Reactive oxygen species in human health and disease
Reactive oxygen species in human health and disease
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DOI：
10.1016/s0899-9007(00)00570-0
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发表时间：
2001-02-01
期刊：
影响因子：
4.4
通讯作者：
Freeman, B
中科院分区：
文献类型：
--
作者：
Castro, L;Freeman, B
在过去的30年里，自由基化学和生物学领域已经从相对默默无闻的发展成为生物医学研究和药物开发的主流元素。越来越多的证据表明，氧化应激，定义为氧化剂和抗氧化剂之间的不平衡，有利于前者，导致有害的生化反应，是几种慢性人类疾病的重要促成因素，包括动脉粥样硬化和相关的血管疾病，诱变和癌症，神经变性，免疫紊乱，甚至是衰老过程。我们理解的氧自由基介导氧毒性的第一个直接证据出现在1954年，当时Dalla Gerschman，丹尼尔吉尔伯特，及其同事指出，X射线对肺组织的损伤模式与高氧浓度引起的损伤模式相似。[1]在他们的工作中，通过引用以前的观察结果和提出新的数据，证明了这两种病理现象的相似性，这些数据显示了高氧和X射线照射的累积效应。他们还报告说，许多化学剂提供保护，防止辐射的毒性作用，也防止氧中毒。他们的理论的基本特征是，氧中毒和x射线照射的生物效应都有一个共同的作用机制，特别是自由基的反应。正如杜克大学生物化学教授欧文·弗里多维奇所说：“考虑到当时有关特定自由基产生和清除的信息很少，这是一个非常有先见之明的理论”。[2] 1969年，Joe McCord和欧文Fridovich通过确定酶超氧化物歧化酶（SOD）的催化功能，[3]进一步巩固了氧毒性的自由基介导的概念，为体内产生超氧化物自由基提供了直接的分析证据。从随后对精细的组织抗氧化防御的阐明和对组织炎性损伤机制的洞察的快速演变中，Gerschman，吉尔伯特及其同事的开创性理论获得了力量，并超越了对生物学和医学多个方面的革命性理解。
During the past 30 years, the fields of free radical chemistry and biology have risen from relative obscurity to become mainstream elements of biomedical investigation and pharmaceutical development. There is increasing evidence that oxidative stress, defined as an imbalance between oxidants and antioxidants in favor of the former, leads to detrimental biochemical reactions and is an important contributing factor in several chronic human diseases, including atherosclerosis and related vascular diseases, mutagenesis and cancer, neurodegeneration, immunologic disorders, and even the aging process.The first direct proof in our understanding that oxygen free radicals mediated oxygen toxicity appeared in 1954, when Rebeca Gerschman, Daniel Gilbert, and colleagues noted that the pattern of x-radiation damage to lung tissue was similar to that induced by high oxygen concentrations. 1 In their work, the similarity of these two pathologic phenomena was established, by both citation of previous observations and by the presentation of new data showing the cumulative effects of hyperoxia and x-irradiation. They also reported that many chemical agents affording protection against the toxic effect of radiation also protected against oxygen poisoning. The essential feature of their theory was that both oxygen poisoning and the biological effects of x-irradiation share a common mechanism of action, specifically the reactions of free radicals. As stated by Irwin Fridovich, a Professor of Biochemistry at Duke University:“This was a remarkably prescient theory, considering the paucity of information concerning the generation and scavenging of specific free radicals available at that time”. 2 In 1969, Joe McCord and Irwin Fridovich went on to solidify the concept of free radical mediation of oxygen toxicity by identifying a catalytic function for the enzyme superoxide dismutase (SOD), 3 providing direct analytical evidence of the in vivo generation of the superoxide radical. From the subsequent elucidation of elaborate tissue antioxidant defenses and a rapid evolution of insight into mechanisms of tissue inflammatory injury, the seminal theory of Gerschman, Gilbert, and colleagues gained force and transcended into a revolutionary understanding of multiple facets of biology and medicine.