丁螺环酮、西替利嗪、奥氮平对人外周血淋巴细胞的体外毒性分析。

IF 3.2 Q2 Pharmacology, Toxicology and Pharmaceutics

Current clinical pharmacology Pub Date : 2018-01-01 DOI:10.2174/1574884713666180516112920

Ahmad Salimi, Mosleh Razian, Jalal Pourahmad

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引用次数: 9

摘要

背景:本研究旨在探讨西替利嗪、奥氮平、丁螺环酮等常见含哌嗪环的药物对人淋巴细胞的细胞毒性机制。方法:测定淋巴细胞活力、活性氧(ROS)形成、线粒体膜电位(MMP)崩溃、溶酶体完整性、谷胱甘肽含量和脂质过氧化。结果:丁螺环酮和西替利嗪对人淋巴细胞的毒性大于奥氮平，IC50值为200µg/ml。丁螺环酮和西替利嗪浓度(4、20、40µg/ml)处理淋巴细胞后，观察到明显的ROS形成、MMP崩溃、脂质过氧化、溶酶体损伤和谷胱甘肽二硫(GSSG)升高。结论:人体淋巴细胞暴露于丁螺环酮和西替利嗪后，可引起氧化应激和细胞器损伤。我们的研究表明，使用抗氧化剂、线粒体和溶酶体保护剂可以保护血液淋巴细胞免受这些高度消耗的药物可能产生的副作用。

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Analysis of Toxicity Effects of Buspirone, Cetirizine and Olanzapine on Human Blood Lymphocytes: in Vitro Model.

Background: The current study investigates the cytotoxicity mechanism of common drugs with piperazine ring such as cetirizine, olanzapine and buspirone on human lymphocytes.

Methods: The viability of lymphocytes, reactive oxygen species (ROS) formation, mitochondrial membrane potential (MMP) collapse, lysosomal integrity, content of glutathione and lipid peroxidation was determined.

Results: Buspirone and cetirizine showed more toxicity than olanzapine on human lymphocytes with an IC50 value of 200 µg/ml, after 6 h of incubation. Significant ROS formation, MMP collapse, lipid peroxidation, lysosomal damage and elevation of glutathione disulfide (GSSG) were observed in treated lymphocytes concentrations (4, 20, 40 µg/ml) of buspirone and cetirizine.

Conclusion: Our results show the exposure of human lymphocytes with buspirone and cetirizine, which usually happens during the poisoning, triggers oxidative stress and organelle damages. Our study suggests that using antioxidants, mitochondrial and lysosomal protective agents can protect blood lymphocytes, from probable side effects of these highly consumed medications.

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来源期刊

Current clinical pharmacology PHARMACOLOGY & PHARMACY-

CiteScore

3.60

自引率

0.00%

发文量

期刊介绍： Current Clinical Pharmacology publishes frontier reviews on all the latest advances in clinical pharmacology. The journal"s aim is to publish the highest quality review articles in the field. Topics covered include: pharmacokinetics; therapeutic trials; adverse drug reactions; drug interactions; drug metabolism; pharmacoepidemiology; and drug development. The journal is essential reading for all researchers in clinical pharmacology.