Shaki Fatemeh, Shayeste Yaghoub, Karami Mohammad, Akbari Esmaeil, Rezaei Mahdi, Ataee Ramin
Department of Toxicology and Pharmacology and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, I.R. Iran.
Department of Physiology and Pharmacology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, I.R. Iran.
Res Pharm Sci. 2017 Apr;12(2):119-127. doi: 10.4103/1735-5362.202450.
Oxidative stress and mitochondrial dysfunction are the main suggested mechanisms for neurodegenerative diseases. In this study, we have evaluated the effects of epicatechin (EC) on mitochondrial damage induced by homocycteine (Hcy) using isolated rat hippocampus mitochondria . EC (50 mg/kg) was gavaged daily for a period of 10 days, starting 5 days prior to Hcy (0.5 μmol/μL) intra hippocampus injection in rats. Mitochondria were isolated from brain by different centrifuge techniques. Mitochondrial function was assayed by MTT test. Also, mitochondrial swelling and oxidative stress markers, such as reactive oxygen species (ROS), lipid peroxidation and glutathione (GSH), were assayed. Hcy induced mitochondrial dysfunction and swelling. Increase in ROS formation, lipid peroxidation, and decreased GSH were observed after Hcy treatment in isolated brain mitochondria. Furthermore, oral administration of EC significantly decreased the lipid peroxidation and ROS levels and also increased GSH levels. Also, EC treatment significantly improved mitochondrial function. As EC indicated protective effects against oxidative stress and mitochondrial damage induced by Hcy, it is suggested for further trials for prevention or treatments of neurodegenerative disorders such as Alzheimer disease.
氧化应激和线粒体功能障碍是神经退行性疾病主要的潜在机制。在本研究中，我们使用分离的大鼠海马线粒体评估了表儿茶素（EC）对同型半胱氨酸（Hcy）诱导的线粒体损伤的影响。在大鼠海马内注射Hcy（0.5μmol/μL）前5天开始，每天灌胃给予EC（50mg/kg），持续10天。通过不同的离心技术从大脑中分离出线粒体。通过MTT试验检测线粒体功能。此外，还检测了线粒体肿胀和氧化应激标志物，如活性氧（ROS）、脂质过氧化和谷胱甘肽（GSH）。Hcy诱导线粒体功能障碍和肿胀。在分离的脑线粒体中，Hcy处理后观察到ROS生成增加、脂质过氧化增加以及GSH减少。此外，口服EC可显著降低脂质过氧化和ROS水平，还可提高GSH水平。而且，EC处理显著改善了线粒体功能。由于EC对Hcy诱导的氧化应激和线粒体损伤具有保护作用，因此建议进一步试验以预防或治疗神经退行性疾病，如阿尔茨海默病。
