Oxygen toxicity and reactive oxygen species: the devil is in the details

Abstract

Reactive oxygen species (ROS) serve as cell signaling molecules for normal biologic processes. However, the generation of ROS can also provoke damage to multiple cellular organelles and processes, which can ultimately disrupt normal physiology. An imbalance between the production of ROS and the antioxidant defenses that protect cells has been implicated in the pathogenesis of a variety of diseases, such as cancer, asthma, pulmonary hypertension, and retinopathy. The nature of the injury will ultimately depend on specific molecular interactions, cellular locations, and timing of the insult. This review will outline the origins of endogenous and exogenously generated ROS. The molecular, cellular, pathologic, and physiologic targets will then be discussed with a particular emphasis on aspects relevant to child development. Finally, antioxidant defenses that scavenge ROS and mitigate associated toxicities will be presented, with a discussion of potential therapeutic approaches for the prevention and/or treatment of human diseases using enzymatic and nonenzymatic antioxidants.