Toxicology in Vitro最新文献

{"title":"Effects of 17β-estradiol and estrogen receptor subtype-specific agonists on Jurkat E6.1 T-cell leukemia cells","authors":"Rahul S. Nair ,&nbsp;Mantavya N. Patel ,&nbsp;Thangamani Kannan ,&nbsp;Shaili Gour ,&nbsp;Murali M. Hariharan ,&nbsp;Vijayarengamani Prasanna ,&nbsp;Anupriya Thirumalai ,&nbsp;Ramanathan Chockalingam ,&nbsp;Ramasamy Vasantharekha ,&nbsp;Srinivasan ThyagaRajan ,&nbsp;Hannah P. Priyanka","doi":"10.1016/j.tiv.2025.106057","DOIUrl":"10.1016/j.tiv.2025.106057","url":null,"abstract":"<div><h3>Background</h3><div>Estrogen signaling plays a crucial role in immune regulation and cancer metabolism, yet its impact on T-cell leukemia remains unclear. In hematological malignancies, estrogen receptor (ER) activation may influence metabolic shifts that affect cell survival and proliferation. This study investigates the <em>in vitro</em> effects of 17β-estradiol and estrogen receptor subtype-specific agonists on Jurkat E6.1 T-cell leukemia cells.</div></div><div><h3>Purpose</h3><div>To assess how estrogen signaling influences metabolic reprogramming, inflammatory response, and survival pathways in Jurkat E6.1 cells through receptor-dependent and independent mechanisms.</div></div><div><h3>Methods</h3><div>Jurkat E6.1 cells incubated with different concentrations of 17β-estradiol (10⁻¹² M, 10⁻¹⁰ M, 10⁻⁸ M) or ER-α agonist 4,4′,4″-(4-Propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol (10⁻¹⁰ M, 10⁻⁸ M, 10⁻⁶ M) or ER-β agonist diarylproprionitrile (10⁻¹⁰ M, 10⁻⁸ M, 10⁻⁶ M) with and without non-specific antagonist ICI 182,780 (10⁻⁶ M). The metabolic enzyme activities of hexokinase, pyruvate kinase, and citrate synthase were measured in cell pellets, while supernatants were analyzed for IL-6 and nitric oxide (NO) production. Additionally, PI3K/Akt pathway activation was assessed by measuring p-Akt/Total Akt expression.</div></div><div><h3>Results</h3><div>A shift from glycolysis to oxidative phosphorylation was observed on treatment with 17β-estradiol with significant decline in hexokinase activity and a concomitant increase in activities of pyruvate kinase and citrate synthase.</div></div><div><h3>Conclusion</h3><div>17β-estradiol mediates its effects on Jurkat E6.1 cells <em>in vitro</em> through receptor-subtype dependent and independent mechanisms involving metabolic enzymes (hexokinase, pyruvate kinase, citrate synthase), cytokines (IL-6), nitric oxide, and signaling molecules (p-Akt).</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"106 ","pages":"Article 106057"},"PeriodicalIF":2.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671592","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":"Inhibition of JAK2/STAT3 by pacritinib synergizes with chemotherapy in esophageal carcinoma","authors":"Lan Han ,&nbsp;Yinyin Sun ,&nbsp;Kai Yang,&nbsp;Cheng Long","doi":"10.1016/j.tiv.2025.106056","DOIUrl":"10.1016/j.tiv.2025.106056","url":null,"abstract":"<div><div>The poor outcomes associated with esophageal carcinoma, particularly in advanced stages, necessitate the development of new treatment strategies. This study examines the efficacy of pacritinib, a multi-kinase inhibitor, both alone and in combination with carboplatin, in preclinical esophageal carcinoma models. Six esophageal carcinoma cell lines (KYSE-70, OE33, FLO-1, KYAE-1, ESO 26, and HCE-6) were treated with pacritinib, resulting in a dose-dependent reduction in cell viability. Combination index (CI) analysis demonstrated strong synergy between pacritinib and carboplatin across this panel of cell lines. In in vivo esophageal carcinoma xenograft model, pacritinib alone significantly reduced tumor growth and improved survival rates compared to control. Notably, the combination of pacritinib and carboplatin further reduced tumor growth and improved survival rates compared to either treatment alone. Toxicity assessment showed that neither single-agent nor combination treatment resulted in significantly altered levels of body weight and serum markers, supporting the safety profile of pacritinib in combination with carboplatin. Mechanistic studies revealed that while pacritinib inhibited the phosphorylation of JAK, STAT3, and IRAK1 in esophageal carcinoma cells, it is the suppression of the JAK/STAT3 pathway, rather than IRAK1, that is responsible for the synergistic effect with carboplatin. Our findings indicate that pacritinib possesses potent anti-tumor activity in esophageal carcinoma and enhances the efficacy of carboplatin through the suppression of JAK/STAT3 signaling, warranting further clinical investigation.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"106 ","pages":"Article 106056"},"PeriodicalIF":2.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143671597","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":"Assessment of intestinal absorption of five cannabinoids from an ethanolic CBD-rich hemp extract using Caco-2 cells in vitro","authors":"Magali Araujo,&nbsp;Erica Stewart,&nbsp;Yang Zhao,&nbsp;Estatira Sepehr,&nbsp;Cory Vaught,&nbsp;Clara Erice,&nbsp;Robert L. Sprando","doi":"10.1016/j.tiv.2025.106053","DOIUrl":"10.1016/j.tiv.2025.106053","url":null,"abstract":"<div><div>Cannabinoids are highly lipophilic constituents of the hemp plant, which is present in several products intended for consumption. While cannabidiol (CBD) effects to humans have been extensively investigated, there is limited information on other minor cannabinoids. CBD oral bioavailability is low but increases with food and high-fat intake. We used Caco-2 cells <em>in vitro</em> to assess intestinal absorption of five cannabinoids (CBD, CBC, CBG, CBN, and CBDV) present in a CBD-rich hemp extract. We used a fed-state simulated intestinal fluid (Fessif) for dissolution of cannabinoids. Cannabinoids did not alter Caco-2 monolayer integrity. Except for CBC, recovery of cannabinoids decreased significantly after 90-minute incubation, compared to 60-minute incubation. No measurable cannabinoids were identified in the bottom chambers. Recovery of CBD, CBC, CBG and CBN after incubation with hemp extract or cannabinoid mix containing 30 μM CBD was unchanged, but CBDV recovery decreased. With hemp extract or a mix containing 10 μM CBD, recovery of CBD and CBC did not change, CBG recovery was lower (80–82 %), and CBN and CBDV were unquantifiable. This study highlights the challenges of evaluating permeability of cannabinoids by Caco-2 cells to predict intestinal absorption, including the physicochemical properties of these compounds, incubation time and cell properties.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"106 ","pages":"Article 106053"},"PeriodicalIF":2.6,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143652047","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":"Development of skin corrosion and irritation test methods employing ex vivo porcine skin model","authors":"Jeong-hyun Hong ,&nbsp;Kyung-Min Lim","doi":"10.1016/j.tiv.2025.106055","DOIUrl":"10.1016/j.tiv.2025.106055","url":null,"abstract":"<div><div>Skin corrosion and irritation are key local toxicological responses of the skin to chemical exposure. Conventional <em>in vivo</em> methods have limitations such as species difference, ethical concern, and reproducibility issue, necessitating the development of reliable alternatives. We developed skin corrosion (SCT) and irritation test (SIT) methods using <em>ex vivo</em> porcine ear skin based on cell viability and skin barrier disruption. Test chemicals were treated on <em>ex vivo</em> porcine ear skin for 3 min and 60 min (SCT) or 60 min only (SIT). After 40 ± 2 h post-incubation, cell viability assay with CCK-8, and skin barrier test with FITC-dextran penetration were conducted. To evaluate the predictive capacity of the method, 38 reference chemicals (20 corrosives, 8 irritants and 10 no category chemicals) were tested. SCT achieved 96.7 % (29/30) accuracy in identifying corrosives, meeting the performance standards of OECD TG 431 <em>In Vitro</em> Skin Corrosion: Reconstructed Human Epidermis test. The accuracy for subcategorizing corrosive substances into categories 1 A (&lt;25 % at 3 min) and 1B/1C (≥25 % at 3 min, &lt;25 % at 60 min) was 83.3 % (25/30). The accuracy of SIT identifying non-irritant (≥50 % at 60 min) was 83.3 % (15/18). FITC-dextran penetration assay showed a similar accuracy, highlighting its value as an alternative endpoint to identify irritants. Collectively, this study demonstrated that the <em>ex vivo</em> porcine skin model may offer a cost-effective, and reliable alternative for skin hazard testing.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"106 ","pages":"Article 106055"},"PeriodicalIF":2.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639850","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":"Environmentally relevant concentrations of antimony pose potential risks to human health: An evaluation on human umbilical vein endothelial cells","authors":"Shanshan Wang ,&nbsp;Dongqian Guo ,&nbsp;Xian Chen ,&nbsp;Su-Zhu Chen ,&nbsp;Xi-Wen Cui ,&nbsp;Yong-He Han ,&nbsp;Ping Xiang","doi":"10.1016/j.tiv.2025.106054","DOIUrl":"10.1016/j.tiv.2025.106054","url":null,"abstract":"<div><div>Antimony (Sb) ore exploitation and the use of Sb-containing drugs pose known health risks. This study investigated the toxicity of environmentally relevant concentrations of Sb (0.12–12 mg L⁻¹) on human umbilical vein endothelial cells (HUVECs). The 50 % lethal concentration (LC₅₀) of Sb to HUVECs was 11.4 mg L⁻¹. Exposing to high level of Sb induced cell cycle arrest by altering the expression of cell cycle regulators, inhibiting the transitions of G₀/G₁ to S and S to G₂/M. At 1.2 mg L⁻¹ Sb, <em>CKD6</em> and <em>p21</em> expressions in HUVECs changed to 0.75 and 1.32 folds that of no-Sb control, respectively (<em>p</em> &lt; 0.01). At 12 mg L⁻¹ Sb, <em>CDK2</em>, <em>CKD6</em>, and <em>p27</em> expressions decreased by 1.54, 4.41, and 1.54 folds (<em>p</em> &lt; 0.001), while <em>p21</em> expression increased by 3.03 folds (<em>p</em> &lt; 0.001) as compared to control. Sb also led to cell apoptosis, evidenced by Annexin V-FITC/PI staining and changes in the expressions of <em>Bax</em> (1.21–1.30 folds, <em>p</em> &lt; 0.01) and <em>Bcl-2</em> (0.65–0.83 folds). Oxidative damage was a pivotal factor driving cell apoptosis, probably through down-regulating antioxidant genes (<em>CAT</em>, <em>GPX1</em>, and <em>GSTP1</em>) and up-regulating stress response genes (<em>HO-1</em>, <em>SOD1</em>, and <em>TrxR1</em>). The elevated H₂O₂ generated in mitochondria likely contributed to cell apoptosis due to the imbalance in H₂O₂ metabolism. These findings suggest that environmentally relevant concentrations of Sb can exert cytotoxicity to HUVECs, which should be of potential concern for human cardiovascular disease.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"106 ","pages":"Article 106054"},"PeriodicalIF":2.6,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628996","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":"Prolonged exposure to simvastatin affects coenzyme Q9/10 status leading to impaired mitochondrial respiratory capacity and reduced viability of cultured cardiac cells","authors":"Sinenhlanhla X.H. Mthembu ,&nbsp;Sithandiwe E. Mazibuko-Mbeje ,&nbsp;Sonia Silvestri ,&nbsp;Patrick Orlando ,&nbsp;Bongani B. Nkambule ,&nbsp;Christo J.F. Muller ,&nbsp;Luca Tiano ,&nbsp;Phiwayinkosi V. Dludla","doi":"10.1016/j.tiv.2025.106052","DOIUrl":"10.1016/j.tiv.2025.106052","url":null,"abstract":"<div><div>This study investigates the effects of prolonged simvastatin exposure on coenzyme Q_9/10 (CoQ_9/10) levels, an essential component of antioxidant defense, in cultured cardiac cells. Statins, commonly used to manage dyslipidemia and reduce cardiovascular risk, may impair mitochondrial function, but their impact on CoQ₁₀ depletion and oxidative stress is not well understood. We examined the influence of simvastatin on mitochondrial oxidative capacity, reactive oxygen species (ROS) production, and CoQ_9/10 status at concentrations of 0.3, 0.6, 1.25, 2.5, 5, 10, and 20 μM, over durations of 24, 48, and 72 h. Using an in vitro model of cultured H9c2 cardiomyoblasts, our results showed that short-term exposure (24 h) at lower concentrations (&lt;5 μM) enhanced cytosolic and mitochondrial ROS levels without affecting mitochondrial function or CoQ_9/10 status. However, prolonged exposure to higher concentrations (≥10 μM for &gt;48 h) resulted in impaired mitochondrial oxidative capacity, indicated by increased proton leak and elevated ROS levels, which were followed by significantly reduced cell viability. These findings suggest that prolonged, high-dose simvastatin exposure may disrupt the oxidative balance of CoQ_9/10, leading to myocardial injury. This research addresses a gap in understanding the long-term effects of statins on mitochondrial health and underscores the need for further studies to optimize statin therapy and minimize adverse effects on myocardial function.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"106 ","pages":"Article 106052"},"PeriodicalIF":2.6,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634996","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":"Effect of serotonin 7 receptors and transcript variants on RIN-5F pancreatic beta cell line","authors":"Muhammed Yayla ,&nbsp;Erdem Toktay ,&nbsp;Bengul Ozdemir Sarikaya ,&nbsp;Ugur Ermis ,&nbsp;Sakir Akgun ,&nbsp;Irfan Cinar","doi":"10.1016/j.tiv.2025.106050","DOIUrl":"10.1016/j.tiv.2025.106050","url":null,"abstract":"<div><h3>Purpose</h3><div>The physiological effects of 5-HT7 receptors expressed in pancreatic beta cells have not yet been elucidated. We first aimed to investigate the effect of 5-HT7 receptor agonist (AS19) and antagonist (SB269970) application on insulin secretion in RIN-5F pancreatic beta cells. Subsequently, we aimed to investigate the effects of agonist and antagonist applications on cell damage induced by STZ.</div></div><div><h3>Materials/Methods</h3><div>Cell damage was caused by giving 5 mM STZ solution to the cells for 12 h. The protective effects of 5-HT7 receptor agonist and antagonist on this subsequent damage were investigated. IGF-1, TNF-α, TGF-B1, NF-KB, Bax, Caspase 3, Caspase 9, 5-HT7, 5HT7x2, 5HT7x3 mRNA expression levels were compared between groups.</div></div><div><h3>Results</h3><div>While agonist application stimulates insulin secretion, the effect of the antagonist varies.SB269970 reduced oxidative stress and downregulated TNF-a, TGF-B1 and NF-KB expression and also prevented apoptosis by decreasing Bax, caspase 3 and 9 levels against STZ-induced beta cell damage.</div></div><div><h3>Conclusions</h3><div>The effect of 5-HT7 receptors on insulin secretion and their effects against STZ damage will be guiding for more detailed studies in the treatment of diabetes and related diseases in the future.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"106 ","pages":"Article 106050"},"PeriodicalIF":2.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628997","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":"High-throughput assay for predicting diarrhea risk using a 2D human intestinal stem cell-derived model","authors":"Colleen M. Pike ,&nbsp;James A. Levi ,&nbsp;Lauren A. Boone,&nbsp;Swetha Peddibhotla,&nbsp;Jacob Johnson,&nbsp;Bailey Zwarycz,&nbsp;Maureen K. Bunger,&nbsp;William Thelin,&nbsp;Elizabeth M. Boazak","doi":"10.1016/j.tiv.2025.106040","DOIUrl":"10.1016/j.tiv.2025.106040","url":null,"abstract":"<div><div>Gastrointestinal toxicities (GITs) in clinical trials often lead to dose-limitations that reduce drug efficacy and delay treatment optimization. Preclinical animal models do not accurately replicate human physiology, leaving few options for early detection of GITs, such as diarrhea, before human studies. Chemotherapeutic agents, known to cause clinical diarrhea, frequently target mitotic cells. Therefore, we hypothesized a model utilizing proliferative cell populations derived from human intestinal crypts would predict clinical diarrhea occurrence with high accuracy. Here, we describe the development of a diarrhea prediction assay utilizing RepliGut® Planar, a primary intestinal stem cell-derived platform. To evaluate the ability of this model to predict clinical diarrhea risk, we assessed toxicity of 30 marketed drugs by measuring cell proliferation (EdU incorporation), cell abundance (nuclei quantification), and barrier formation (TEER) in cells derived from three human donors. Dose response curves were generated for each drug, and the IC15 to Cmax ratio was used to identify a threshold for assay positivity. This model accurately predicted diarrhea potential, achieving an accuracy of 91 % for proliferation, 90 % for abundance, and 88 % for barrier formation. In vitro toxicity screening using primary proliferative cells may reduce clinical diarrhea and ultimately lead to safer and more effective treatments for patients.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"106 ","pages":"Article 106040"},"PeriodicalIF":2.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631048","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":"Cytotoxicity of ZnO nanoparticles in human melanocyte cells in the presence or absence of UV radiation: A preliminary comparative study with TiO2 nanoparticles","authors":"Karolina Niska ,&nbsp;Beata Muszyńska ,&nbsp;Szymon Kowalski ,&nbsp;Emilia Tomaszewska ,&nbsp;Magdalena Narajczyk ,&nbsp;Monika Pawłowska ,&nbsp;Paweł W. Majewski ,&nbsp;Ewa Augustin ,&nbsp;Iwona Inkielewicz-Stepniak","doi":"10.1016/j.tiv.2025.106051","DOIUrl":"10.1016/j.tiv.2025.106051","url":null,"abstract":"<div><div>Zinc oxide nanoparticles (ZnONPs) and titanium dioxide nanoparticles (TiO₂NPs), due to their nanometric size and photostability, are increasingly used as ingredients in sunscreens to absorb and scatter UV radiation. However, the current state of knowledge is insufficient to guarantee their safety. Therefore, the objectives of this study were to evaluate the cytotoxicity of ZnONPs and TiO₂NPs in the presence and absence of UV radiation in in vitro model of primary human melanocyte cells HEMas. Our research demonstrated that 47 nm TiO₂NPs exhibited lower toxicity compared to 25 nm ZnONPs. ZnONPs (5–12.5 ppm) affect various intracellular processes, including cell membrane integrity, proliferative processes, and the induction of morphological changes in cells at the ultrastructural level, particularly in mitochondria. The study highlights intricate mechanisms of cell death induced by ZnONPs, revealing a multifaceted interplay between apoptosis and necrosis. Additionally, we indicate the potential role of intracellular calcium ion influx, notably triggered by ZnONPs, in driving cell toxicity. This influx is linked to endoplasmic reticulum (ER) dysfunction, ultimately leading to cell death, offering valuable insights into the underlying mechanisms of nanoparticle-induced toxicity. Importantly, the co-exposure of both ZnONPs and TiO₂NPs with UV radiation (9 J/cm²) enhances the toxic effect on melanocyte cells, indicating an interaction between NPs and UV radiaton and raising potential concerns about their effects on melanocytes and overall skin health.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"106 ","pages":"Article 106051"},"PeriodicalIF":2.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143628998","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":"Genotoxicity of putrescine and its effects on gene expression in HepG2 cell line","authors":"Franco Dani Campos-Pereira ,&nbsp;Letícia Rocha Gonçalves,&nbsp;Raquel Vaz Hara Jardim,&nbsp;Letícia Bulascochi Cagnoni,&nbsp;Karen C.M. Moraes,&nbsp;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}