Rahman Irfan
Department of Environmental Medicine, Lung Biology and Disease Program, University of Rochester Medical Center, NY 14642, USA.
Biochim Biophys Acta. 2012 May;1822(5):714-28. doi: 10.1016/j.bbadis.2011.11.004. Epub 2011 Nov 9.
Cigarette/tobacco smoke/biomass fuel-induced oxidative and aldehyde/carbonyl stress are intimately associated with the progression and exacerbation of chronic obstructive pulmonary disease (COPD). Therefore, targeting systemic and local oxidative stress with antioxidants/redox modulating agents, or boosting the endogenous levels of antioxidants are likely to have beneficial effects in the treatment/management of COPD. Various antioxidant agents, such as thiol molecules (glutathione and mucolytic drugs, such as N-acetyl-L-cysteine and N-acystelyn, erdosteine, fudosteine, ergothioneine, and carbocysteine), have been reported to modulate various cellular and biochemical aspects of COPD. These antioxidants have been found to scavenge and detoxify free radicals and oxidants, regulate of glutathione biosynthesis, control nuclear factor-kappaB (NF-kappaB) activation, and hence inhibiting inflammatory gene expression. Synthetic molecules, such as specific spin traps like α-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (ECSOD mimetic), porphyrins (AEOL 10150 and AEOL 10113), and a superoxide dismutase mimetic M40419, iNOS and myeloperoxidase inhibitors, lipid peroxidation inhibitors/blockers edaravone, and lazaroids/tirilazad have also been shown to have beneficial effects by inhibiting cigarette smoke-induced inflammatory responses and other carbonyl/oxidative stress-induced cellular alterations. A variety of oxidants, free radicals, and carbonyls/aldehydes are implicated in the pathogenesis of COPD, it is therefore, possible that therapeutic administration or supplementation of multiple antioxidants and/or boosting the endogenous levels of antioxidants will be beneficial in the treatment of COPD. This review discusses various novel pharmacological approaches adopted to enhance lung antioxidant levels, and various emerging beneficial and/or prophylactic effects of antioxidant therapeutics in halting or intervening the progression of COPD. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.
香烟/烟草烟雾/生物质燃料诱导的氧化应激以及醛/羰基应激与慢性阻塞性肺疾病（COPD）的进展和恶化密切相关。因此，使用抗氧化剂/氧化还原调节剂靶向全身和局部氧化应激，或提高内源性抗氧化剂水平，可能对COPD的治疗/管理产生有益效果。据报道，各种抗氧化剂，如硫醇分子（谷胱甘肽）和黏液溶解药物，如N-乙酰-L-半胱氨酸、N-乙酰半胱氨酸、厄多司坦、福多司坦、麦角硫因和羧甲司坦，可调节COPD的各种细胞和生化方面。已发现这些抗氧化剂可清除自由基和氧化剂并使其解毒，调节谷胱甘肽生物合成，控制核因子-κB（NF-κB）激活，从而抑制炎症基因表达。合成分子，如特定的自旋捕捉剂（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）以及超氧化物歧化酶模拟物M40419、诱导型一氧化氮合酶和髓过氧化物酶抑制剂、脂质过氧化抑制剂/阻滞剂依达拉奉以及拉扎罗类/替拉扎德，也已显示通过抑制香烟烟雾诱导的炎症反应和其他羰基/氧化应激诱导的细胞改变而具有有益效果。多种氧化剂、自由基以及羰基/醛类与COPD的发病机制有关，因此，治疗性给予或补充多种抗氧化剂和/或提高内源性抗氧化剂水平可能对COPD的治疗有益。本综述讨论了为提高肺抗氧化剂水平而采用的各种新型药理学方法，以及抗氧化剂治疗在阻止或干预COPD进展方面的各种新出现的有益和/或预防作用。本文是名为“疾病中的抗氧化剂和抗氧化剂治疗”的特刊的一部分。
