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. 2024 Nov 17:13:101814.
doi: 10.1016/j.toxrep.2024.101814. eCollection 2024 Dec.

Cilostazol geno-protective effects mitigate carbamazepine-induced genotoxicity in human cultured blood lymphocytes

Enaam M Al Momany  1 , Abeer M Rababa'h  2 , Karem H Alzoubi  3   4 , Omar F Khabour  5
Affiliations

Cilostazol geno-protective effects mitigate carbamazepine-induced genotoxicity in human cultured blood lymphocytes

Enaam M Al Momany et al. Toxicol Rep. .

Abstract

Background: Carbamazepine is one of the most widely used antiepileptic drugs. Carbamazepine has been shown to be toxic to cells. Cilostazol, an antiplatelet agent, has known antioxidant, antiproliferative, anti-inflammatory, and anti-tumor effects.

Objective: This study aimed to explore whether carbamazepine and cilostazol exert genotoxic and/or cytotoxic effects in human cultured blood lymphocytes and the impact of combining both drugs on such effects.

Methods: Genotoxicity was examined using sister chromatid exchange (SCE) assay, while cytotoxicity was evaluated by cell kinetic assays (mitotic and proliferative indices).

Results: Study findings have revealed that carbamazepine markedly increased SCEs (p<0.01), while cilostazol significantly decreased their frequencies (p<0.01). In addition, the frequency of SCEs of the combination of both drugs was similar to that of the control group (p>0.05). Carbamazepine increased the cell proliferative index (p<0.01) while cilostazol decreased it (p<0.01). The proliferative index was normalized to the control level when both drugs were combined.

Conclusion: We suggest that cilostazol has the potential to protect human lymphocytes from carbamazepine-induced toxic effects.

Keywords: Carbamazepine; Cell kinetic assays; Cilostazol; Cytotoxic; Genotoxic; Sister chromatid exchange.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Quantitative comparison of the means of sister chromatid exchange (SCE) frequency in human cultured blood lymphocytes upon treatment with cilostazol and/or carbamazepine. ANOVA and Tukey's post hoc test were used for statistical analysis. *: Denotes the statistical significance of each pairwise comparisons of cilostazol with the control (p<0.0001), carbamazepine (p<0.0001), and carbamazepine+ cilostazol (p<0.0001) groups. $: Denotes the statistical significance of each pairwise comparisons of carbamazepine with the control (p<0.0001), cilostazol (p<0.0001), and carbamazepine+ cilostazol (p<0.001) groups.
Fig. 2
Fig. 2
Quantitative comparison of the ratio means of mitotic index (MI) in human cultured blood lymphocytes following treatment with cilostazol, carbamazepine or both. Error bars indicate standard deviation (n = 5–10). *: Denotes the statistical significance of each pairwise comparisons of cilostazol with the control (p<0.05), and carbamazepine (p<0.05) groups.
Fig. 3
Fig. 3
Quantitative comparison of the means of cell proliferative index (PI) in human cultured blood lymphocytes upon treatment with cilostazol and/or carbamazepine. Error bars indicate standard deviation (n = 5–10). *: Denotes the statistical significance of each pairwise comparisons of cilostazol with the control (p<0.001), carbamazepine (p<0.0001), and carbamazepine+ cilostazol (p>0.05) groups. $: Denotes the statistical significance of each pairwise comparisons of carbamazepine with the control (p<0.001), cilostazol (p<0.0001), and carbamazepine+ cilostazol (p<0.0001) groups.
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