Rahman Md Mahbubur, Chakraborti Rupali Rani, Potol Md Abdullah, Abir Ariful Haque, Sharmin Ozayra, Alam Mahabub, Khan Md Fazlur Rahman, Afrin Rownock, Jannat Humayra, Wadud Rasiqh, Habib Zaki Farhad
Laboratory of Pharmacology Department of Pharmaceutical Sciences School of Health & Life Sciences North South University Dhaka Bangladesh.
Animal Model Exp Med. 2019 Dec 30;3(1):9-21. doi: 10.1002/ame2.12097. eCollection 2020 Mar.
Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting a large number of elderly people worldwide. The current therapies for PD are symptom-based; they do not provide a cure but improve the quality of life. Muscular dysfunction is the hallmark clinical feature of PD and oxidative stress and inflammation play a critical role in its pathogenesis. Epalrestat is used for the treatment of diabetic neuropathy and is known to improve antioxidative defense mechanisms in the CNS. Therefore, in this study, we investigated the role of Epalrestat in the reserpine induced mouse model of PD.
We used Swiss Albino mice for the PD model and tested for akinesia/bradykinesia, muscular rigidity, palpebral ptosis, and tremor, as well as conducting swim and open field tests. Brain samples were used to determine oxidative stress parameters and infiltration of immune cells.
Epalrestat treatment significantly improved akinesia and bradykinesia, muscular dysfunctions, tremor level, and gait functions compared to the reserpine group. It also improved the latency in the swim test. Eplarestat significantly reduced lipid peroxidation and NO concentration in different brain tissues and increased the activity of antioxidative enzymes, glutathione, catalase, and superoxide dismutase. Furthermore, Epalrestat reduced neuroinflammation by reducing the number of infiltrating immune cells.
Eplarestat improves muscular dysfunction in PD by reducing oxidative stress and inflammation.
帕金森病(PD)是一种进行性神经退行性疾病,影响着全球大量老年人。目前针对PD的治疗是基于症状的;它们不能治愈疾病,但能改善生活质量。肌肉功能障碍是PD的标志性临床特征,氧化应激和炎症在其发病机制中起关键作用。依帕司他用于治疗糖尿病性神经病变,已知其能改善中枢神经系统的抗氧化防御机制。因此,在本研究中,我们研究了依帕司他在利血平诱导的PD小鼠模型中的作用。
我们使用瑞士白化小鼠建立PD模型,并测试运动不能/运动迟缓、肌肉僵硬、眼睑下垂和震颤,以及进行游泳和旷场试验。使用脑样本确定氧化应激参数和免疫细胞浸润情况。
与利血平组相比,依帕司他治疗显著改善了运动不能和运动迟缓、肌肉功能障碍、震颤水平和步态功能。它还改善了游泳试验中的潜伏期。依帕司他显著降低了不同脑组织中的脂质过氧化和NO浓度,并增加了抗氧化酶、谷胱甘肽、过氧化氢酶和超氧化物歧化酶的活性。此外,依帕司他通过减少浸润免疫细胞的数量减轻了神经炎症。
依帕司他通过减轻氧化应激和炎症改善PD中的肌肉功能障碍。