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奥氮平作为一种抗精神病药物对电离辐射诱导的人淋巴细胞遗传毒性和细胞凋亡的防护作用。

Radioprotective effect of olanzapine as an anti-psychotic drug against genotoxicity and apoptosis induced by ionizing radiation on human lymphocytes.

机构信息

Department of Radiopharmacy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.

Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran.

出版信息

Mol Biol Rep. 2019 Dec;46(6):5909-5917. doi: 10.1007/s11033-019-05024-x. Epub 2019 Aug 12.

Abstract

Olanzapine (OLA), is prescribed as an anti-psychotic medicine in schizophrenia patients. In this study, the protective effect of OLA against genotoxicity and apoptosis induced by ionizing radiation in human healthy lymphocytes was evaluated. At first, the antioxidant activities of OLA were assayed by two different methods as free radical scavenging with DPPH (2,2-diphenyl-1-picryl-hydrazyl) and ferric reducing power methods. In in vitro experiment, human blood samples were treated with OLA at various concentrations (0.25-20 μM) for 3 h and then were exposed to X-ray at a dose of 150 cGy. The genotoxicity was assessed in binucleated human lymphocytes with micronuclei assay. The apoptotic lymphocytes were assessed by flow cytometry in OLA treated and/or irradiated lymphocytes. OLA exhibited free radical scavenging and reducing power activities more than ascorbic acid. The results showed that the lymphocytes treated with OLA and later exposed to IR presented lower frequencies of micronuclei and apoptosis compared to the control sample which was irradiated and not treated to OLA. The maximum radioprotection was observed at 20 μM of OLA with 83% of efficacy. The present study suggested the protective role for OLA in protection radiation-induced genetic damage and apoptosis induced by ionizing irradiation in human normal cells.

摘要

奥氮平(OLA)被规定用于精神分裂症患者的抗精神病药物。在这项研究中,评估了 OLA 对人健康淋巴细胞中致突变性和由电离辐射诱导的细胞凋亡的保护作用。首先,通过两种不同的方法测定了 OLA 的抗氧化活性,即用 DPPH(2,2-二苯基-1-苦基肼)进行自由基清除和铁还原能力方法。在体外实验中,用人血样在不同浓度(0.25-20μM)下处理 3 小时,然后用 150cGy 的 X 射线照射。用微核试验评估双核人淋巴细胞的致突变性。通过流式细胞术评估 OLA 处理和/或照射的淋巴细胞中的凋亡淋巴细胞。OLA 表现出比抗坏血酸更强的自由基清除和还原能力活性。结果表明,与未用 OLA 照射和处理的对照样品相比,用 OLA 处理然后暴露于 IR 的淋巴细胞中的微核和凋亡频率较低。在 20μM 的 OLA 时观察到最大的放射防护效果,功效为 83%。本研究表明,OLA 在保护人正常细胞中由电离辐射诱导的遗传损伤和细胞凋亡方面具有保护作用。

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