University of Agronomic Sciences and Veterinary Medicine of Bucharest, Faculty of Veterinary Medicine, 105 Splaiul Independentei, 050097, Bucharest, Romania.
University of Agronomic Sciences and Veterinary Medicine of Bucharest, Faculty of Veterinary Medicine, 105 Splaiul Independentei, 050097, Bucharest, Romania.
Eur J Med Chem. 2021 Jan 1;209:112891. doi: 10.1016/j.ejmech.2020.112891. Epub 2020 Sep 30.
The present review paper focuses on the chemistry of oxidative stress mitigation by antioxidants. Oxidative stress is understood as a lack of balance between the pro-oxidant and the antioxidant species. Reactive oxygen species in limited amounts are necessary for cell homeostasis and redox signaling. Excessive reactive oxygenated/nitrogenated species production, which counteracts the organism's defense systems, is known as oxidative stress. Sustained attack of endogenous and exogenous ROS results in conformational and oxidative alterations in key biomolecules. Chronic oxidative stress is associated with oxidative modifications occurring in key biomolecules: lipid peroxidation, protein carbonylation, carbonyl (aldehyde/ketone) adduct formation, nitration, sulfoxidation, DNA impairment such strand breaks or nucleobase oxidation. Oxidative stress is tightly linked to the development of cancer, diabetes, neurodegeneration, cardiovascular diseases, rheumatoid arthritis, kidney disease, eye disease. The deleterious action of reactive oxygenated species and their role in the onset and progression of pathologies are discussed. The results of oxidative attack become themselves sources of oxidative stress, becoming part of a vicious cycle that amplifies oxidative impairment. The term antioxidant refers to a compound that is able to impede or retard oxidation, acting at a lower concentration compared to that of the protected substrate. Antioxidant intervention against the radicalic lipid peroxidation can involve different mechanisms. Chain breaking antioxidants are called primary antioxidants, acting by scavenging radical species, converting them into more stable radicals or non-radical species. Secondary antioxidants quench singlet oxygen, decompose peroxides, chelate prooxidative metal ions, inhibit oxidative enzymes. Moreover, four reactivity-based lines of defense have been identified: preventative antioxidants, radical scavengers, repair antioxidants, and those relying on adaptation mechanisms. The specific mechanism of a series of endogenous and exogenous antioxidants in particular aspects of oxidative stress, is detailed. The final section resumes critical conclusions regarding antioxidant supplementation.
本文综述了抗氧化剂缓解氧化应激的化学。氧化应激被理解为促氧化剂和抗氧化剂之间的不平衡。适量的活性氧是细胞内稳态和氧化还原信号所必需的。过多的活性氧/氮物种的产生，对抗机体的防御系统，被称为氧化应激。内源性和外源性 ROS 的持续攻击会导致关键生物分子的构象和氧化改变。慢性氧化应激与关键生物分子中发生的氧化修饰有关：脂质过氧化、蛋白质羰基化、羰基（醛/酮）加合物形成、硝化、亚砜化、DNA 损伤如链断裂或核碱基氧化。氧化应激与癌症、糖尿病、神经退行性疾病、心血管疾病、类风湿性关节炎、肾病、眼病的发展密切相关。活性氧的有害作用及其在发病机制中的作用被讨论。氧化攻击的结果本身就是氧化应激的来源，成为放大氧化损伤的恶性循环的一部分。抗氧化剂是指能够阻碍或延缓氧化的化合物，其作用浓度低于被保护底物的浓度。抗氧化剂干预自由基脂质过氧化可以涉及不同的机制。链断裂抗氧化剂被称为初级抗氧化剂，通过清除自由基，将其转化为更稳定的自由基或非自由基物质来发挥作用。二次抗氧化剂猝灭单线态氧、分解过氧化物、螯合促氧化剂金属离子、抑制氧化酶。此外，已经确定了基于四种反应性的防御线：预防性抗氧化剂、自由基清除剂、修复抗氧化剂和依赖于适应机制的抗氧化剂。详细描述了一系列内源性和外源性抗氧化剂在氧化应激特定方面的特定机制。最后一部分总结了关于抗氧化剂补充的关键结论。
