Floyd R A
Molecular Toxicology Research Group, Oklahoma Medical Research Foundation, Oklahoma City 73104.
FASEB J. 1990 Jun;4(9):2587-97.
Even though oxygen is necessary for aerobic life, it can also participate in potentially toxic reactions involving oxygen free radicals and transition metals such as Fe that damage membranes, proteins, and nucleic acids. Oxygen free radical reactions and oxidative damage are in most cases held in check by antioxidant defense mechanisms, but where an excessive amount of oxygen free radicals are produced or defense mechanisms are impaired, oxidative damage may occur and this appears to be important in contributing to several pathological conditions including aging, carcinogenesis, and stroke. Several newer methods, such as in vivo spin-trapping, have become available to monitor oxygen free radical flux and quantitate oxidative damage. Using a combination of these newer methods collectively focused on one model, recent results show that oxidative damage plays a key role in brain injury that occurs in stroke. Subtle changes, such as oxidative damage-induced loss of glutamine synthetase activity, may be a key event in stroke-induced brain injury. Oxygen free radicals may play a key role in carcinogenesis by mediating formation of base adducts, such as 8-hydroxyguanine, which can now be quantitated to very low levels. Evidence is presented that a new class of free radical blocking agents, nitrone spin-traps, may help not only to clarify if free radical events are involved, but may help prevent the development of injury in certain pathological conditions.
尽管氧气是需氧生命所必需的，但它也会参与涉及氧自由基和过渡金属（如铁）的潜在毒性反应，这些反应会损害细胞膜、蛋白质和核酸。在大多数情况下，氧自由基反应和氧化损伤受到抗氧化防御机制的控制，但在产生过量氧自由基或防御机制受损的情况下，可能会发生氧化损伤，这似乎在导致包括衰老、致癌和中风在内的几种病理状况中起着重要作用。几种更新的方法，如体内自旋捕获法，已可用于监测氧自由基通量并定量氧化损伤。综合运用这些聚焦于同一模型的更新方法，最近的研究结果表明，氧化损伤在中风所致的脑损伤中起关键作用。细微的变化，如氧化损伤导致谷氨酰胺合成酶活性丧失，可能是中风所致脑损伤中的关键事件。氧自由基可能通过介导碱基加合物（如8-羟基鸟嘌呤）的形成在致癌过程中起关键作用，现在可以将其定量到极低水平。有证据表明，一类新型的自由基阻断剂——硝酮自旋捕获剂，不仅可能有助于阐明是否涉及自由基事件，还可能有助于预防某些病理状况下损伤的发展。
