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

(E-pub Ahead of Print)

Author(s): Abeer M. Rababa’h*, Samah A. Hussein, Omar F. Khabour, Karem H. Alzoubi.

Journal Name: Current Molecular Pharmacology

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Abstract:

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.

Keywords: Methotrexate, Cilostazol, Genotoxicity, Chromosomal aberrations, Sister chromatid exchanges, Proliferative index

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(E-pub Ahead of Print)
DOI: 10.2174/1874467212666191023120118
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