Toxicology Research最新文献

筛选
英文 中文
Microsampling in toxicology studies - maximising the scientific, business and 3Rs advantages.
IF 2.2 4区 医学
Toxicology Research Pub Date : 2025-03-31 eCollection Date: 2025-04-01 DOI: 10.1093/toxres/tfaf045
Helen Prior, Adeyemi O Adedeji, Romalie Allen, Derek Angus, Daniel Baker, Hollie Blunt, David Coleman, Helen-Marie Dunmore, Elisa Passini, Tara Putnam, Marie-Luce Rosseels, Neil Spooner, Jane Stewart, Carol Strepka, Alan Stokes, Tom Verhaeghe, Amanda Wilson, Fiona Sewell
{"title":"Microsampling in toxicology studies - maximising the scientific, business and 3Rs advantages.","authors":"Helen Prior, Adeyemi O Adedeji, Romalie Allen, Derek Angus, Daniel Baker, Hollie Blunt, David Coleman, Helen-Marie Dunmore, Elisa Passini, Tara Putnam, Marie-Luce Rosseels, Neil Spooner, Jane Stewart, Carol Strepka, Alan Stokes, Tom Verhaeghe, Amanda Wilson, Fiona Sewell","doi":"10.1093/toxres/tfaf045","DOIUrl":"10.1093/toxres/tfaf045","url":null,"abstract":"<p><p>Adoption of a blood microsampling technique can reduce or avoid the use of satellite animals (rodents) for toxicokinetics or other purposes in discovery and toxicology studies and provides refinements applicable for both rodents and larger animals. Microsampling can increase the scientific value of data obtained from rodent studies during drug and (agro)chemical development, enabling multiple endpoints to be investigated and compared in an individual animal in the same way as non-rodents. A cross-sector survey was developed to understand the current use of microsampling in toxicology studies, with the aim of identifying the specific studies in which microsampling was employed and the barriers to wider uptake. A high proportion of the survey responses indicated that microsampling was used, however, the extent varied widely. Some organisations use the technique only in non-GLP studies. Microsampling was used most for pharmacokinetics or toxicokinetics, commonly within small molecule and agrochemical toxicity studies, but less frequently within large molecule, cell/gene therapies or industrial chemical studies. A wide variety of barriers to wider use of microsampling were provided, typically around reticence to change from using larger samples, or not wishing to validate another bioanalytical method given the resources and challenges associated with the validation of a new technology. Despite these barriers, some organisations have adopted microsampling routinely across many/all rodent toxicity studies and there are opportunities to further reduce and refine animal use across all sectors by wider adoption of microsampling.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 2","pages":"tfaf045"},"PeriodicalIF":2.2,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Protective effects of corn silk and asparagus Officinalis against formaldehyde-induced reproductive toxicity in male rats via CDK2/Spem1/Fbxo47 and Tet1 pathways.
IF 2.2 4区 医学
Toxicology Research Pub Date : 2025-03-27 eCollection Date: 2025-04-01 DOI: 10.1093/toxres/tfaf039
Amina Zedan, Mohamed H Abdelfattah, Eman S El-Gezawy, Asmaa M El-Gawish, Amira M El-Moslemany, Neveen M Zeima, Ibrahim Albokhadaim, Sameer Alhojaily, Heba I Ghamry, Badriyah S Alotaibi, Mohamed Marzok, Mustafa Shukry
{"title":"Protective effects of corn silk and <i>asparagus Officinalis</i> against formaldehyde-induced reproductive toxicity in male rats via CDK2/Spem1/Fbxo47 and Tet1 pathways.","authors":"Amina Zedan, Mohamed H Abdelfattah, Eman S El-Gezawy, Asmaa M El-Gawish, Amira M El-Moslemany, Neveen M Zeima, Ibrahim Albokhadaim, Sameer Alhojaily, Heba I Ghamry, Badriyah S Alotaibi, Mohamed Marzok, Mustafa Shukry","doi":"10.1093/toxres/tfaf039","DOIUrl":"10.1093/toxres/tfaf039","url":null,"abstract":"<p><p>This study investigated the protective effects of aqueous extracts of <i>Asparagus officinalis</i> and Corn Silk (<i>Stigma maydis</i>) against formaldehyde-induced reproductive toxicity in male albino rats. High-Performance Liquid Chromatography (HPLC) analysis revealed that Gallic acid was the major phenolic component in Corn Silk, while Syringic acid predominated in <i>A. officinalis</i>. Formaldehyde exposure significantly reduced (<i>P</i> < 0.05) body and testicular weights, reproductive hormone levels, sperm count, motility, and normal sperm morphology. It also caused notable histological changes and downregulated fertility-related genes (<i>CDK2, Spem1, Fbxo47,</i> and <i>Tet1</i>). Treatment with the plant extracts, especially at higher concentrations, significantly (<i>P</i> < 0.05) reversed these adverse effects, improved antioxidant status, and reduced tumor necrosis factor-α levels. These findings emphasize the potential applications of <i>A. officinalis</i> and Corn Silk extracts as natural toxicological agents, particularly for mitigating formaldehyde-induced reproductive toxicity. Additionally, their prospective role in fertility treatment underscores their potential to support reproductive health through natural, plant-based interventions.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 2","pages":"tfaf039"},"PeriodicalIF":2.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Royal jelly and doxorubicin suppressed tumor cells in the xenograft model of lung cancer via the STAT3/FOXM1/ATG7 signaling pathways in athymic nude mice: a biochemical, immunohistochemically and molecular approach.
IF 2.2 4区 医学
Toxicology Research Pub Date : 2025-03-27 eCollection Date: 2025-04-01 DOI: 10.1093/toxres/tfaf042
Tianying Du, Wanjun Wang, Rui Zhang
{"title":"Royal jelly and doxorubicin suppressed tumor cells in the xenograft model of lung cancer via the STAT3/FOXM1/ATG7 signaling pathways in athymic nude mice: a biochemical, immunohistochemically and molecular approach.","authors":"Tianying Du, Wanjun Wang, Rui Zhang","doi":"10.1093/toxres/tfaf042","DOIUrl":"10.1093/toxres/tfaf042","url":null,"abstract":"<p><p>Royal Jelly (RJ), a traditional medicinal compound with tumor-suppressive properties, was investigated for its antitumor effects on non-small cell lung cancer (NSCLC) using a mouse xenograft model. Fifty athymic nude mice were divided into five groups: a control group, an untreated NSCLC group, a doxorubicin (DOX)-treated group, an RJ-treated group, and a combined RJ + DOX treatment group. RJ was administered at 200 mg/kg/day by gavage, while DOX was given intraperitoneally at 80 mg/kg on days 10, 20, and 30. Tumor size, volume, and weight were monitored, and Kaplan-Meier analysis assessed survival. Biochemical and histopathological analyses showed that RJ modulated oxidative stress markers, reduced inflammation (IL-6, TNF-α, IL-8, interferon-γ), and inhibited tumor growth. RJ downregulated STAT3/FOXM1/ATG7 signaling pathways involved in tumor cell survival, proliferation, and metastasis. Additionally, RJ promoted mitochondrial apoptosis through increased p53 expression and reduced angiogenesis by suppressing VEGF. Immunohistochemistry revealed decreased Ki-67 expression, indicating reduced tumor cell proliferation. Molecular analyses confirmed RJ's role in modulating key apoptosis and angiogenesis pathways. When combined with DOX, RJ enhanced therapeutic efficacy, suggesting a synergistic effect. These findings highlight RJ's potential as a therapeutic agent targeting STAT3 and related pathways in NSCLC treatment, offering a promising complementary approach to conventional chemotherapy.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 2","pages":"tfaf042"},"PeriodicalIF":2.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Antioxidant, anti-inflammatory and Uroprotective effects of LAMOTRIGINE Cinnamaldehyde silver complex in cyclophosphamide-induced cystitis.
IF 2.2 4区 医学
Toxicology Research Pub Date : 2025-03-27 eCollection Date: 2025-04-01 DOI: 10.1093/toxres/tfaf041
Irfan Anjum, Syeda Kainat Zahra, Kashif Barkat, Muhammad Naveed Mushtaq, Mushtaq Ahmad Ansari, Saima Najam, Shah Jahan, Sophia Awais, Kishwar Sultana, Nadia Bibi, Saira Khan, Tariq Nadeem
{"title":"Antioxidant, anti-inflammatory and Uroprotective effects of LAMOTRIGINE Cinnamaldehyde silver complex in cyclophosphamide-induced cystitis.","authors":"Irfan Anjum, Syeda Kainat Zahra, Kashif Barkat, Muhammad Naveed Mushtaq, Mushtaq Ahmad Ansari, Saima Najam, Shah Jahan, Sophia Awais, Kishwar Sultana, Nadia Bibi, Saira Khan, Tariq Nadeem","doi":"10.1093/toxres/tfaf041","DOIUrl":"10.1093/toxres/tfaf041","url":null,"abstract":"<p><p>Cyclophosphamide (CYP)-induced cystitis is a significant clinical challenge in cancer patients, characterized by inflammation, oxidative stress, and muscle dysfunction. This study aimed to investigate the protective effects of lamotrigine cinnamaldehyde silver complex (LCSC) against CYP-induced cystitis. Sprague-Dawley rats were divided into six groups: Control, CYP-induced cystitis (Disease Control), mesna (standard drug), and three LCSC treatment groups (2.5, 5, and 10 mg/kg). Nociception, open-field test, bladder weight, edema, hemorrhage, vascular permeability, histopathological analysis, and the qRT-PCR expression of inflammatory and antioxidant genes were investigated. Molecular docking was performed using AutoDock Tools 1.5.6 software. LCSC treatment significantly reduced nociceptive responses and improved locomotor activity in a dose-dependent manner compared to the diseased control group. LCSC attenuated CYP-induced increases in bladder weight, edema, and hemorrhage. The higher doses of LCSC (5 and 10 mg/kg) were more effective in reducing vascular permeability. In vitro studies revealed that LCSC relaxed the urinary bladder strips in a concentration-dependent manner. LCSC also significantly upregulated the expression of antioxidant genes (catalase and superoxide dismutase) and downregulated inflammatory markers (inducible nitric oxide synthase, tumor necrosis factor-α, and transforming growth factor-β) in a dose-dependent manner. The histopathological evaluation confirmed the preservation of bladder architecture in LCSC-treated rats. LCSC demonstrated strong binding affinities and lower inhibition constants with key inflammatory and muscle protein receptors, including IL-1β, TNF-α, MLCP, and PKC, compared to Mesna. LCSC exhibited potent antioxidant, anti-inflammatory, and uroprotective effects in the CYP-induced rat model of cystitis as a potential therapeutic drug.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 2","pages":"tfaf041"},"PeriodicalIF":2.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effects and regulatory mechanisms of bisphenol a on the increases apoptosis and decreases differentiation potential in mouse embryonic stem cells.
IF 2.2 4区 医学
Toxicology Research Pub Date : 2025-03-27 eCollection Date: 2025-04-01 DOI: 10.1093/toxres/tfaf043
Cheng-Kai Lee, Fu-Ting Wang, Chien-Hsun Huang, Hsin-Ju Lin, Wen-Hsiung Chan
{"title":"Effects and regulatory mechanisms of bisphenol a on the increases apoptosis and decreases differentiation potential in mouse embryonic stem cells.","authors":"Cheng-Kai Lee, Fu-Ting Wang, Chien-Hsun Huang, Hsin-Ju Lin, Wen-Hsiung Chan","doi":"10.1093/toxres/tfaf043","DOIUrl":"10.1093/toxres/tfaf043","url":null,"abstract":"<p><p>Bisphenol A has deleterious effects on reproductive, developmental, cell biological, and physiological functions. Here, we investigated the dosage effects of bisphenol A on the differentiation potential and apoptosis of mouse embryonic stem cells, and assessed some relevant regulatory mechanisms. Our results showed that bisphenol A at doses of 1-2 μmol/L triggers apoptotic processes without necrotic cell death in the ESC-B5 mouse embryonic stem cell line. No death effect was seen at treatment dosages of 0.5 μmol/L or less. Mechanistically, the application of 1-2 μmol/L bisphenol A directly increased the intracellular oxidative stress levels, significantly increased the cytoplasmic calcium and nitric oxide contents, decreased the mitochondrial membrane potential, activated caspases-9 and -3, and triggered programmed cell death. Interestingly, embryoid body formation assays showed that 0.5 μmol/L bisphenol A decreased the differentiation potential of ESC-B5 cells without inducing apoptotic processes. Together, our results indicate that treatment with 1-2 μmol/L bisphenol A induces apoptosis and triggers hazardous effects on the differentiation and developmental potential of mouse embryonic stem cells in vitro<i>.</i> These results provide important evidence that bisphenol A should be considered a potent cytotoxin that has dose-dependent impacts on differentiation and apoptosis in a mouse embryonic stem cell line.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 2","pages":"tfaf043"},"PeriodicalIF":2.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11950671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Meta-analysis of studies testing the association between air pollution and live birth rates in women undergoing assisted reproductive technology.
IF 2.2 4区 医学
Toxicology Research Pub Date : 2025-02-27 eCollection Date: 2025-02-01 DOI: 10.1093/toxres/tfaf028
Juan Hu, Huiqiu Zheng, Yan Wu, Qing Yan, Minghao Zhang, Shikun Sun, Meidi Gong, Rao Zheng, Shujing Jia, Rui Zhou, Jing Wu
{"title":"Meta-analysis of studies testing the association between air pollution and live birth rates in women undergoing assisted reproductive technology.","authors":"Juan Hu, Huiqiu Zheng, Yan Wu, Qing Yan, Minghao Zhang, Shikun Sun, Meidi Gong, Rao Zheng, Shujing Jia, Rui Zhou, Jing Wu","doi":"10.1093/toxres/tfaf028","DOIUrl":"10.1093/toxres/tfaf028","url":null,"abstract":"<p><p>Amidst a proliferation of research on air pollutants and negative pregnancy outcomes, uncertainty lingers regarding their impact on live birth rates in women receiving assisted reproductive technology (ART). This meta-analysis aims to clarify this vital issue. We searched EMBASE, PubMed, and Web of Science databases, targeting articles published prior to 2023 August 2. We pooled relative risks (RRs) and their corresponding 95% confidence intervals (95%CIs) across all included studies to assess the relationship between exposure to air pollutants and live birth rates. From an initial 5,785 citations, we identified five eligible papers with a total sample size of approximately 282,000 participants. In the year prior to oocyte retrieval, for every 10 μg/m<sup>3</sup> increase in fine particulate matter (PM<sub>2.5</sub>) (RR: 0.94, 95%CI: 0.92-0.97) and coarse particulate matter (PM<sub>10</sub>) (RR: 0.95, 95%CI: 0.92-0.97), the probability of live birth decreased by 6% and 5%, respectively. For every additional ppb increase in nitrogen dioxide (NO<sub>2</sub>) (RR: 0.92, 95%CI: 0.87-0.98), the likelihood of live birth decreased by 8%. This meta-analysis demonstrates adverse associations between air pollution and live birth rates in women undergoing ART. These findings highlight further elucidate the observed associations, as well as to explore potential mechanisms and implications for reproductive health.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfaf028"},"PeriodicalIF":2.2,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Comparative in vitro and in silico evaluation of the toxic effects of metformin and/or ascorbic acid, new treatment options in the treatment of Melasma.
IF 2.2 4区 医学
Toxicology Research Pub Date : 2025-02-27 eCollection Date: 2025-02-01 DOI: 10.1093/toxres/tfaf025
Hülya Tezel Yalçın, Deniz Arca Çakır, Anıl Yirün, Sonia Sanajou, Gözde Işık, Özlem Bozdemir, İbrahim Özçelik, Merve Güdül Bacanlı, Naciye Dilara Zeybek, Terken Baydar, Pınar Erkekoğlu
{"title":"Comparative in vitro and in silico evaluation of the toxic effects of metformin and/or ascorbic acid, new treatment options in the treatment of Melasma.","authors":"Hülya Tezel Yalçın, Deniz Arca Çakır, Anıl Yirün, Sonia Sanajou, Gözde Işık, Özlem Bozdemir, İbrahim Özçelik, Merve Güdül Bacanlı, Naciye Dilara Zeybek, Terken Baydar, Pınar Erkekoğlu","doi":"10.1093/toxres/tfaf025","DOIUrl":"10.1093/toxres/tfaf025","url":null,"abstract":"<p><p>Melasma is a chronic condition that leads to the buildup of melanin pigment in the epidermis and dermis due to active melanocytes. Even though it is considered a non-life-threatening condition, pigment disorders have a negative impact on quality of life. Since melasma treatment is not sufficient and complicated, new treatment options are sought. Research on metformin and ascorbic acid suggested that they might be used against melasma in the scope of \"drug repositioning.\"The MNT-1 human melanoma cell line was used to assess the effects of metformin, ascorbic acid, and metformin+ascorbic acid combination on cytotoxicity and oxidative stress. Melanin, cAMP, L-3,4-dihydroxyphenylalanine (L-DOPA) and tyrosinase levels were determined by commercial ELISA kits and tyrosinase gene expression was analyzed with RT-qPCR. Cytopathological evaluations were performed by phase contrast microscopy. Tyrosinase expression was determined by immunofluorescence (IF) staining of MNT-1 cells. The online service TargetNet was used for biological target screening. The parameters were not significantly altered by ascorbic acid applied at non-cytotoxic concentrations. On the contrary, metformin dramatically raised tyrosinase and intracellular ROS levels. Moreover, intracellular ROS levels and tyrosinase levels were found to be considerably elevated with the combined treatment. Also, potential metformin and ascorbic acid interactions were determined. According to the results, it can be said that these parameters were not significantly altered by ascorbic acid. On the contrary, metformin dramatically raised tyrosinase and intracellular oxidative stress levels. Moreover, intracellular oxidative stress and tyrosinase levels were elevated with the combined treatment. In conclusion, individual treatments of ascorbic acid or metformin may only provide a limited effect when treating melasma and extensive in vitro and in vivo research are required.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfaf025"},"PeriodicalIF":2.2,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Toxicity assessment of imatinib mesylate and a related impurity: in vitro and in vivo approaches.
IF 2.2 4区 医学
Toxicology Research Pub Date : 2025-02-26 eCollection Date: 2025-02-01 DOI: 10.1093/toxres/tfaf029
Cássia Franciele Rosa da Silva Rocha, Bruna Saraiva Hermmann, Juliana Machado Kayser, Gabriela Zimmermann Prado Rodrigues, Günther Gehlen, Fernanda Brião Menezes Boaretto, Jaqueline Nascimento Picada, Juliane Deise Fleck, Mariele Feiffer Charão, Simone Gasparin Verza
{"title":"Toxicity assessment of imatinib mesylate and a related impurity: in vitro and in vivo approaches.","authors":"Cássia Franciele Rosa da Silva Rocha, Bruna Saraiva Hermmann, Juliana Machado Kayser, Gabriela Zimmermann Prado Rodrigues, Günther Gehlen, Fernanda Brião Menezes Boaretto, Jaqueline Nascimento Picada, Juliane Deise Fleck, Mariele Feiffer Charão, Simone Gasparin Verza","doi":"10.1093/toxres/tfaf029","DOIUrl":"10.1093/toxres/tfaf029","url":null,"abstract":"<p><p>Imatinib mesylate (IM) is a widely used anticancer drug, mainly for treating chronic myeloid leukemia. However, pharmaceutical formulations may contain impurities, which in some cases can be more toxic than the parent compounds. This study aimed to compare the toxicity of IM and one of its impurities (IMP), N-(2-methyl-5-aminophenyl)-4-(3-pyridyl)-2-pyrimidine amine, using progressively complex models. Cytotoxicity was evaluated using 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium, neutral red uptake and sulforhodamine B colorimetric assays. Mutagenic activity was assessed using the Ames test<i>.</i> In vivo assays were performed using both the invertebrate <i>C. elegans</i> and vertebrate zebrafish embryo models. In Vero cell cultures, the cytotoxicity of IM and IMP was found to be similar across the colorimetric assays tested. Neither IM nor IMP showed mutagenic effects in the Ames test. In the <i>C. elegans</i> lethality and development assay the toxicity profiles of the compounds were similar. However, in the Fish Embryo Acute Toxicity assay, the LC<sub>50</sub> value for IMP (0.735 μg/mL) was significantly lower than that for IM (60.86 μg/mL), indicating greater toxicity for IMP. Furthermore, sublethal effects such as yolk-sac edema, pericardial edema, and tail deformities, were observed in embryos treated with IMP, even at low concentrations, indicating potential hazards associated with IMP. This study is the first to evaluate the toxicity of an IM subproduct, previously reported in pharmaceutical formulations, using different models. The Zebrafish model demonstrated higher sensitivity in predicting the toxic response of the TKI subproduct.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfaf029"},"PeriodicalIF":2.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The effect and mechanism of atorvastatin regulating PI3K-Akt-mTOR pathway on radiosensitivity of hepatocellular carcinoma cells.
IF 2.2 4区 医学
Toxicology Research Pub Date : 2025-02-25 eCollection Date: 2025-02-01 DOI: 10.1093/toxres/tfae202
Zhengzheng Deng, Jinjing Guo, Zihao Zhu, Qiancheng Qing, Dangting Wan, Pengyuan Lei, Qi Liu, Bo Huang
{"title":"The effect and mechanism of atorvastatin regulating PI3K-Akt-mTOR pathway on radiosensitivity of hepatocellular carcinoma cells.","authors":"Zhengzheng Deng, Jinjing Guo, Zihao Zhu, Qiancheng Qing, Dangting Wan, Pengyuan Lei, Qi Liu, Bo Huang","doi":"10.1093/toxres/tfae202","DOIUrl":"10.1093/toxres/tfae202","url":null,"abstract":"<p><p>Radiation therapy is an important method to treat liver cancer, but because of the strong DNA repair ability of liver cancer cells, even after receiving high doses of radiation still can not get satisfactory results. Atorvastatin (ATO) is a lipophilic and tissue-selective inhibitor of HMG-CoA reductase whose anticancer effects have been validated in various cells, but its effect on the radiation sensitivity of hepatocellular carcinoma cells remains unclear. Therefore, Therefore, this study explored the radiosensitivity of ATO and its possible mechanism by pretreating HepG2 with ATO and collecting HepG2 cells after irradiation. It was found that atorvastatin can not only affect the survival of liver cancer cells when used alone, but also enhance the radiation sensitivity of HepG2 cells. The study found that ATO significantly exacerbated the inhibitory effects of IR on the growth, proliferation, and migration of HepG2 cells. Measurement of ROS, SOD, GPx, and MDA levels indicated that ATO enhanced IR-induced oxidative stress, further promoted the decrease of Mitochondrial Membrane Potential, increased the rate of apoptosis in HepG2, upregulating pro-apoptotic proteins Bax and Cleaved-Caspase 3, and downregulating anti-apoptotic proteins Bcl-2. Western blot analysis showed that the PI3K-Akt-mTOR pathway was inhibited, leading to the activation of cytotoxic autophagy in HepG2 and an increase in the expression of the LC-3II protein. In summary, ATO, in combination with IR, enhances the oxidative stress response of HepG2 induced by IR, promotes autophagy by inhibiting the PI3K-Akt-mTOR pathway, and thereby potentially enhances the radiosensitivity of HepG2 as a pharmacological intervention.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfae202"},"PeriodicalIF":2.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11851483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Editorial.
IF 2.2 4区 医学
Toxicology Research Pub Date : 2025-02-24 eCollection Date: 2025-02-01 DOI: 10.1093/toxres/tfaf018
Shirley Price
{"title":"Editorial.","authors":"Shirley Price","doi":"10.1093/toxres/tfaf018","DOIUrl":"https://doi.org/10.1093/toxres/tfaf018","url":null,"abstract":"","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 1","pages":"tfaf018"},"PeriodicalIF":2.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11848837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143497730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信