{"title":"碘己醇对支气管上皮细胞的体外细胞遗传毒性及DNA和BCL-XL的亲和力研究。","authors":"Ibrahim Halil Kenger, Batuhan Bilgin","doi":"10.1002/jat.4800","DOIUrl":null,"url":null,"abstract":"<p><p>Iohexol is a nonionic contrast agent used in x-ray imaging but can sometimes cause anaphylactic reactions. The mechanism of anaphylaxis-induced fatal respiratory symptoms remains unclear. The aim of this study was to investigate the effects of iohexol on cytotoxicity and DNA damage in bronchial epithelial cells (BEAS-2B). BEAS-2B cells were treated with Iohexol (1.5, 15, 75, and 150 mg I/mL) and cell viability was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The IC<sub>50</sub> value of iohexol was determined and the DNA damage effect of iohexol (12.4, 24.9, 49.9, and 99.9 mM) on BEAS-2B cells was investigated by Comet assay. Molecular docking analysis was also performed to determine the binding affinity to DNA and the antiapoptotic protein BCL-XL. Iohexol 15 mg I/mL, iohexol 75 mg I/mL, and iohexol 150 mg I/mL groups significantly decreased cell viability compared to the control group (p < 0.0001). Iohexol (12.4, 24.9, 49.9, and 99.9 mM) did not significantly alter genotoxicity in BEAS-2B cells compared to the control group (p > 0.05). In silico study showed that iohexol binds with high affinity to BCL-XL but low affinity to DNA. Our results show that iohexol causes cytotoxicity in BEAS-2B cells and binds strongly to BCL-XL. Our results suggest that the safety of iohexol needs further detailed studies.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":" ","pages":""},"PeriodicalIF":2.8000,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"In Vitro Cytogenotoxicity of Iohexol in Bronchial Epithelial Cells and In Silico DNA and BCL-XL Affinity Studies.\",\"authors\":\"Ibrahim Halil Kenger, Batuhan Bilgin\",\"doi\":\"10.1002/jat.4800\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Iohexol is a nonionic contrast agent used in x-ray imaging but can sometimes cause anaphylactic reactions. The mechanism of anaphylaxis-induced fatal respiratory symptoms remains unclear. The aim of this study was to investigate the effects of iohexol on cytotoxicity and DNA damage in bronchial epithelial cells (BEAS-2B). BEAS-2B cells were treated with Iohexol (1.5, 15, 75, and 150 mg I/mL) and cell viability was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The IC<sub>50</sub> value of iohexol was determined and the DNA damage effect of iohexol (12.4, 24.9, 49.9, and 99.9 mM) on BEAS-2B cells was investigated by Comet assay. Molecular docking analysis was also performed to determine the binding affinity to DNA and the antiapoptotic protein BCL-XL. Iohexol 15 mg I/mL, iohexol 75 mg I/mL, and iohexol 150 mg I/mL groups significantly decreased cell viability compared to the control group (p < 0.0001). Iohexol (12.4, 24.9, 49.9, and 99.9 mM) did not significantly alter genotoxicity in BEAS-2B cells compared to the control group (p > 0.05). In silico study showed that iohexol binds with high affinity to BCL-XL but low affinity to DNA. Our results show that iohexol causes cytotoxicity in BEAS-2B cells and binds strongly to BCL-XL. Our results suggest that the safety of iohexol needs further detailed studies.</p>\",\"PeriodicalId\":15242,\"journal\":{\"name\":\"Journal of Applied Toxicology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-04-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Applied Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1002/jat.4800\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"TOXICOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Applied Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1002/jat.4800","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"TOXICOLOGY","Score":null,"Total":0}
In Vitro Cytogenotoxicity of Iohexol in Bronchial Epithelial Cells and In Silico DNA and BCL-XL Affinity Studies.
Iohexol is a nonionic contrast agent used in x-ray imaging but can sometimes cause anaphylactic reactions. The mechanism of anaphylaxis-induced fatal respiratory symptoms remains unclear. The aim of this study was to investigate the effects of iohexol on cytotoxicity and DNA damage in bronchial epithelial cells (BEAS-2B). BEAS-2B cells were treated with Iohexol (1.5, 15, 75, and 150 mg I/mL) and cell viability was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The IC50 value of iohexol was determined and the DNA damage effect of iohexol (12.4, 24.9, 49.9, and 99.9 mM) on BEAS-2B cells was investigated by Comet assay. Molecular docking analysis was also performed to determine the binding affinity to DNA and the antiapoptotic protein BCL-XL. Iohexol 15 mg I/mL, iohexol 75 mg I/mL, and iohexol 150 mg I/mL groups significantly decreased cell viability compared to the control group (p < 0.0001). Iohexol (12.4, 24.9, 49.9, and 99.9 mM) did not significantly alter genotoxicity in BEAS-2B cells compared to the control group (p > 0.05). In silico study showed that iohexol binds with high affinity to BCL-XL but low affinity to DNA. Our results show that iohexol causes cytotoxicity in BEAS-2B cells and binds strongly to BCL-XL. Our results suggest that the safety of iohexol needs further detailed studies.
期刊介绍:
Journal of Applied Toxicology publishes peer-reviewed original reviews and hypothesis-driven research articles on mechanistic, fundamental and applied research relating to the toxicity of drugs and chemicals at the molecular, cellular, tissue, target organ and whole body level in vivo (by all relevant routes of exposure) and in vitro / ex vivo. All aspects of toxicology are covered (including but not limited to nanotoxicology, genomics and proteomics, teratogenesis, carcinogenesis, mutagenesis, reproductive and endocrine toxicology, toxicopathology, target organ toxicity, systems toxicity (eg immunotoxicity), neurobehavioral toxicology, mechanistic studies, biochemical and molecular toxicology, novel biomarkers, pharmacokinetics/PBPK, risk assessment and environmental health studies) and emphasis is given to papers of clear application to human health, and/or advance mechanistic understanding and/or provide significant contributions and impact to their field.