Genotoxic effects of NDMA-contaminated ranitidine on Allium cepa cells and unveiling carcinogenic mechanisms via DFT and molecular dynamics simulation study
Abstract This study investigated the potential genotoxic and carcinogenic effects of N-nitrosodimethylamine (NDMA), a hazardous compound found in ranitidine formulations that are used to treat excessive stomach acid. The study first examined the effects of NDMA-contaminated ranitidine formulation on...
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Nature Portfolio
2024-12-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-82984-6 |
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| author | Mst. Kusum Kaly Md Ekhtiar Rahman Md. Sohel Rana Uzzal Kumar Acharjee Khondokar Nasirujjaman |
| author_facet | Mst. Kusum Kaly Md Ekhtiar Rahman Md. Sohel Rana Uzzal Kumar Acharjee Khondokar Nasirujjaman |
| author_sort | Mst. Kusum Kaly |
| collection | DOAJ |
| description | Abstract This study investigated the potential genotoxic and carcinogenic effects of N-nitrosodimethylamine (NDMA), a hazardous compound found in ranitidine formulations that are used to treat excessive stomach acid. The study first examined the effects of NDMA-contaminated ranitidine formulation on Allium cepa root growth and mitotic activity. The results demonstrated dose-dependent decreases in both root growth and mitotic index indicating genotoxicity and cell division disruption. Elevated concentrations of ranitidine correlated with increased chromosomal aberrations indicating genotoxic capabilities. These outcomes underscored that NDMA contaminated ranitidine exposure triggers genotoxicity hampering cell division and inducing chromosomal aberrations. Electronic characteristics of NDMA revealed its electrophilic nature suggesting its capability to create covalent adducts with DNA bases fostering genotoxic and carcinogenic characteristics. Molecular docking analysis showed the interactions of NDMA with DNA including hydrogen bonds and carbon-hydrogen interactions with nucleotide bases forming DNA adducts. Molecular dynamics simulations showcased the dynamic behavior of the DNA-NDMA complex over time with structural fluctuations. Dynamic hydrogen bond fluctuations implied interactive intricacies between solute and solvent molecules. Overall, this study illuminates how NDMA-contaminated ranitidine could trigger DNA damage and potentially contribute to carcinogenesis. It emphasizes the urgency of minimizing exposure to this perilous and hazardous compound. |
| format | Article |
| id | doaj-art-e12efba6d87c4e2bbb035bb5c19ad97f |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-e12efba6d87c4e2bbb035bb5c19ad97f2024-12-29T12:23:14ZengNature PortfolioScientific Reports2045-23222024-12-0114111410.1038/s41598-024-82984-6Genotoxic effects of NDMA-contaminated ranitidine on Allium cepa cells and unveiling carcinogenic mechanisms via DFT and molecular dynamics simulation studyMst. Kusum Kaly0Md Ekhtiar Rahman1Md. Sohel Rana2Uzzal Kumar Acharjee3Khondokar Nasirujjaman4Department of Genetic Engineering and Biotechnology, University of RajshahiDepartment of Genetic Engineering and Biotechnology, University of RajshahiDepartment of Genetic Engineering and Biotechnology, University of RajshahiDepartment of Genetic Engineering and Biotechnology, University of RajshahiDepartment of Genetic Engineering and Biotechnology, University of RajshahiAbstract This study investigated the potential genotoxic and carcinogenic effects of N-nitrosodimethylamine (NDMA), a hazardous compound found in ranitidine formulations that are used to treat excessive stomach acid. The study first examined the effects of NDMA-contaminated ranitidine formulation on Allium cepa root growth and mitotic activity. The results demonstrated dose-dependent decreases in both root growth and mitotic index indicating genotoxicity and cell division disruption. Elevated concentrations of ranitidine correlated with increased chromosomal aberrations indicating genotoxic capabilities. These outcomes underscored that NDMA contaminated ranitidine exposure triggers genotoxicity hampering cell division and inducing chromosomal aberrations. Electronic characteristics of NDMA revealed its electrophilic nature suggesting its capability to create covalent adducts with DNA bases fostering genotoxic and carcinogenic characteristics. Molecular docking analysis showed the interactions of NDMA with DNA including hydrogen bonds and carbon-hydrogen interactions with nucleotide bases forming DNA adducts. Molecular dynamics simulations showcased the dynamic behavior of the DNA-NDMA complex over time with structural fluctuations. Dynamic hydrogen bond fluctuations implied interactive intricacies between solute and solvent molecules. Overall, this study illuminates how NDMA-contaminated ranitidine could trigger DNA damage and potentially contribute to carcinogenesis. It emphasizes the urgency of minimizing exposure to this perilous and hazardous compound.https://doi.org/10.1038/s41598-024-82984-6 |
| spellingShingle | Mst. Kusum Kaly Md Ekhtiar Rahman Md. Sohel Rana Uzzal Kumar Acharjee Khondokar Nasirujjaman Genotoxic effects of NDMA-contaminated ranitidine on Allium cepa cells and unveiling carcinogenic mechanisms via DFT and molecular dynamics simulation study Scientific Reports |
| title | Genotoxic effects of NDMA-contaminated ranitidine on Allium cepa cells and unveiling carcinogenic mechanisms via DFT and molecular dynamics simulation study |
| title_full | Genotoxic effects of NDMA-contaminated ranitidine on Allium cepa cells and unveiling carcinogenic mechanisms via DFT and molecular dynamics simulation study |
| title_fullStr | Genotoxic effects of NDMA-contaminated ranitidine on Allium cepa cells and unveiling carcinogenic mechanisms via DFT and molecular dynamics simulation study |
| title_full_unstemmed | Genotoxic effects of NDMA-contaminated ranitidine on Allium cepa cells and unveiling carcinogenic mechanisms via DFT and molecular dynamics simulation study |
| title_short | Genotoxic effects of NDMA-contaminated ranitidine on Allium cepa cells and unveiling carcinogenic mechanisms via DFT and molecular dynamics simulation study |
| title_sort | genotoxic effects of ndma contaminated ranitidine on allium cepa cells and unveiling carcinogenic mechanisms via dft and molecular dynamics simulation study |
| url | https://doi.org/10.1038/s41598-024-82984-6 |
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