Antioxidant therapeutic advances in COPD.
Antioxidant therapeutic advances in COPD.
复制标题
COPD中的抗氧化治疗进展。
DOI：
10.1177/1753465808098224
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发表时间：
2008-12
影响因子：
4.3
通讯作者：
Rahman I
中科院分区：
文献类型：
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作者：
Rahman I
慢性阻塞性肺疾病（COPD）是一种发病率和死亡率较高的疾病。氧化应激与COPD的进展和恶化密切相关，因此用抗氧化剂靶向氧化应激或提高内源性抗氧化剂水平可能在COPD的治疗中具有有益的结果。在迄今为止尝试的各种抗氧化剂中，硫醇抗氧化剂和粘液溶解剂，如谷胱甘肽、N-乙酰基-L-半胱氨酸、N-乙酰半胱氨酸蛋白酶、厄多司坦、福多司坦和羧半胱氨酸; Nrf 2活化剂和膳食多酚（姜黄素、白藜芦醇、绿色茶和儿茶素/槲皮素）已被报道增加细胞内硫醇状态以及GSH生物合成的诱导。巯基状态的这种升高反过来导致自由基和氧化剂的解毒以及对正在进行的炎症反应的抑制。此外，还报道了特定的自旋陷阱，例如α-苯基-N-叔丁基硝酮、催化抗氧化剂（ECSOD模拟物）、卟啉（AEOL 10150和AEOL 10113）和SOD模拟物M40419，在体内抑制香烟烟雾诱导的肺中的炎症反应。由于多种氧化剂、自由基和醛类参与COPD的发病机制，因此多种抗氧化剂和粘液溶解剂的治疗性给药可能在COPD的管理中有效。然而，一个成功的结果将严重依赖于抗氧化治疗的选择，为特定的临床表型的COPD，其病理生理学应首先得到正确的理解。本文将综述提高肺抗氧化水平的各种方法，抗氧化治疗进展和抗氧化化合物在COPD中的临床试验。
Chronic obstructive pulmonary disease (COPD) is associated with high incidence of morbidity and mortality. Oxidative stress is intimately associated with the progression and exacerbation of COPD and therefore targeting oxidative stress with antioxidants or boosting the endogenous levels of antioxidants is likely to have beneficial outcome in the treatment of COPD. Among the various antioxidants tried so far, thiol antioxidants and mucolytic agents, such as glutathione, N-acetyl-L-cysteine, N-acystelyn, erdosteine, fudosteine, and carbocysteine; Nrf2 activators, and dietary polyphenols (curcumin, resveratrol, green tea, and catechins/quercetin) have been reported to increase intracellular thiol status alongwith induction of GSH biosynthesis. Such an elevation in the thiol status in turn leads to detoxification of free radicals and oxidants as well as inhibition of ongoing inflammatory responses. In addition, specific spin traps, such as a-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (ECSOD mimetic), porphyrins (AEOL 10150 and AEOL 10113), and a SOD mimetic M40419 have also been reported to inhibit cigarette smoke-induced inflammatory responses in vivo in the lung. Since a variety of oxidants, free radicals and aldehydes are implicated in the pathogenesis of COPD; it is possible that therapeutic administration of multiple antioxidants and mucolytics will be effective in management of COPD. However, a successful outcome will critically depend upon the choice of antioxidant therapy for a particular clinical phenotype of COPD, whose pathophysiology should be first properly understood. This article will review the various approaches adopted to enhance lung antioxidant levels, antioxidant therapeutic advances and recent past clinical trials of antioxidant compounds in COPD.