Department of Clinical Pharmacy, College of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.
Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Irbid, Jordan.
Curr Mol Pharmacol. 2020;13(2):137-143. doi: 10.2174/1874467212666191023120118.
Methotrexate is an antagonist of folic acid that has been shown to be genotoxic to healthy body cells via induction of oxidative stress. Cilostazol is a phosphodiesterase III inhibitor and a potent antioxidant drug.
To evaluate the potential protective effect of cilostazol on methotrexate genotoxicity.
The genotoxic effect of methotrexate by measuring the frequency of chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) in human cultured lymphocytes was studied.
Methotrexate significantly increased the frequency of CAs and SCEs (p < 0.0001) as compared to control cultures. This chromosomal damage induced by methotrexate was considerably decreased by pretreatment of the cells with cilostazol (P < 0.01). Moreover, the results showed that methotrexate resulted in a notable reduction (P < 0.01) in cells kinetic parameters, the mitotic index (MI) and the proliferative index (PI). Similarly, cilostazol significantly reduced the mitotic index, which could be related to the anti-proliferative effect (P < 0.01).
Methotrexate is genotoxic, and cilostazol could prevent the methotrexate-induced chromosomal damage with no modulation of methotrexate-induced cytotoxicity.
甲氨蝶呤是一种叶酸拮抗剂，通过诱导氧化应激已被证明对健康体细胞具有遗传毒性。西洛他唑是一种磷酸二酯酶 III 抑制剂和有效的抗氧化药物。
评估西洛他唑对甲氨蝶呤遗传毒性的潜在保护作用。
通过测量人培养淋巴细胞中的染色体畸变（CA）和姐妹染色单体交换（SCE）频率来研究甲氨蝶呤的遗传毒性作用。
与对照组相比，甲氨蝶呤显著增加了 CA 和 SCE 的频率（p<0.0001）。甲氨蝶呤诱导的这种染色体损伤可通过西洛他唑预处理细胞显著减少（p<0.01）。此外，结果表明，甲氨蝶呤导致细胞动力学参数显著降低，有丝分裂指数（MI）和增殖指数（PI）显著降低（p<0.01）。同样，西洛他唑显著降低了有丝分裂指数，这可能与抗增殖作用有关（p<0.01）。
甲氨蝶呤具有遗传毒性，西洛他唑可预防甲氨蝶呤诱导的染色体损伤，而不调节甲氨蝶呤诱导的细胞毒性。
