Oxidative Stress and Therapeutic Development in Lung Diseases

Abstract

Oxidative stress has many implications in the pathogenesis of lung diseases. In this review, we provide an overview of Reactive Oxygen Species (ROS) and nitrogen (RNS) species and antioxidants, how they relate to normal physiological function and the pathophysiology of different lung diseases, and therapeutic strategies. The production of ROS/RNS from endogenous and exogenous sources is first discussed, followed by antioxidant systems that restore oxidative balance and cellular homeostasis. The contribution of oxidant/antioxidant imbalance in lung disease pathogenesis is also discussed. An overview of therapeutic strategies is provided, such as augmenting NO bioactivity, blocking the production of ROS/RNS and replacement of deficient antioxidants. The limitations of current strategies and failures of clinical trials are then addressed, followed by discussion of novel experimental approaches for the development of improved antioxidant therapies.

Keywords: Antioxidant; Lung disease; Nitric oxide; Oxidative stress; Reactive oxygen species.

Figure 1

Therapeutic approaches to restore redox balance. 1) Augment NO^• bioactivity catalyzed by nitric oxide synthase; 2) Block production of ROS produced by mitochondrial electron transport chain, NADPH oxidase, xanthine oxidase or uncoupled NOS; 3) Scavange toxic oxidants by replacing deficient enzymatic and non-enzymatic antioxidants such as SOD, catalase, GSH, ascorbic acid, tocopherol, and carotenoids.