Abstract：
Probucol is a hyperlipidemic drug with antioxidant properties. It has been reported to prevent mitochondrial dysfunction, reduce oxidative stress, and suppress neurotoxicity in neurodegenerative disease models, including Parkinson\'s disease models. However, the molecular mechanisms underlying the neuroprotective effects of probucol have been not examined yet. Thus, in this study, we investigated whether probucol can alleviate the effects of a mitochondrial complex I inhibitor, rotenone, on a human neuroblastoma cell line (SH-SY5Y). We evaluated the cell viability and cytotoxicity and apoptosis rates of SH-SY5Y cells treated with rotenone and probucol or edaravone, a known free-radical scavenger. Subsequently, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels in the cells were evaluated to determine the effects of probucol on mitochondrial function. We found that rotenone caused cytotoxicity, cell apoptosis, and mitochondrial dysfunction, enhanced ROS generation, and impaired MMP. However, probucol could inhibit this rotenone-induced decrease in cell viability, MMP loss, intracellular ROS generation, and apoptosis. These results suggest that probucol exerts neuroprotective effects via MMP stabilization and the inhibition of ROS generation. Additionally, this effect of probucol was equal to or greater than and more persistent than that of edaravone. Thus, we believe probucol may be a promising drug for the treatment of neurodegenerative diseases, such as Parkinson\'s and Alzheimer\'s diseases.
摘要：
普罗布考是一种具有抗氧化特性的高脂血症药物。据报道，它可以预防线粒体功能障碍，减少氧化应激，并抑制神经退行性疾病模型中的神经毒性，包括帕金森病模型。然而,普罗布考神经保护作用的分子机制尚未被研究。因此，在这项研究中，我们研究了普罗布考是否可以减轻线粒体复合物I抑制剂的作用，鱼藤酮,在人神经母细胞瘤细胞系(SH-SY5Y)上。我们评估了用鱼藤酮和普罗布考或依达拉奉处理的SH-SY5Y细胞的细胞活力，细胞毒性和凋亡率，一种已知的自由基清除剂.随后，评估细胞中线粒体膜电位(MMP)和活性氧(ROS)水平,以确定普罗布考对线粒体功能的影响.我们发现鱼藤酮引起细胞毒性,细胞凋亡，和线粒体功能障碍，增强ROS生成，MMP受损。然而,普罗布考能抑制鱼藤酮诱导的细胞活力下降，MMP损失，细胞内ROS的产生，和凋亡。这些结果表明，普罗布考通过稳定MMP和抑制ROS产生发挥神经保护作用。此外,普罗布考的这种作用等于或大于依达拉奉的作用,且比依达拉奉的作用更持久.因此，我们相信普罗布考可能是治疗神经退行性疾病的有前途的药物，如帕金森病和阿尔茨海默病。
