Department of Biochemistry, Dr. Ambedkar College, Deeksha Bhoomi, Nagpur 440010, MS, India.
Curr Med Chem. 2013;20(12):1496-530. doi: 10.2174/0929867311320120004.
The progression and exacerbations of chronic obstructive pulmonary disease (COPD) are intimately associated with tobacco smoke/biomass fuel-induced oxidative and aldehyde/carbonyl stress. Alterations in redox signaling proinflammatory kinases and transcription factors, steroid resistance, unfolded protein response, mucus hypersecretion, extracellular matrix remodeling, autophagy/apoptosis, epigenetic changes, cellular senescence/aging, endothelial dysfunction, autoimmunity, and skeletal muscle dysfunction are some of the pathological hallmarks of COPD. In light of the above it would be prudent to target systemic and local oxidative stress with agents that can modulate the antioxidants/ redox system or by boosting the endogenous levels of antioxidants for the treatment and management of COPD. Identification of various antioxidant agents, such as thiol molecules (glutathione and mucolytic drugs, such as N-acetyl-L-cysteine, N-acystelyn, erdosteine, fudosteine, ergothioneine, and carbocysteine lysine salt), dietary natural product-derived polyphenols and other compounds (curcumin, resveratrol, green tea catechins, quercetin sulforaphane, lycopene, acai, alpha-lipoic acid, tocotrienols, and apocynin) have made it possible to modulate various biochemical aspects of COPD. Various researches and clinical trials have revealed that these antioxidants can detoxify free radicals and oxidants, control expression of redox and glutathione biosynthesis genes, chromatin remodeling, and ultimately inflammatory gene expression. In addition, modulation of cigarette smoke-induced oxidative stress and related cellular changes have also been reported to be effected by synthetic molecules. This includes 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, lipid peroxidation and protein carbonylation blockers/inhibitors, such as edaravone and lazaroids/tirilazad, myeloperoxidase inhibitors, as well as specialized pro-resolving mediators/inflammatory resolving lipid mediators, omega-3 fatty acids, vitamin D, and hydrogen sulfide. According to various studies it appears that the administration of multiple antioxidants could be a more effective mode used in the treatment of COPD. In this review, various pharmacological and dietary approaches to enhance lung antioxidant levels and beneficial effects of antioxidant therapeutics in treating or intervening the progression of COPD have been discussed.
慢性阻塞性肺疾病（COPD）的进展和恶化与烟草烟雾/生物燃料引起的氧化和醛/羰基应激密切相关。氧化还原信号转导促炎激酶和转录因子、类固醇耐药性、未折叠蛋白反应、黏液高分泌、细胞外基质重塑、自噬/细胞凋亡、表观遗传改变、细胞衰老/老化、血管内皮功能障碍、自身免疫和骨骼肌功能障碍是 COPD 的一些病理特征。鉴于上述情况，明智的做法是用能够调节抗氧化剂/氧化还原系统的药物或通过提高抗氧化剂的内源性水平来靶向全身和局部氧化应激，以治疗和管理 COPD。各种抗氧化剂的鉴定，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、ergothioneine 和卡巴半胱氨酸赖氨酸盐）、膳食天然产物衍生的多酚和其他化合物（姜黄素、白藜芦醇、绿茶儿茶素、槲皮素、白藜芦醇、越橘、α-硫辛酸、生育三烯酚和 apocynin）已经使调节 COPD 的各种生化方面成为可能。各种研究和临床试验表明，这些抗氧化剂可以解毒自由基和氧化剂，控制氧化还原和谷胱甘肽生物合成基因的表达、染色质重塑，最终控制炎症基因的表达。此外，据报道，合成分子也可以调节香烟烟雾引起的氧化应激和相关的细胞变化。这包括特定的自旋捕获物，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）和超氧化物歧化酶模拟物 M40419、脂质过氧化和蛋白质羰基化抑制剂/抑制剂，如依达拉奉和拉扎罗德/替拉扎德、髓过氧化物酶抑制剂，以及专门的促解决介质/炎症解决脂质介质、ω-3 脂肪酸、维生素 D 和硫化氢。根据各种研究，似乎联合使用多种抗氧化剂可能是治疗 COPD 的更有效模式。在这篇综述中，讨论了增强肺抗氧化水平的各种药理学和饮食方法，以及抗氧化治疗在治疗或干预 COPD 进展中的有益作用。
