西洛他唑对奈达铂致人淋巴细胞遗传毒性的保护作用

Q1 Environmental Science

Toxicology Reports Pub Date : 2025-01-25 DOI:10.1016/j.toxrep.2025.101928

Karem H. Alzoubi , Abeer M. Rababa’h , Omar F. Khabour , Fian Nuseir

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引用次数: 0

摘要

奈达铂在治疗多种恶性肿瘤方面已显示出显著的疗效。然而，奈达铂的施用与正常细胞内DNA损伤的诱导有关。西洛他唑是一种具有抗氧化机制的磷酸二酯酶III抑制剂，可以保护细胞免受遗传毒性。我们的目的是评估奈达铂对培养的人淋巴细胞的遗传毒性作用以及西洛他唑对奈达铂诱导的染色体损伤的潜在保护作用。方法通过观察体外培养的人淋巴细胞姐妹染色单体交换（ses）的频率，研究奈达铂的基因毒性作用。有丝分裂指数和增殖指数（分别为MI和PI）用于评估奈达铂的细胞毒性作用。结果与对照组和西洛他唑处理的细胞相比，奈达铂显著增加了sce的发生频率。西洛他唑预处理细胞后，奈达铂诱导的染色体损伤明显减轻（P <； 0.0001）。与对照组相比，单独使用西洛他唑也降低了ses， MI和PI的频率。与对照组相比，奈达铂诱导心肌梗死和PI显著降低。西洛他唑预处理可以部分减弱奈达铂引起的心肌梗死，但不能减弱PI。结论西洛他唑可改善奈达铂对培养人淋巴细胞的遗传毒性。

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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 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.