Pharmacological and Dietary Antioxidant Therapies for Chronic Obstructive Pulmonary Disease
Pharmacological and Dietary Antioxidant Therapies for Chronic Obstructive Pulmonary Disease
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DOI：
10.2174/0929867311320120004
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发表时间：
2013-04-01
影响因子：
4.1
通讯作者：
Rahman, I.
中科院分区：
文献类型：
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作者：
Biswas, S.;Hwang, J. W.;Rahman, I.
慢性阻塞性肺疾病（COPD）的进展和加重与烟草烟雾/生物质燃料诱导的氧化和醛/羰基应激密切相关。氧化还原信号传导促炎性激酶和转录因子的改变、类固醇抗性、未折叠蛋白应答、粘液分泌过多、细胞外基质重塑、自噬/凋亡、表观遗传变化、细胞衰老/老化、内皮功能障碍、自身免疫和骨骼肌功能障碍是COPD的一些病理学标志。鉴于上述情况，谨慎的做法是用可调节抗氧化剂/氧化还原系统的药剂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。识别各种抗氧化剂，如硫醇分子（谷胱甘肽和粘液溶解药物，如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、麦角硫因和羧半胱氨酸赖氨酸盐）、膳食天然产物衍生的多酚和其它化合物（姜黄素，白藜芦醇，绿色茶儿茶素，槲皮素萝卜硫素，番茄红素，巴西莓，α-硫辛酸，生育三烯酚，和夹竹桃麻素）已经使得调节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，并最终炎症基因的表达。此外，香烟烟雾诱导的氧化应激和相关细胞变化的调制也被报道受到合成分子的影响。这包括特定的自旋陷阱，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阻断剂/抑制剂，如依达拉奉和拉扎罗类化合物/替利扎德，髓过氧化物酶抑制剂，以及专门的促消退介质/炎症消退脂质介质，ω-3脂肪酸维生素D和硫化氢根据各种研究，似乎给予多种抗氧化剂可能是治疗COPD的更有效模式。在这篇综述中，各种药理学和饮食方法，以提高肺抗氧化剂水平和抗氧化剂治疗或干预COPD的进展的有益影响进行了讨论。
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 pro-inflammatory 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 alpha-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.