Maghsoudi Amirhossein, Fakharzadeh Saideh, Hafizi Maryam, Abbasi Maryam, Kohram Fatemeh, Sardab Shima, Tahzibi Abbas, Kalanaky Somayeh, Nazaran Mohammad Hassan
Department of Research and Development, Sodour Ahrar Shargh Company, Tehran, Iran.
Apoptosis. 2015 Mar;20(3):298-309. doi: 10.1007/s10495-014-1069-x.
Parkinson's disease (PD) is the world's second most common dementia, which the drugs available for its treatment have not had effects beyond slowing the disease process. Recently nanotechnology has induced the chance for designing and manufacturing new medicines for neurodegenerative disease. It is demonstrated that by tuning the size of a nanoparticle, the physiological effect of the nanoparticle can be controlled. Using novel nanochelating technology, three nano complexes: Pas (150 nm), Paf (100 nm) and Pac (40 nm) were designed and in the present study their neuroprotective effects were evaluated in PC12 cells treated with 1-methyl-4-phenyl-pyridine ion (MPP (+)). PC12 cells were pre-treated with the Pas, Paf or Pac nano complexes, then they were subjected to 10 μM MPP (+). Subsequently, cell viability, intracellular free Calcium and reactive oxygen species (ROS) levels, mitochondrial membrane potential, catalase (CAT) and superoxide dismutase (SOD) activity, Glutathione (GSH) and malondialdehyde (MDA) levels and Caspase 3 expression were evaluated. All three nano complexes, especially Pac, were able to increase cell viability, SOD and CAT activity, decreased Caspase 3 expression and prevented the generation of ROS and the loss of mitochondrial membrane potential caused by MPP(+). Pre-treatment with Pac and Paf nano complexes lead to a decrease of intracellular free Calcium, but Pas nano complex could not decrease it. Only Pac nano complex decreased MDA levels and other nano complexes could not change this parameter compared to MPP(+) treated cells. Hence according to the results, all nanochelating based nano complexes induced neuroprotective effects in an experimental model of PD, but the smallest nano complex, Pac, showed the best results.
帕金森病(PD)是世界上第二常见的痴呆症,现有的治疗药物除了减缓疾病进程外没有其他效果。最近,纳米技术为设计和制造用于神经退行性疾病的新药带来了契机。研究表明,通过调节纳米颗粒的大小,可以控制其生理效应。利用新型纳米螯合技术,设计了三种纳米复合物:Pas(150纳米)、Paf(100纳米)和Pac(40纳米),在本研究中,评估了它们在经1-甲基-4-苯基吡啶离子(MPP(+))处理的PC12细胞中的神经保护作用。PC12细胞先用Pas、Paf或Pac纳米复合物预处理,然后用10μM MPP(+)处理。随后,评估细胞活力、细胞内游离钙和活性氧(ROS)水平、线粒体膜电位、过氧化氢酶(CAT)和超氧化物歧化酶(SOD)活性、谷胱甘肽(GSH)和丙二醛(MDA)水平以及半胱天冬酶3表达。所有三种纳米复合物,尤其是Pac,都能够提高细胞活力、SOD和CAT活性,降低半胱天冬酶3表达,并防止MPP(+)引起的ROS生成和线粒体膜电位丧失。用Pac和Paf纳米复合物预处理导致细胞内游离钙减少,但Pas纳米复合物不能降低其水平。与MPP(+)处理的细胞相比,只有Pac纳米复合物降低了MDA水平,其他纳米复合物不能改变该参数。因此,根据结果,所有基于纳米螯合的纳米复合物在PD实验模型中均诱导了神经保护作用,但最小的纳米复合物Pac显示出最佳结果。