Reactive Species and Mechanisms of Cell Injury

In this article, we review established evidence for the pathophysiological role of the main reactive radical and nonradical species, namely, reactive oxygen species (ROS) and nitric oxide and its derived nitrogen species. ROS are generated endogenously as a by-product of the process of mitochondrial electron transfer, that is, of cellular respiration, and in specific cell types under defined conditions, such as inflammation, by NADPH oxidases. ROS may be generated also via interactions with xenobiotic compounds. Nitric oxide (NO) is generated endogenously by NO synthases, enzymes expressed by most cell types. At physiological concentrations, ROS and NO act as physiological mediators; when produced at high levels such that they overcome the cellular antioxidant defense system, they lead to oxidative stress, via oxidation and nitrosylation, respectively, of cysteine residues on proteins. These oxidative modifications result in changes in structure and/or function of cellular proteins and also damage lipids and/or DNA. These damaging effects of radical species contribute to carcinogenesis, neurodegeneration, atherosclerosis, diabetes, and aging.