;100%. Additionally, the effect of diaper rash on dermal absorption of well-absorbed ingredients (phenoxyethanol, sodium benzoate, and benzyl alcohol) was limited (enhancement of 1.1–1.3), while the enhancement for moderately absorbed compounds (disodium EDTA and propylene glycol) was 1.8–3.3. Absorption <em>via</em> skin with “diaper rash” is specific to individual ingredients and exposure conditions, so a fixed uncertainty factor is not appropriate for safety assessment. The data support that the default 100% dermal absorption commonly used in first-tier risk assessments for diapered skin is conservative. This diaper rash skin model provides a practical tool of estimating absorption of various ingredients in baby products intended for diapered skin.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"100 ","pages":"Article 105912"},"PeriodicalIF":2.6,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0887233324001425/pdfft?md5=dbb80735eed805d359f9e88ce98d8c15&pid=1-s2.0-S0887233324001425-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789811","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":"Investigating the mechanisms of action of thyroid disruptors: A multimodal approach that integrates in vitro and metabolomic analysis","authors":"Naïs Clavel Rolland ,&nbsp;Fanny Graslin ,&nbsp;Frédéric Schorsch ,&nbsp;Thierry Pourcher ,&nbsp;Olivier Blanck","doi":"10.1016/j.tiv.2024.105911","DOIUrl":"10.1016/j.tiv.2024.105911","url":null,"abstract":"<div><p>The thyroid gland, a vital component of the endocrine system, plays a pivotal role in regulating metabolic processes, growth, and development. To better characterize thyroid system disrupting chemicals (TSDC), we followed the next-generation risk assessment approach, which further considers the mechanistic profile of xenobiotics. We combined targeted <em>in vitro</em> testing with untargeted metabolomics. Four known TSDC, propyl-thiouracil (PTU), sodium perchlorate, triclosan, and 5-pregnen-3β-ol-20-one-16α‑carbonitrile (PCN) were investigated using rat <em>in vitro</em> models, including primary hepatocytes, PCCL3 cells, thyroid microsomes, and three-dimensional thyroid follicles. We confirmed each compound's mode of action, PTU inhibited thyroperoxidase activity and thyroid hormones secretion in thyroid cells model, sodium perchlorate induced a NIS-mediated iodide uptake decrease as triclosan to a lesser extent, and PCN activated expression and activity of hepatic enzymes (CYPs and UGTs) involved in thyroid hormones metabolism. In parallel, we characterized intracellular metabolites of interest. We identified disrupted basal metabolic pathways, but also metabolites directly linked to the compound's mode of action as tyrosine derivates for sodium perchlorate and triclosan, bile acids involved in beta-oxidation, and precursors of cytochrome P450 synthesis for PCN. This pilot study has provided metabolomic fingerprinting of dedicated TSDC exposures, which could be used to screen and differentiate specific modes of action.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"100 ","pages":"Article 105911"},"PeriodicalIF":2.6,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141789810","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":"Pro-inflammatory and genotoxic responses by metal oxide nanomaterials in alveolar epithelial cells and macrophages in submerged condition and air-liquid interface: An in vitro-in vivo correlation study","authors":"Emilio Di Ianni ,&nbsp;Johanna Samulin Erdem ,&nbsp;Shan Narui ,&nbsp;Håkan Wallin ,&nbsp;Iseult Lynch ,&nbsp;Ulla Vogel ,&nbsp;Nicklas Raun Jacobsen ,&nbsp;Peter Møller","doi":"10.1016/j.tiv.2024.105897","DOIUrl":"10.1016/j.tiv.2024.105897","url":null,"abstract":"<div><p>Studies on in vitro-in vivo correlations of inflammatory and genotoxic responses are needed to advance new approach methodologies. Here, we assessed pro-inflammatory and genotoxic responses by 13 nanosized metal oxides (nMeOx) and quartz (DQ12) in alveolar epithelial cells (A549) and macrophages (THP-1a) exposed in submerged conditions, and in A549:THP-1a co-cultures in air-liquid interface (ALI) system. Soluble nMeOx produced the highest <em>IL-8</em> expression in A549 and THP-1a cells in submerged conditions (≥2-fold, <em>p</em> &lt; 0.05), whereas only CuO caused a strong response in co-cultures exposed in the ALI system (13-fold, p &lt; 0.05). <em>IL-8</em> expression in A549 cells with concentrations as nMeOx specific surface area (SSA) correlated with neutrophil influx in mice (<em>r</em> = 0.89–0.98, <em>p</em> &lt; 0.05). Similarly, <em>IL-8</em> expression in THP-1a cell with concentrations as mass and SSA (when excluding soluble nMeOx) correlated with neutrophil influx in mice (<em>r</em> = 0.81–0.84, <em>p</em> &lt; 0.05). DNA strand breaks (SB) was measured by the comet assay. We used a scoring system that categorizes effects in standard deviation units for comparison of genotoxicity in different models. Concordant genotoxicity was observed between SB levels in vitro (A549 and co-culture) and in vivo (broncho-alveolar lavage fluid cells and lung tissue). In conclusion, this study shows in vitro-in vivo correlations of nMeOx-induced inflammatory and genotoxic responses.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"100 ","pages":"Article 105897"},"PeriodicalIF":2.6,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0887233324001279/pdfft?md5=5b724667be086bc68d2dcfd12998b715&pid=1-s2.0-S0887233324001279-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141725108","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":"Knowledge infrastructure for integrated data management and analysis supporting new approach methods in predictive toxicology and risk assessment","authors":"Barry Hardy ,&nbsp;Tomaz Mohoric ,&nbsp;Thomas Exner ,&nbsp;Joh Dokler ,&nbsp;Maja Brajnik ,&nbsp;Daniel Bachler ,&nbsp;Ody Mbegbu ,&nbsp;Nora Kleisli ,&nbsp;Lucian Farcal ,&nbsp;Krzysztof Maciejczuk ,&nbsp;Haris Rašidagić ,&nbsp;Ghada Tagorti ,&nbsp;Pascal Ankli ,&nbsp;Daniel Burgwinkel ,&nbsp;Divanshu Anand ,&nbsp;Ugis Sarkans ,&nbsp;Awais Athar","doi":"10.1016/j.tiv.2024.105903","DOIUrl":"10.1016/j.tiv.2024.105903","url":null,"abstract":"<div><p>The EU-ToxRisk project (2016–2021) was a large European project working towards shifting toxicological testing away from animal tests, towards a toxicological assessment based on comprehensive mechanistic understanding of cause-consequence relationships of chemical adverse effects. More than 40 partners from scientific institutions, industry and regulators coordinated their work towards this goal in a six-year long programme. The breadth and variety of data and knowledge generated, presented a challenging data management landscape.</p><p>Here, we describe our approach to data management as developed under EU-ToxRisk. The main building blocks of the data infrastructure are: 1) An easy-to-use, extensible data and metadata format; 2) A flexible system with protocols for data capture and sharing from the entire consortium; 3) A methods database for describing and reviewing data generation and processing protocols; 4) Data archiving using a sustainable resource; 5) Data transformation from the archive to the system that provides granular access; 6) Application Programming Interface (API) for access to individual data points; 7) Data exploration and analysis modules, based on a «web notebook» approach to executable data processing documentation; and 8) Knowledge portal that ties together all of the above and provides a collaboration space for information exchange across the consortium. This knowledge infrastructure is being extended and refined for the support of follow-up projects (RISK-HUNT3R, ASPIS cluster, European Open Science Cloud (2021–2026)).</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"100 ","pages":"Article 105903"},"PeriodicalIF":2.6,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0887233324001334/pdfft?md5=8606aa6155e93a4fd5d6ae8c120eed72&pid=1-s2.0-S0887233324001334-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762608","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":"In vitro cytotoxicity of six per- and polyfluoroalkyl substances (PFAS) in human immune cell lines","authors":"Jennifer R. McCall ,&nbsp;Kathryn T. Sausman ,&nbsp;Ariel P. Brown ,&nbsp;Ralph N. Mead","doi":"10.1016/j.tiv.2024.105910","DOIUrl":"10.1016/j.tiv.2024.105910","url":null,"abstract":"<div><p><em>Per</em>- and Polyfluoroalkyl substances (PFAS) are a group of persistent long-lived chemicals with global environmental contamination. The published literature is rife with confusing and sometimes contradictory effects of PFAS on animal and cell models, as well as epidemiological studies. Cytotoxicity studies are often used as an early indicator to guide safety requirements, regulation, and further studies and thus can be useful to understand important toxicity differences by various PFAS. Recent studies have found that PFAS are not equivalently toxic on all cell types, and that not all cell types exhibit the same sensitivity to individual PFAS. However, immune cells have not been well studied. As immune cells are important for regulating responses to environmental toxins, infection, and cancer, we sought to discover the sensitivity of these cells to various PFAS, including legacy and replacement compounds. We assessed a range of concentrations and found that immune cells are generally more robust when exposed to PFAS, and that Jurkat T-cells were more sensitive than THP-1 monocytes. As monocytes are critical for coordinating inflammatory responses to external threats with cell death cascades, we further investigated these cells. We discovered that THP-1 cells do not undergo organized or programmed death, such as apoptosis or pyroptosis, and instead PFAS exposure results in a more necrotic/lytic and unorganized death, likely contributing to potential inflammatory effects downstream.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"100 ","pages":"Article 105910"},"PeriodicalIF":2.6,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141762695","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":"Nrf2 affects DNA damage repair and cell apoptosis through regulating HR and the intrinsic Caspase-dependent apoptosis pathway in TK6 cells exposed to hydroquinone","authors":"Lin Chen ,&nbsp;Pu Guo ,&nbsp;Lu Zhai,&nbsp;Lingxue Yu,&nbsp;Delong Zhu,&nbsp;Xiaoyi Hu,&nbsp;Zhuanzhuan Li,&nbsp;Yuting Chen,&nbsp;Qian Sun,&nbsp;Lei Sun,&nbsp;Hao Luo,&nbsp;Huanwen Tang","doi":"10.1016/j.tiv.2024.105901","DOIUrl":"10.1016/j.tiv.2024.105901","url":null,"abstract":"<div><p>Hydroquinone (HQ) is one of benzene metabolites that can cause oxidative stress damage and Homologous recombination repair (HR). A good deal of reactive oxygen species (ROS) generated by oxidative stress can trigger apoptotic signaling pathways. The nuclear factor erythroid 2-related factor 2 (Nrf2) can regulate the cell response to oxidative stress damage. The aim of this study was to explore whether Nrf2 participate in HQ-induced apoptosis and its mechanism. The findings displayed that HQ triggered HR, promoted Nrf2 transfer into the cell nucleus and induced cell apoptosis, while Nrf2 deficient elevated cell apoptosis, attenuated the expression of PARP1 and RAD51. We also observed that Nrf2 deficient triggered Caspase-9. Thus, we speculated that Nrf2 might participate in HQ-induced cell apoptosis through Caspase-9 dependent pathways. Meanwhile, Nrf2 participated in HQ-induced DNA damage repair by regulating the level of PARP1 and RAD51.</p></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"100 ","pages":"Article 105901"},"PeriodicalIF":2.6,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141728305","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}