Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Students Research Committee, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Cancer Research Center, Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Biomed Pharmacother. 2018 Dec;108:1244-1252. doi: 10.1016/j.biopha.2018.09.106. Epub 2018 Oct 2.
The aim of this study was to investigate the neurotoxic effects of FeO magnetic- CurNPs on isolated schizophrenia mitochondria of rats as an in vivo model.
We designed CMN loaded superparamagnetic iron oxide nanoparticles (SPIONs) (FeO magnetic- CurNPs) to achieve an enhanced therapeutic effect. The physicochemical properties of FeO magnetic- CurNPs were characterized using X-ray diffraction (XRD), and dynamic laser light scattering (DLS) and zeta potential. Further, to prove FeO magnetic- CurNPs results in superior therapeutic effects, and also, the mitochondrial membrane potential collapse, mitochondrial complex II activity, reactive oxygen species generation, ATP level, cytochrome c release and histopathology of cerebellums were determined in brains of schizophrenic rats.
We showed that effective treatment with CMN reduced or prevented FeO magnetic-induced oxidative stress and mitochondrial dysfunction in the rat brain probably, as well as mitochondrial complex II activity, MMP, and ATP level were remarkably reduced in the cerebellum mitochondria of treated group toward control (p < 0.05). Therewith, ROS generation, and cytochrome c release were notably (p < 0.05) increased in the cerebellum mitochondria of treated group compared with control group.
Taken together, FeO magnetic- CurNPs exhibits potent antineurotoxicity activity in cerebellums of schizophrenic rats. This approach can be extended to preclinical and clinical use and may have importance in schizophernia treatment in the future. To our knowledge this is the first report that provides the FeO magnetic- CurNPs could enhance the neuroprotective effects of CMN in the Schizophrenia.
本研究旨在探讨 FeO 磁性- CurNPs 对大鼠分离性精神分裂症线粒体的神经毒性作用，作为体内模型。
我们设计了载有 CMN 的超顺磁性氧化铁纳米粒子（SPIONs）（FeO 磁性-CurNPs）以达到增强治疗效果。使用 X 射线衍射（XRD）、动态激光光散射（DLS）和zeta 电位对 FeO 磁性-CurNPs 的理化性质进行了表征。此外，为了证明 FeO 磁性-CurNPs 具有更好的治疗效果，还测定了精神分裂症大鼠脑内线粒体膜电位崩溃、线粒体复合物 II 活性、活性氧生成、ATP 水平、细胞色素 c 释放和小脑组织病理学的变化。
我们表明，CMN 的有效治疗减轻或预防了 FeO 磁性诱导的氧化应激和大鼠脑内线粒体功能障碍，可能是由于治疗组小脑线粒体中复合物 II 活性、MMP 和 ATP 水平明显降低（p < 0.05）。此外，与对照组相比，治疗组小脑线粒体中 ROS 生成和细胞色素 c 释放显著增加（p < 0.05）。
综上所述，FeO 磁性-CurNPs 对精神分裂症大鼠小脑具有明显的抗神经毒性作用。这种方法可以扩展到临床前和临床应用，在未来的精神分裂症治疗中可能具有重要意义。据我们所知，这是首次报道 FeO 磁性-CurNPs 可以增强 CMN 在精神分裂症中的神经保护作用。
