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 strong antioxidant drug.
Objectives: In this study, we aimed to evaluate the potential protective effect of cilostazol on methotrexate genotoxicity. Methods: we studied the genotoxic effect of methotrexate by measuring the frequency of chromosomal aberrations (CAs) and sister chromatid exchanges (SCEs) in human cultured lymphocytes. .
Results: Results showed that 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 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 anti-proliferative effect (P < 0.01).
Conclusion: We concluded that methotrexate is genotoxic, and cilostazol could prevent the methotrexate-induced chromosomal damage with no modulation of methotrexate-induced cytotoxicity.