Toxicology in Vitro最新文献

{"title":"Cigarette sidestream smoke-induced cellular senescence and the protective role of histone H2AX","authors":"Yukako Komaki,&nbsp;Yuko Ibuki","doi":"10.1016/j.tiv.2025.106076","DOIUrl":"10.1016/j.tiv.2025.106076","url":null,"abstract":"<div><div>Cigarette smoke imposes serious health hazards such as cancer and cardiovascular diseases but is also associated with cellular senescence. Recently, histone loss and modifications are reported as one of the characteristics of cellular senescence. In this study, we examined the relationship between cigarette smoke-induced cellular senescence and histone H2A variant H2AX, an important player in DNA damage response. We exposed normal human skin diploid fibroblast ASF-4-1 to cigarette sidestream smoke (CSS) extract and successfully induced premature senescence. Persistent DNA damages are known to induce cellular senescence. Double strand breaks (DSBs) formation was detected in CSS-treated cells, indicating DSBs could be the cause for the CSS-induced cellular senescence. In the senescent cells, persistent phosphorylation of histone H2AX (γ-H2AX) and unexpected increase of H2AX protein expression was observed. To elucidate the role of H2AX in CSS-induced cellular senescence, we depleted H2AX in ASF-4-1 cells with siRNA. In H2AX-depleted cells, CSS-induced elevated β-galactosidase activity was more prominent. CSS concentration-dependent increase of reactive oxygen species and DSBs formation was also facilitated by H2AX depletion. These results suggest that histone H2AX may have a protective role against DNA damage-induced premature senescence.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"107 ","pages":"Article 106076"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891621","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":"The Alarming Consequences of Workforce Reductions at the FDA, EPA, NIH and CDC in the United States","authors":"","doi":"10.1016/j.tiv.2025.106077","DOIUrl":"10.1016/j.tiv.2025.106077","url":null,"abstract":"","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"107 ","pages":"Article 106077"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143913048","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 metabolic clearance of malathion in rats and humans","authors":"Gopinath Nallani ,&nbsp;Appavu Chandrasekaran ,&nbsp;Kelem Kassahun ,&nbsp;Li Shen ,&nbsp;Rick Reiss ,&nbsp;Paul Whatling","doi":"10.1016/j.tiv.2025.106080","DOIUrl":"10.1016/j.tiv.2025.106080","url":null,"abstract":"<div><div><em>In vitro</em> intrinsic clearance of malathion was determined in adult and juvenile rat and human liver microsomes. Due to rapid elimination with no detectable levels of the parent, clearance rates of malathion were calculated from formation kinetics of its metabolites: malathion monocarboxylic acid (MMCA) and malaoxon. To correlate <em>in vitro</em> data to <em>in vivo</em> exposure, pharmacokinetics (PK) study was performed in adult rats following a single <em>i.v.</em> (10 mg/kg bw) or oral dose (150 mg/kg bw). The <em>in vitro</em> kinetics data indicate that the metabolic clearance of malathion <em>via</em> formation of MMCA was at the same rate in adult and juvenile human liver microsomes (HLM), but in rat liver microsomes (RLM) the rate was about 10-fold higher in adults compared to juveniles. The rate of formation of malaoxon among the two species and age groups was within 3.5-fold difference. The formation kinetics of malaoxon represented &lt;0.5 % of that observed for MMCA in both rats and humans. As seen in the <em>in vitro</em> results, following <em>i.v.</em> or oral dosing in rats, malathion was not detectable with MMCA being the major metabolite. The kinetics data from this study were useful for the development of a PBPK model for malathion.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"107 ","pages":"Article 106080"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103114","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 Penthorum chinense pursh and gallic acid on embryonic and cardiac development in zebrafish (Danio rerio)","authors":"Kehui Liu ,&nbsp;Hui Jiang ,&nbsp;Rong Ji ,&nbsp;Yuanyuan Ma ,&nbsp;Rui Zhang ,&nbsp;Binbin Song ,&nbsp;Ying Han","doi":"10.1016/j.tiv.2025.106074","DOIUrl":"10.1016/j.tiv.2025.106074","url":null,"abstract":"<div><div><em>Penthorum chinense</em> Pursh (<em>P. chinense</em>), known for its anti-inflammatory and antioxidant properties, is valued for its low toxicity in animal and human models. However, concerns have arisen regarding the developmental effects of its bioactive components. This study investigates the acute toxicity of <em>P. chinense</em> extract and gallic acid on zebrafish embryos. The calculated LC₅₀ values were 237.0 mg/L for <em>P. chinense</em> extract and 328.4 mg/L for gallic acid, demonstrating a dose-response relationship with increasing mortality rates. Developmental assessments revealed significant morphological abnormalities, including heart defects, swim bladder and tail malformations, particularly at higher concentrations. Body length and eye diameter showed a hormetic dose-response to <em>P. chinense</em> extract, with increased growth at lower concentrations but a decrease at higher doses. Cardiac evaluations revealed altered heart rates, initially increasing and then decreasing at elevated concentrations. qRT-PCR analyses confirmed modulation of several heart-related genes, highlighting the differential impacts on cardiac development. These findings underscore the need to carefully assess the potential risks of <em>P. chinense</em> extract and gallic acid exposure in aquatic organisms.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"107 ","pages":"Article 106074"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864611","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":"Antibiotics reduce intestinal bile acid reuptake in an in vitro model system","authors":"Nina Zhang,&nbsp;Véronique M.P. de Bruijn,&nbsp;Weijia Zheng,&nbsp;Wouter Bakker,&nbsp;Bennard van Ravenzwaay,&nbsp;Ivonne M.C.M. Rietjens","doi":"10.1016/j.tiv.2025.106071","DOIUrl":"10.1016/j.tiv.2025.106071","url":null,"abstract":"<div><div>Enterohepatic circulation of bile acids is a highly efficient process that is important for bile acid homeostasis. The aim of the present study was to characterize the impact of a series of antibiotics (lincomycin, streptomycin, vancomycin and tobramycin) on the intestinal reuptake of conjugated bile acids (TCA, TCDCA, GCA and GCDCA) using a Caco-2 <em>in vitro</em> transwell model system. The results obtained demonstrate that both pre-exposure and co-exposure of the cells to an antibiotic and the bile acids, affected bile acid transport, to an extent that depended on the antibiotic, its concentration and the type of conjugated bile acid tested. Tobramycin, at concentrations in line with dose levels at which this antibiotic induced effects on bile acid homeostasis <em>in vivo</em>, appeared able to inhibit bile acid transport after pre-exposure of the cells, likely resulting from an effect on the expression of bile acid transporters <em>via</em> its effects on protein synthesis at ribosome level. Upon co-exposure of the Caco-2 cells to an antibiotic and the bile acids, all four antibiotics appeared to significantly reduce the transport of especially the conjugated bile acids TCDCA and GCDCA with a potency that decreased in the order vancomycin &gt; tobramycin = streptomycin &gt; lincomycin. The effects observed illustrate the possibility of using a new approach methodology (NAM) to study effects on intestinal bile acid reuptake.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"107 ","pages":"Article 106071"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844907","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":"Corrigendum to “Tetrazolium–based colorimetric assays underestimat the direct antitumor effects of bevacizumab” [Toxicology in vitro 91 (2023) 105631]","authors":"Pei Wei ,&nbsp;Min Wang ,&nbsp;Mao Lin ,&nbsp;Zhiyong Wang","doi":"10.1016/j.tiv.2025.106061","DOIUrl":"10.1016/j.tiv.2025.106061","url":null,"abstract":"","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"107 ","pages":"Article 106061"},"PeriodicalIF":2.6,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144042928","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":"The cyanobacterial toxins BMAA and 2,4-DAB perturb the l-serine biosynthesis pathway and induce systemic changes in energy metabolism in human neuroblastoma cells: A proteomic study","authors":"Lisa Pu ,&nbsp;Joel R. Steele ,&nbsp;Connor R. Phillips ,&nbsp;Jake P. Violi ,&nbsp;Kenneth J. Rodgers","doi":"10.1016/j.tiv.2025.106058","DOIUrl":"10.1016/j.tiv.2025.106058","url":null,"abstract":"<div><div>Blue-green algae (cyanobacteria), an ancient phylum of bacteria, produce a wide array of secondary metabolites that are toxic to humans. Rapid growth of cyanobacteria in an aquatic environment can result in algal blooms capable of turning waterways green and increasing toxin levels in the environment. Cyanobacterial toxins were first linked to the high incidence of a complex neurodegenerative disorder reported on the island of Guam in the 1940s but more recently have been linked to clusters of sporadic amyotrophic lateral sclerosis (sALS) worldwide. The non-protein amino acid β-<em>N</em>-methylamino-L-alanine (BMAA) and its isomer L-2,4-diaminobutyric acid (2,4-DAB) are produced concurrently by most cyanobacterial species. We carried out proteomic analysis on human neuroblastoma cells treated with BMAA and 2,4-DAB to determine the underlying mechanisms of toxicity resulting from exposure to these cyanotoxins and identified significant changes in the <span>l</span>-serine biosynthesis pathway as well as pathways associated with energy production in the cell such as fatty acid ß-oxidation and glycolysis. The impact on the serine biosynthetic pathway was supported by demonstrating a significant decrease in both mRNA and protein levels of the enzyme 3-phosphoglycerate dehydrogenase (PHGDH) the first committed step in serine biosynthesis. PHGDH uses 3-phospho-D-glycerate (3PG) an intermediate in the glycolytic pathway as a substrate, and co-incubation of cells with <span>l</span>-serine restored expression levels of PHGDH as did cell pre-treatment with the glycolytic product pyruvate. This is the first study to link exposure to BMAA and 2,4-DAB to impairments in the <span>l</span>-serine biosynthesis pathway and broad disturbances in energy metabolism.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"106 ","pages":"Article 106058"},"PeriodicalIF":2.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143735151","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":"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":"2025-06-01","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":"Glutaraldehyde-crosslinked Naringenin-loaded Albumin Nanoparticles (GNANPs) induce antimicrobial properties and apoptosis in gastric cancer cells","authors":"Murugan Alwarkurichi Munusamy ,&nbsp;Muruganantham Bharathi ,&nbsp;Abdullah A. Alarfaj ,&nbsp;Samer Hasan Hussein-Al-Ali ,&nbsp;Ravichandran Nagaiya ,&nbsp;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":"2025-06-01","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}

{"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":"2025-06-01","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}