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使用Wistar大鼠原代皮质神经元培养研究唑吡坦对丙烯酰胺诱导的神经毒性的抗氧化和神经保护作用。

The antioxidant and neuroprotective effects of Zolpidem on acrylamide-induced neurotoxicity using Wistar rat primary neuronal cortical culture.

作者信息

Yousefsani Bahareh Sadat, Akbarizadeh Nasim, Pourahmad Jalal

机构信息

Research Institute for Islamic and Complementary Medicine, Iran University of Medical Sciences, Tehran, Iran.

School of Persian Medicine, Iran University of Medical Sciences, Tehran, Iran.

出版信息

Toxicol Rep. 2020 Jan 27;7:233-240. doi: 10.1016/j.toxrep.2020.01.010. eCollection 2020.

Abstract

Zolpidem is an introduced medication for the therapy of sleeping disorders. Its pharmacological effects are consequently characterized by a quick onset and a half-life of 2.4 h. Previous studies revealed the antioxidant and neuroprotectant effects of zolpidem. In this research, we wanted to demonstrate the exact sub-cellular/molecular mechanism of this medication using the primary neuronal cortical culture. For this purpose, firstly, the cortical neurons were isolated from the postnatal Wistar rat pups. Thereafter, different neural toxicity endpoints caused by acrylamide including ROS formation, lipid peroxidation, mitochondrial membrane potential collapse, lysosomal membrane integrity, and apoptosis were determined. All of these parameters are upstream events of cellular apoptosis which justifies neurodegeneration involved in many diseases such as Alzheimer's and Parkinson's. Our results demonstrated that zolpidem at concentrations of 1 and 2 mM prevented all the acrylamide-induced above referenced neural toxic events leading to neuronal apoptosis. These results revealed that zolpidem has the antioxidant and neuroprotectant properties that make it a promising prophylactic agent for preventing neurodegenerative complications. Considering the important role of oxidative stress in the development or progression of diseases, if the medication used as a treatment of a disease has antioxidant properties at the same time, it will certainly have much greater healing effects.

摘要

唑吡坦是一种用于治疗睡眠障碍的药物。因此,其药理作用的特点是起效快,半衰期为2.4小时。先前的研究揭示了唑吡坦的抗氧化和神经保护作用。在本研究中,我们希望使用原代皮质神经元培养来证明这种药物确切的亚细胞/分子机制。为此,首先从新生Wistar大鼠幼崽中分离出皮质神经元。此后,测定了丙烯酰胺引起的不同神经毒性终点,包括活性氧形成、脂质过氧化、线粒体膜电位崩溃、溶酶体膜完整性和细胞凋亡。所有这些参数都是细胞凋亡的上游事件,这解释了许多疾病(如阿尔茨海默病和帕金森病)中涉及的神经退行性变。我们的结果表明,浓度为1 mM和2 mM的唑吡坦可预防所有丙烯酰胺诱导的上述神经毒性事件,从而导致神经元凋亡。这些结果表明,唑吡坦具有抗氧化和神经保护特性,使其成为预防神经退行性并发症的有前景的预防药物。考虑到氧化应激在疾病发生或发展中的重要作用,如果用作治疗疾病的药物同时具有抗氧化特性,它肯定会有更大的治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20f6/6997640/5770066c0d60/ga1.jpg

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