Nordmann R
Département de Recherches Biomédicales sur l'Alcoolisme, Biomédicale des Saints-Pères, Paris.
C R Seances Soc Biol Fil. 1993;187(3):277-85.
Free radicals having oxidizing properties are produced in vivo. The monoelectronic reduction of dioxygen generates the superoxide radical (.O2-) which, according to the experimental conditions, behaves as a reducing or an oxidizing agent. Its dismutation catalyzed by superoxide dismutases (SODs) produces hydrogen peroxide. The latter reacting with .O2- in the presence of "redox-active" iron produces highly aggressive prooxidant radicals, such as the hydroxyl radical (.OH). This production is prevented through intracellular enzymes (catalase and glutathione peroxidases) which destroy the hydrogen peroxide involved in the biosynthesis of .OH. An increase in SODs activity without parallel enhancement of the enzymes destroying H2O2 may lead to important cellular disturbances. Other enzymes acting with glutathione as substrate (especially glutathione S-transferases) contribute to the antioxidant defence. The same holds true for selenium and zinc which act mainly through their involvement in the structure of both antioxidant enzymes and nonenzymatic proteins. Another line of antioxidant defence is represented by substrates acting as chain-breaking antioxidants in destructive processes linked to prooxidant free radicals, such as lipid peroxidation. The main membranous antioxidant is alpha-tocopherol which is able to quench efficiently lipid peroxyl radicals. Its efficiency would be quickly exhausted if the tocopheryl radical formed during this reaction wouldn't be retransformed into alpha-tocopherol through the intervention of ascorbate and/or glutathione. Ubiquinol and dihydrolipoate also contribute to the membranous antioxidant defence, whereas carotenoids are mainly responsible for the prevention of the deleterious effects of singlet oxygen. An oxidative stress is apparent when the antioxidant defence is insufficient to cope with the prooxidant production.
体内会产生具有氧化特性的自由基。双原子氧的单电子还原会产生超氧阴离子自由基（·O₂⁻），根据实验条件，它可作为还原剂或氧化剂。超氧化物歧化酶（SOD）催化其歧化反应会产生过氧化氢。在“氧化还原活性”铁存在的情况下，过氧化氢与·O₂⁻反应会产生极具攻击性的促氧化自由基，如羟基自由基（·OH）。细胞内的酶（过氧化氢酶和谷胱甘肽过氧化物酶）会破坏参与·OH生物合成的过氧化氢，从而阻止这种产生。超氧化物歧化酶活性增加而破坏过氧化氢的酶没有相应增强，可能会导致重要的细胞紊乱。其他以谷胱甘肽为底物起作用的酶（尤其是谷胱甘肽S -转移酶）有助于抗氧化防御。硒和锌也是如此，它们主要通过参与抗氧化酶和非酶蛋白的结构来发挥作用。抗氧化防御的另一个方面是由在与促氧化自由基相关的破坏过程中作为链断裂抗氧化剂起作用的底物所代表的，例如脂质过氧化。主要的膜抗氧化剂是α -生育酚，它能够有效淬灭脂质过氧自由基。如果在此反应过程中形成的生育酚自由基不能通过抗坏血酸和/或谷胱甘肽的介入重新转化为α -生育酚，其效率会很快耗尽。泛醇和二氢硫辛酸也有助于膜抗氧化防御，而类胡萝卜素主要负责防止单线态氧的有害影响。当抗氧化防御不足以应对促氧化剂的产生时，氧化应激就会明显出现。
