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.