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在人淋巴细胞培养物中研究精神药物的体内细胞遗传学效应。

The investigation of the in vivo cytogenetic effects of psychotropic drugs in human lymphocyte cultures.

机构信息

Department of Applied Biological Sciences, Jordan University of Science and Technology, Irbid, Jordan/Department of Biotechnology and Genetic Engineering, Jordan University of Science and Technology, Irbid, Jordan.

Department of Applied Biological Sciences, Jordan University of Science and Technology, Irbid, Jordan.

出版信息

Pak J Pharm Sci. 2020 Jul;33(4):1503-1510.

PMID:33583780
Abstract

The connection of nearly all current antipsychotic drugs to their in vivo cytogenetic activity has not been yet fully investigated. Fluvoxamine, Valproic acid (VA) and Haloperidol (HLP) are three universally common consumed psychotic drugs whereas used to treat several psychiatric disorders. This study aims to investigate the cytogenetic effects of these three psychotropic drugs by evaluating the frequency of Sister Chromatid Exchanges (SCEs) and the Proliferation Rate Index (PRI) in cultured lymphocytes. Fifteen patients with psychiatric disorders (i.e. depression, bipolar and schizophrenia) consisting of smokers and non-smokers were included. Estimation of SCEs was used as a sensitive biomarker of the potential cytotoxicity, while PRI was used as a valuable marker of cytostatic activity. A significant increase of SCEs in the cultured lymphocyte of the smoker controls (P= 0.013) was found in compared to the non-smoker controls. This study found that there is no difference in the average of SCEs values in lymphocytes isolated from the smoker and non-smoker patients treated with Fluvoxamine, Valproic acid and Haloperidol (P> 0.05). A significant difference of PRI (P= 0.036) in the lymphocytes of smoker controls compared to those of the non-smoker controls were detected. This study also found a significant difference with respect to PRI between the three patient groups (P= 0.017). These results illustrated that treatment (monotherapy) of psychiatric patients with Fluvoxamine, Valproic acid, and Haloperidol exerts a significant cytostatic but not cytotoxic effect on their lymphocytes whereas these effects are intensified by smoking.

摘要

目前,几乎所有抗精神病药物与体内细胞遗传学活性的关系尚未得到充分研究。氟伏沙明、丙戊酸(VA)和氟哌啶醇(HLP)是三种普遍使用的精神药物,用于治疗多种精神疾病。本研究旨在通过评估培养淋巴细胞中的姐妹染色单体交换(SCEs)和增殖率指数(PRI)来研究这三种精神药物的细胞遗传学效应。共纳入 15 名患有精神疾病(抑郁症、双相情感障碍和精神分裂症)的吸烟者和非吸烟者患者。SCEs 的估计被用作潜在细胞毒性的敏感生物标志物,而 PRI 被用作细胞抑制活性的有价值标志物。与非吸烟者对照相比,吸烟者对照培养的淋巴细胞中的 SCEs 显著增加(P=0.013)。本研究发现,吸烟者和非吸烟者患者的淋巴细胞中 SCEs 值的平均值无差异,这些患者接受氟伏沙明、丙戊酸和氟哌啶醇治疗(P>0.05)。与非吸烟者对照相比,吸烟者对照的淋巴细胞中 PRI 存在显著差异(P=0.036)。本研究还发现,三组患者之间的 PRI 存在显著差异(P=0.017)。这些结果表明,精神科患者用氟伏沙明、丙戊酸和氟哌啶醇进行治疗(单药治疗)对其淋巴细胞产生显著的细胞抑制作用,但无细胞毒性作用,而吸烟会加剧这些作用。

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