Mitochondrial Transplantation Attenuates Toxicity in Human Lymphocytes Caused by Clozapine and Risperidone

IF 1.4 Q4 PHARMACOLOGY & PHARMACY
Abdollah Arjmand, Elaheh Azizi Javan, J. Shahraki, Rozhin Shaboustani, Enayatollah Seydi, J. Pourahmad
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Abstract

Background: Clozapine (CLZ) and risperidone (RIS) are drugs that have the ability to disrupt mitochondrial function. Also, these drugs increase the level of free radicals. Mitochondrial dysfunction plays a role in the etiology of various diseases. Replacement and treatment of defective mitochondria with healthy mitochondria have been considered. Mitochondrial therapy (mitotherapy) or exogenous mitochondria transplantation is a method that can be used to replace dysfunctional mitochondria with healthy mitochondria. This method can help in the treatment of diseases related to mitochondria. Methods: In this study, we investigated the transplantation effect of isolated lymphocyte mitochondria on the toxicity induced by CLZ and RIS on human blood lymphocytes. Lymphocytes were isolated using the Ficoll standard method. Mitochondria of human lymphocytes were used for mitotherapy. This study was conducted in 6 groups. After treatment, the level of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), reduced glutathione (GSH) content, oxidized glutathione (GSSG) content, and adenosine triphosphate (ATP) content were evaluated. Results: Our data showed that CLZ (70 µm) and RIS (24 nM) caused cytotoxicity on human blood lymphocytes which are associated with ROS generation, collapse in MMP, decrease in GSH content, increase in GSSG content and change in ATP content. Mitochondria transplantation results showed that adding mitochondria of lymphocytes could protect the lymphocytes against the toxicity effects caused by CLZ and RIS. Furthermore, the results showed that pre-incubation with cytochalasin D considerably reserved the protective effects of mitotherapy in the human lymphocytes. Conclusion: We proposed that mitochondria transplantation or mitotherapy-affected blood lymphocytes with exogenous mitochondria could be used to treat CLZ and RIS-induced toxicity.
线粒体移植可减轻氯氮平和利培酮对人类淋巴细胞的毒性
背景:氯氮平(CLZ)和利培酮(RIS)是能够破坏线粒体功能的药物。此外,这些药物还会增加自由基的水平。线粒体功能障碍是多种疾病的病因之一。人们考虑用健康的线粒体替代和治疗有缺陷的线粒体。线粒体疗法(线粒体疗法)或外源线粒体移植是一种用健康线粒体替代功能障碍线粒体的方法。这种方法有助于治疗与线粒体有关的疾病。方法:本研究探讨了分离的淋巴细胞线粒体移植对 CLZ 和 RIS 诱导的人类血液淋巴细胞毒性的影响。采用 Ficoll 标准方法分离淋巴细胞。人淋巴细胞线粒体用于有丝分裂疗法。这项研究分 6 组进行。治疗后,评估了活性氧(ROS)水平、线粒体膜电位(MMP)、还原型谷胱甘肽(GSH)含量、氧化型谷胱甘肽(GSSG)含量和三磷酸腺苷(ATP)含量。结果显示我们的数据显示,CLZ(70 µm)和 RIS(24 nM)对人血淋巴细胞产生细胞毒性,这与 ROS 生成、MMP 崩溃、GSH 含量降低、GSSG 含量增加和 ATP 含量变化有关。线粒体移植结果表明,添加淋巴细胞线粒体可以保护淋巴细胞免受 CLZ 和 RIS 的毒性影响。此外,研究结果表明,用细胞松弛素 D 预孵育人淋巴细胞可大大降低有丝分裂疗法对淋巴细胞的保护作用。结论我们提出,线粒体移植或用外源性线粒体移植受有丝分裂疗法影响的血液淋巴细胞可用于治疗 CLZ 和 RIS 引起的毒性。
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来源期刊
Pharmaceutical Sciences
Pharmaceutical Sciences PHARMACOLOGY & PHARMACY-
CiteScore
2.60
自引率
5.90%
发文量
38
审稿时长
4 weeks
期刊介绍: Pharmaceutical Sciences provides a forum for the publication of original research articles, reviews, short communications, and editorials (by invitation only) in all areas of pharmaceutical sciences, including these topics: Clinical Pharmacy Medicinal and Pharmaceutical Chemistry Pharmaceutical Analysis Pharmaceutics Pharmacognosy Pharmacology and Toxicology Pharmaceutical Biotechnology Pharmaceutical Nanotechnology Pharmacoeconomy Radiopharmacy Water, Food, Drug and Cosmetic Control.
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