Cilostazol protective effect on nedaplatin-induced genotoxicity in cultured human lymphocytes
Background: Nedaplatin has demonstrated remarkable efficacy in combating various malignancies. However, the administration of nedaplatin has been associated with the induction of DNA damage within normal cells. Cilostazol is a phosphodiesterase III inhibitor with an antioxidant mechanism that could...
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Elsevier
2025-06-01
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| Series: | Toxicology Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214750025000460 |
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| author | Karem H. Alzoubi Abeer M. Rababa’h Omar F. Khabour Fian Nuseir |
| author_facet | Karem H. Alzoubi Abeer M. Rababa’h Omar F. Khabour Fian Nuseir |
| author_sort | Karem H. Alzoubi |
| collection | DOAJ |
| description | Background: Nedaplatin has demonstrated remarkable efficacy in combating various malignancies. However, the administration of nedaplatin has been associated with the induction of DNA damage within normal cells. Cilostazol is a phosphodiesterase III inhibitor with an antioxidant mechanism that could protect cells from genotoxicity. We aimed to evaluate the genotoxic effect of nedaplatin on cultured human lymphocytes and the potential protective effect of cilostazol on chromosomal damage induced by nedaplatin. Methods: The proposed nedaplatin’s genotoxic effect was studied in vitro by evaluating the frequencies of sister chromatid exchanges (SCEs) in human cultured lymphocytes. Both the mitotic and proliferative indices (MI and PI, respectively) were used to assess the cytotoxic effects of nedaplatin. Results: Nedaplatin significantly increased the frequency of SCEs compared to control and cilostazol-treated cells. The chromosomal injury induced by nedaplatin was significantly reduced by pretreatment of cells with cilostazol (P < 0.0001). Treating with cilostazol alone also reduced the frequency of SCEs, MI, and PI compared to the control group. Nedaplatin induced significant decreases in the MI and PI compared to the control group. Pretreatment with cilostazol partially debilitated the nedaplatin-induced changes in MI but not PI. Conclusion: Cilostazol ameliorated the genotoxicity of nedaplatin in cultured human lymphocytes. |
| format | Article |
| id | doaj-art-01a5e48399df40c9af6da2332bb0e481 |
| institution | Kabale University |
| issn | 2214-7500 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
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| series | Toxicology Reports |
| spelling | doaj-art-01a5e48399df40c9af6da2332bb0e4812025-01-28T04:14:39ZengElsevierToxicology Reports2214-75002025-06-0114101928Cilostazol protective effect on nedaplatin-induced genotoxicity in cultured human lymphocytesKarem H. Alzoubi0Abeer M. Rababa’h1Omar F. Khabour2Fian Nuseir3Department of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, The University of Sharjah, Sharjah 27272, United Arab Emirates; Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; Correspondence to: Department of Clinical Pharmacy, Jordan University of Science and Technology, PO Box 3030, Irbid 22110, Jordan.Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; Division of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 200 First St SW, Rochester, MN 55902, USADepartment of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Irbid, JordanDepartment of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Irbid, JordanBackground: Nedaplatin has demonstrated remarkable efficacy in combating various malignancies. However, the administration of nedaplatin has been associated with the induction of DNA damage within normal cells. Cilostazol is a phosphodiesterase III inhibitor with an antioxidant mechanism that could protect cells from genotoxicity. We aimed to evaluate the genotoxic effect of nedaplatin on cultured human lymphocytes and the potential protective effect of cilostazol on chromosomal damage induced by nedaplatin. Methods: The proposed nedaplatin’s genotoxic effect was studied in vitro by evaluating the frequencies of sister chromatid exchanges (SCEs) in human cultured lymphocytes. Both the mitotic and proliferative indices (MI and PI, respectively) were used to assess the cytotoxic effects of nedaplatin. Results: Nedaplatin significantly increased the frequency of SCEs compared to control and cilostazol-treated cells. The chromosomal injury induced by nedaplatin was significantly reduced by pretreatment of cells with cilostazol (P < 0.0001). Treating with cilostazol alone also reduced the frequency of SCEs, MI, and PI compared to the control group. Nedaplatin induced significant decreases in the MI and PI compared to the control group. Pretreatment with cilostazol partially debilitated the nedaplatin-induced changes in MI but not PI. Conclusion: Cilostazol ameliorated the genotoxicity of nedaplatin in cultured human lymphocytes.http://www.sciencedirect.com/science/article/pii/S2214750025000460NedaplatinCilostazolMitotic indexHuman cultured lymphocytesSister chromatid exchangesGenotoxicity |
| spellingShingle | Karem H. Alzoubi Abeer M. Rababa’h Omar F. Khabour Fian Nuseir Cilostazol protective effect on nedaplatin-induced genotoxicity in cultured human lymphocytes Toxicology Reports Nedaplatin Cilostazol Mitotic index Human cultured lymphocytes Sister chromatid exchanges Genotoxicity |
| title | Cilostazol protective effect on nedaplatin-induced genotoxicity in cultured human lymphocytes |
| title_full | Cilostazol protective effect on nedaplatin-induced genotoxicity in cultured human lymphocytes |
| title_fullStr | Cilostazol protective effect on nedaplatin-induced genotoxicity in cultured human lymphocytes |
| title_full_unstemmed | Cilostazol protective effect on nedaplatin-induced genotoxicity in cultured human lymphocytes |
| title_short | Cilostazol protective effect on nedaplatin-induced genotoxicity in cultured human lymphocytes |
| title_sort | cilostazol protective effect on nedaplatin induced genotoxicity in cultured human lymphocytes |
| topic | Nedaplatin Cilostazol Mitotic index Human cultured lymphocytes Sister chromatid exchanges Genotoxicity |
| url | http://www.sciencedirect.com/science/article/pii/S2214750025000460 |
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