Translational research involving oxidative stress and diseases of aging.
Translational research involving oxidative stress and diseases of aging.
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DOI：
10.1016/j.freeradbiomed.2011.04.014
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发表时间：
2011-09-01
影响因子：
7.4
通讯作者：
Maples, Kirk R.
中科院分区：
文献类型：
--
作者：
Floyd, Robert A.;Towner, Rheal A.;He, Ting;Hensley, Kenneth;Maples, Kirk R.
关键词：
越来越多的证据表明，在炎症过程、许多病理条件和慢性年龄相关疾病的潜在过程中，活性氧化物质会加剧。因此，人们越来越期望能够开发出以某种方式抑制活性氧化物质并改善病情的治疗方法。事实证明，这比最初预期的要困难得多。发展治疗的适应症，其中反应性氧化剂是重要的考虑提出了一些独特的挑战。我们讨论了一些重要的问题，包括是否应将活性氧化剂作为治疗靶点，是否需要认识到特定化学系统中的抗氧化剂在生物系统中可能是不良抗氧化剂这一事实，以及考虑到活性氧化剂可能伴随疾病或病理系统而不是致病因素这一事实的重要性。我们还讨论了拥有临床前模型的价值，以确定在引起所研究疾病的重要过程是否严重依赖于反应性氧化剂物种事件，以及正在考虑的治疗是否平息了这些过程。此外，我们还讨论了在临床前和临床试验的商业研究和开发中必须满足的成功标准，并作为例子讨论了我们在开发用于治疗急性缺血性中风和抗癌药物的硝基酮方面的转化研究工作。
There is ample mounting evidence that reactive oxidant species are exacerbated in inflammatory processes, many pathological conditions and underlying processes of chronic age-related diseases. Therefore there is increased expectation that therapeutics can be developed which act in some fashion to suppress reactive oxidant species and ameliorate the condition. This has turned out to be more difficult than at first expected. Developing therapeutics for indications where reactive oxidant species is an important consideration presents some unique challenges. We discuss important questions including whether reactive oxidant species should be a therapeutic target and the need to recognize the fact that an antioxidant in a defined chemical system may be a poor antioxidant operationally in a biological system and the importance of considering the fact that reactive oxidant species may accompany the disease or pathological system rather than being a causative factor. We also discuss the value of having preclinical models to determine if the processes which are important in causing the disease under study is critically dependent on reactive oxidant species events and if the therapeutic under consideration quells these processes. In addition we discuss measures of success that must be met in commercial research and development in preclinical and clinical trials and discuss as examples our translational research effort in developing nitrones for the treatment of acute ischemic stroke and as anti-cancer agents.
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影响因子：
7.4
作者：
Choi, Chul-Hee;Chen, Kejian;Kopke, Richard D.
通讯作者：
Kopke, Richard D.
影响因子：
4.4
作者：
Asanuma, Taketoshi;Doblas, Sabrina;Towner, Rheal A.
通讯作者：
Towner, Rheal A.
DOI：
10.1073/pnas.88.9.3633
发表时间：
1991-05-01
影响因子：
11.1
作者：
CARNEY, JM;STARKEREED, PE;FLOYD, RA
通讯作者：
FLOYD, RA
DOI：
10.1016/0748-5514(86)90118-2
发表时间：
1986-01-01
期刊：
Journal of Free Radicals in Biology and Medicine
影响因子：
--
作者：
FLOYD R A;HENDERSON R;WONG P K
通讯作者：
WONG P K
影响因子：
2.5
作者：
CAO, W;CARNEY, JM;CHEVION, M
通讯作者：
CHEVION, M