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

Abstract

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.