Silva J P, Coutinho O P
GCBMA - Molecular and Environmental Biology Centre, Department of Biology, University of Minho, Braga, Portugal.
Drug Discov Ther. 2010 Jun;4(3):144-67.
Reactive oxygen (ROS) and nitrogen (RNS) species are known to accumulate intracellularly due to both exogenous and/or endogenous factors. In normal physiological conditions, these reactive species are maintained in an equilibrium state by the cells' antioxidant defence systems. In addition, they are recognised to play important roles in several physiological functions. However, when an imbalance in the equilibrium between oxidants and antioxidants occurs in favour of the former, we come to a situation defined as oxidative stress. ROS/RNS can cause damage to all biomolecules (namely proteins, lipids and DNA) and ultimately participate in the regulation of mechanisms leading to cell death, being implicated in the etiology of several pathologies (like neurodegenerative and cardiovascular diseases). To cope with oxidative stress, cells possess effective enzymatic (e.g. superoxide dismutase, catalase, glutathione peroxidase) and non-enzymatic (e.g. glutathione, thioredoxin, coenzyme Q) antioxidant systems. In addition, several compounds present in plants and vegetables (e.g. vitamins C and E, polyphenols) have been described to react with free radicals. However, some drawbacks associated to these natural compounds are in part responsible for the undergoing development of novel synthetic compounds capable of acting as antioxidants and protect cells against oxidative stress-induced cell death. Here, we review the basic mechanisms of ROS/RNS formation, as well as their interaction with biomolecules and regulation of cell death, in order to identify possible drug targets. We also report the importance of natural antioxidant systems and the ongoing research leading to the development of more powerful and effective antioxidant drugs.
已知由于外源性和/或内源性因素，活性氧（ROS）和活性氮（RNS）会在细胞内积累。在正常生理条件下，这些活性物质通过细胞的抗氧化防御系统维持在平衡状态。此外，人们认识到它们在多种生理功能中发挥重要作用。然而，当氧化剂和抗氧化剂之间的平衡发生失衡，且有利于前者时，就会出现一种被定义为氧化应激的情况。ROS/RNS会对所有生物分子（即蛋白质、脂质和DNA）造成损害，并最终参与导致细胞死亡的机制调节，与多种疾病（如神经退行性疾病和心血管疾病）的病因有关。为了应对氧化应激，细胞拥有有效的酶促抗氧化系统（如超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶）和非酶促抗氧化系统（如谷胱甘肽、硫氧还蛋白、辅酶Q）。此外，已描述植物和蔬菜中存在的几种化合物（如维生素C和E、多酚）可与自由基发生反应。然而，与这些天然化合物相关的一些缺点在一定程度上促使了能够作为抗氧化剂并保护细胞免受氧化应激诱导的细胞死亡的新型合成化合物的开发。在此，我们综述ROS/RNS形成的基本机制，以及它们与生物分子的相互作用和细胞死亡的调节，以确定可能的药物靶点。我们还报告了天然抗氧化系统的重要性以及导致开发更强大、更有效的抗氧化药物的正在进行的研究。
