Antioxidant pharmacological therapies for COPD.

Antioxidant pharmacological therapies for COPD.
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DOI:
10.1016/j.coph.2012.01.015
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发表时间:
2012-06
影响因子:
4
通讯作者:
MacNee, William
MacNee, William
中科院分区:
医学3区
文献类型:
--
作者:
Rahman, Irfan;MacNee, William

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在慢性阻塞性肺病中,氧化应激增加发生在肺部和全身,它在慢性阻塞性肺病的许多致病机制中起作用。因此,用调节抗氧化剂/氧化还原系统或增强内源性抗氧化剂的药物靶向局部肺和全身氧化应激将是一种有用的COPD治疗方法。巯基抗氧化剂(n -乙酰- l-半胱氨酸和n -半胱氨酸、碳半胱氨酸、erdostein和fudostein)已被用于增加肺硫醇含量。据报道,香烟烟雾诱导的氧化应激及其引起的细胞变化的调节也受到合成分子的影响,如自旋诱捕剂(α-苯基- n -叔丁基硝基酮)、催化抗氧化剂(超氧化物歧化酶[ECSOD]模拟物)、卟啉、脂质过氧化和蛋白质羰基化阻滞剂/抑制剂(依达拉屈和lazaroids/替拉扎德)。临床前和临床试验表明,这些抗氧化剂可以减轻氧化应激,影响氧化还原和谷胱甘肽生物合成基因,以及促炎基因的表达。本文就提高慢性阻塞性肺病患者肺抗氧化剂的方法及抗氧化治疗对病程的潜在有益作用进行综述。
Increased oxidative stress occurs in the lungs and systemically in COPD, which plays a role in many of the pathogenic mechanisms in COPD. Hence, targeting local lung and systemic oxidative stress with agents that modulate the antioxidants/redox system or boost endogenous antioxidants would be a useful therapeutic approach in COPD. Thiol antioxidants (N-acetyl-L-cysteine and N-acystelyn, carbocysteine, erdosteine, and fudosteine have been used to increase lung thiol content. Modulation of cigarette smoke induced oxidative stress and its consequent cellular changes have also been reported to be effected by synthetic molecules, such as spin traps (α-phenyl-N-tert-butyl nitrone), catalytic antioxidants (superoxide dismutase [ECSOD] mimetics), porphyrins, and lipid peroxidation and protein carbonylation blockers/inhibitors (edaravone and lazaroids/tirilazad). Pre-clinical and clinical trials have shown that these antioxidants can reduce oxidative stress, affect redox and glutathione biosynthesis genes, and pro-inflammatory gene expression. In this review the approaches to enhance lung antioxidants in COPD and the potential beneficial effects of antioxidant therapy on the course of the disease are discussed.
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