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氟哌啶醇对系统性红斑狼疮和类风湿关节炎患者T淋巴细胞的细胞遗传学影响:一项体外研究

Haloperidol's Cytogenetic Effect on T Lymphocytes of Systemic Lupus Erythematosus and Rheumatoid Arthritis Patients: An In Vitro Study.

作者信息

Demirtzoglou Georgios, Chrysoglou Sofia-Ifigeneia, Iakovidou-Kritsi Zafeiroula, Lambropoulos Alexandros, Garyfallos Alexandros

机构信息

1st Laboratory of Medical Biology and Genetics, School of Medicine, Faculty of Health Sciences (FHS) of Aristotle University of Thessaloniki, Thessaloniki, GRC.

Department of Rheumatology, 251 General Airforce Hospital, Athens, GRC.

出版信息

Cureus. 2023 Jul 21;15(7):e42283. doi: 10.7759/cureus.42283. eCollection 2023 Jul.

Abstract

OBJECTIVES

Investigating haloperidol's cytogenetic behavior in cultured human T lymphocytes of patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

METHODS

Four haloperidol solutions were added in cultures of peripheral blood lymphocytes of healthy individuals, SLE, and RA patients. After 72 hours of incubation, the cultured lymphocytes were plated on glass slides, and stained with the fluorescence plus Giemsa method, and sister chromatid exchanges (SCEs), proliferation rate index (PRI), and mitotic index (MI) were measured with the optical microscope.

RESULTS

Result analysis revealed: (a) a statistically significant (p=0.001) dose-dependent increase of SCEs in SLE patients compared to healthy individuals; (b) a statistically significant (p=0.001) dose-dependent decrease of SCEs in RA patients for haloperidol concentrations 5, 10μg/mL; (c) a statistically significant (p=0.001) dose-dependent increase of SCEs in RA patients for haloperidol concentrations 20, 100μg/mL; and (d) a statistically significant (p=0.001) dose-dependent reduction of PRI and MI in both patient groups compared to healthy individuals. Furthermore, a correlation was observed between (a) SCE and PRI index variations, (b) MI and SCE index variations, and (c) PRI and MI index variations.

CONCLUSIONS

Haloperidol affects T lymphocytes from SLE and RA patients by modifying DNA replication procedures, DNA damage response, and ferroptosis. Considering the wide use of haloperidol in neuropsychiatric symptoms of SLE and RA patients, further studies with more immune cell subsets are needed to evaluate its effects on human genetic material.

摘要

目的

研究氟哌啶醇在系统性红斑狼疮(SLE)和类风湿关节炎(RA)患者培养的人T淋巴细胞中的细胞遗传学行为。

方法

将四种氟哌啶醇溶液添加到健康个体、SLE和RA患者的外周血淋巴细胞培养物中。孵育72小时后,将培养的淋巴细胞铺在载玻片上,用荧光加吉姆萨法染色,并用光学显微镜测量姐妹染色单体交换(SCE)、增殖率指数(PRI)和有丝分裂指数(MI)。

结果

结果分析显示:(a)与健康个体相比,SLE患者的SCEs呈剂量依赖性增加,差异有统计学意义(p = 0.001);(b)对于氟哌啶醇浓度为5、10μg/mL的RA患者,SCEs呈剂量依赖性降低,差异有统计学意义(p = 0.001);(c)对于氟哌啶醇浓度为20、100μg/mL的RA患者,SCEs呈剂量依赖性增加,差异有统计学意义(p = 0.001);(d)与健康个体相比,两组患者的PRI和MI均呈剂量依赖性降低,差异有统计学意义(p = 0.001)。此外,观察到(a)SCE与PRI指数变化之间、(b)MI与SCE指数变化之间以及(c)PRI与MI指数变化之间存在相关性。

结论

氟哌啶醇通过改变DNA复制程序、DNA损伤反应和铁死亡来影响SLE和RA患者的T淋巴细胞。鉴于氟哌啶醇在SLE和RA患者神经精神症状中的广泛应用,需要对更多免疫细胞亚群进行进一步研究,以评估其对人类遗传物质的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19c6/10440589/de73b515e62d/cureus-0015-00000042283-i01.jpg

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