The Protective Effect of Cilostazol in Genotoxicity Induced by Methotrexate in Human Cultured Lymphocytes

Background: 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. Objective: To evaluate the potential protective effect of cilostazol on methotrexate genotoxicity. Methods: The genotoxic effect of methotrexate by measuring the frequency of chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) in human cultured lymphocytes was studied. Results: 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). Conclusion: Methotrexate is genotoxic, and cilostazol could prevent the methotrexate-induced chromosomal damage with no modulation of methotrexate-induced cytotoxicity.