Department of Chemistry, Faculty of Natural Sciences, Constantine the Philosopher University in Nitra, Nitra, 949 74, Slovakia.
Faculty of Chemical and Food Technology, Slovak University of Technology, Bratislava, 812 37, Slovakia.
Arch Toxicol. 2023 Oct;97(10):2499-2574. doi: 10.1007/s00204-023-03562-9. Epub 2023 Aug 19.
A physiological level of oxygen/nitrogen free radicals and non-radical reactive species (collectively known as ROS/RNS) is termed oxidative eustress or "good stress" and is characterized by low to mild levels of oxidants involved in the regulation of various biochemical transformations such as carboxylation, hydroxylation, peroxidation, or modulation of signal transduction pathways such as Nuclear factor-κB (NF-κB), Mitogen-activated protein kinase (MAPK) cascade, phosphoinositide-3-kinase, nuclear factor erythroid 2-related factor 2 (Nrf2) and other processes. Increased levels of ROS/RNS, generated from both endogenous (mitochondria, NADPH oxidases) and/or exogenous sources (radiation, certain drugs, foods, cigarette smoking, pollution) result in a harmful condition termed oxidative stress ("bad stress"). Although it is widely accepted, that many chronic diseases are multifactorial in origin, they share oxidative stress as a common denominator. Here we review the importance of oxidative stress and the mechanisms through which oxidative stress contributes to the pathological states of an organism. Attention is focused on the chemistry of ROS and RNS (e.g. superoxide radical, hydrogen peroxide, hydroxyl radicals, peroxyl radicals, nitric oxide, peroxynitrite), and their role in oxidative damage of DNA, proteins, and membrane lipids. Quantitative and qualitative assessment of oxidative stress biomarkers is also discussed. Oxidative stress contributes to the pathology of cancer, cardiovascular diseases, diabetes, neurological disorders (Alzheimer's and Parkinson's diseases, Down syndrome), psychiatric diseases (depression, schizophrenia, bipolar disorder), renal disease, lung disease (chronic pulmonary obstruction, lung cancer), and aging. The concerted action of antioxidants to ameliorate the harmful effect of oxidative stress is achieved by antioxidant enzymes (Superoxide dismutases-SODs, catalase, glutathione peroxidase-GPx), and small molecular weight antioxidants (vitamins C and E, flavonoids, carotenoids, melatonin, ergothioneine, and others). Perhaps one of the most effective low molecular weight antioxidants is vitamin E, the first line of defense against the peroxidation of lipids. A promising approach appears to be the use of certain antioxidants (e.g. flavonoids), showing weak prooxidant properties that may boost cellular antioxidant systems and thus act as preventive anticancer agents. Redox metal-based enzyme mimetic compounds as potential pharmaceutical interventions and sirtuins as promising therapeutic targets for age-related diseases and anti-aging strategies are discussed.
生理水平的氧/氮自由基和非自由基反应性物质（统称为 ROS/RNS）被称为氧化应激或“良性应激”，其特征是涉及各种生化转化的氧化剂水平低至中度，如羧化、羟化、过氧化或调节信号转导途径，如核因子-κB（NF-κB）、丝裂原激活蛋白激酶（MAPK）级联、磷酸肌醇-3-激酶、核红细胞 2 相关因子 2（Nrf2）和其他过程。ROS/RNS 水平的增加，源自内源性（线粒体、NADPH 氧化酶）和/或外源性来源（辐射、某些药物、食物、吸烟、污染），导致一种称为氧化应激（“不良应激”）的有害状态。尽管人们普遍认为许多慢性疾病的起源是多因素的，但它们都有氧化应激作为共同的因素。在这里，我们回顾了氧化应激的重要性以及氧化应激导致生物体病理状态的机制。重点关注 ROS 和 RNS 的化学性质（例如超氧自由基、过氧化氢、羟基自由基、过氧自由基、一氧化氮、过氧亚硝酸盐）及其在 DNA、蛋白质和膜脂质的氧化损伤中的作用。还讨论了氧化应激生物标志物的定量和定性评估。氧化应激导致癌症、心血管疾病、糖尿病、神经退行性疾病（阿尔茨海默病和帕金森病、唐氏综合征）、精神疾病（抑郁症、精神分裂症、双相情感障碍）、肾脏疾病、肺部疾病（慢性阻塞性肺病、肺癌）和衰老。抗氧化剂通过抗氧化酶（超氧化物歧化酶-SODs、过氧化氢酶、谷胱甘肽过氧化物酶-GPx）和小分子抗氧化剂（维生素 C 和 E、类黄酮、类胡萝卜素、褪黑素、麦角硫因等）来减轻氧化应激的有害影响。也许最有效的小分子抗氧化剂之一是维生素 E，它是防止脂质过氧化的第一道防线。一种有前途的方法似乎是使用某些抗氧化剂（例如类黄酮），这些抗氧化剂具有较弱的促氧化剂特性，可能会增强细胞抗氧化系统，从而作为预防癌症的药物。还讨论了基于氧化还原金属的酶模拟化合物作为潜在的药物干预以及作为与年龄相关疾病和抗衰老策略相关的有希望的治疗靶点的 Sirtuins。
