Pharmacological and Dietary Antioxidant Therapies for Chronic Obstructive Pulmonary Disease

Abstract

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.

Neu-164 and Neu-107, two novel antioxidant and anti-myeloperoxidase compounds, inhibit acute cigarette smoke-induced lung inflammation

“…Thus, there is great interest in the use of antioxidants to prevent and treat smoking-related lung disease. Thiol compounds such as N-acetylcysteine and carbocysteine have been extensively studied, as well as mimetics of superoxide dismutase and glutathione peroxidase, and inhibitors of nitric oxide synthase (4,49).…”

“…Corticosteroids are used to treat acute exacerbations and to provide symptomatic relief in long-term care, but they do not prevent the long-term decline in lung function and are associated with many detrimental side effects (65). Additionally, COPD patients and animals exposed to chronic CS develop steroid resistance due to epigenetic changes to histone acetylation (4,9). This is one of the factors that has prompted the search for novel anti-inflammatory compounds in the treatment of CS-induced lung disease.…”

“…There are numerous studies suggesting antioxidants such as N-acetylcysteine have some benefit in COPD (reviewed in Ref. 4). However, there is also some evidence that dietary antioxidants may promote cancer (5).…”

“…Cysteinyl leukotrienes are potent bronchoconstrictors and also act to increase vascular permeability to cause edema and enhance mucus secretion (36). Leukotriene B 4 , a neutrophil chemoattractant and activator, is increased in exhaled breath condensate from COPD patients (21,27). Inhibitors of the leukotriene pathway were found somewhat effective in several clinical trials in COPD (20,54).…”

Modulatory effects of green tea and aloe vera extracts on experimentally-induced lung fibrosis in rats: histological and immunohistochemical study

“…Some researchers reported that administration of multiple antioxidants could be a more effective mode used in the treatment of obstructive lung diseases [39] and others stated that herb pair which consists of two single herbs presents significantly better pharmacological efficacy than individual herbs because the synergistic interactions between the com-ponents of herbals greatly contribute to the enhancement of their therapeutic efficacy [40]. Contrary to this, group V (green tea and AV group) of the present study revealed thick inter-alveolar, collapsed alveoli, cellular infiltration, dilated congested blood vessels with extravasated RBCs and insignificant decreased (P≤0.05) in collagen fibers accumulation and in caspase-3 expression compared with BLM group.…”