Pharmacological antioxidant strategies as therapeutic interventions for COPD

AbstractCigarette/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

Strategies to decrease ongoing oxidant burden in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and morbidity globally, and its development is mainly associated with tobacco/biomass smoke-induced oxidative stress. Hence, targeting systemic and local oxidative stress with agents that can balance the antioxidant/redox system can be expected to be useful in the treatment of COPD. Preclinical and clinical trials have revealed that antioxidants/redox modulators can detoxify free radicals and oxidants, control expression of redox and glutathione biosynthesis genes, chromatin remodeling and inflammatory gene expression; and are especially useful in preventing COPD exacerbations. In this review, various novel approaches and problems associated with these approaches in COPD are reviewed