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西洛他唑的基因保护作用可减轻卡马西平在人培养血淋巴细胞中诱导的基因毒性。

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

作者信息

Al Momany Enaam M, Rababa'h Abeer M, Alzoubi Karem H, Khabour Omar F

机构信息

Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmaceutical Sciences, The Hashemite University, P.O. box 330127, Zarqa 13133, Jordan.

Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.

出版信息

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

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.

摘要

背景

卡马西平是使用最广泛的抗癫痫药物之一。已证明卡马西平对细胞有毒性。西洛他唑是一种抗血小板药物,具有抗氧化、抗增殖、抗炎和抗肿瘤作用。

目的

本研究旨在探讨卡马西平和西洛他唑对人培养血液淋巴细胞是否具有遗传毒性和/或细胞毒性作用,以及两种药物联合使用对此类作用的影响。

方法

采用姐妹染色单体交换(SCE)试验检测遗传毒性,通过细胞动力学试验(有丝分裂和增殖指数)评估细胞毒性。

结果

研究结果显示,卡马西平显著增加了SCEs(p<0.01),而西洛他唑显著降低了其频率(p<0.01)。此外,两种药物联合使用时SCEs的频率与对照组相似(p>0.05)。卡马西平增加了细胞增殖指数(p<0.01),而西洛他唑降低了该指数(p<0.01)。两种药物联合使用时,增殖指数恢复到对照水平。

结论

我们认为西洛他唑有可能保护人淋巴细胞免受卡马西平诱导的毒性作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b3c2/11626827/6b819dff95b9/gr1.jpg

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