Editorial [Hot Topic: Oxidative Stress and Cellular Homeostasis (Executive Editor: Victor M. Victor)]

When there is an imbalance between the production of free radicals (ROS) and the ability of the cell to scavenge them, they accumulate in the cytoplasm, leading to what is known as “oxidative stress”. This situation occurs as a host defence mechanism whose involvement in maintaining homeostasis and/or inducing disease has been widely investigated over the past decade. Cellular targets attacked by ROS include DNA, proteins, membrane lipids, and mitochondria. In particular, free radicals are byproducts of aerobic metabolism, and most cellular ROS are produced due to “leakage” of electrons from the mitochondrial respiratory chain, resulting in an incomplete reduction of molecular oxygen (O2) during oxidative phosphorylation and a production of hydrogen peroxide and the superoxide radical anion. It has been estimated that at O2 physiological levels, 1-3% of the reduced molecular O2 in mitochondria form superoxide. Approximately 85-90% of O2 is used by mitochondria, making the mitochondrion the major site of ROS production. The remaining 10-15% of O2 is used by other cellular oxidative enzymes, including xanthine oxidase in the cytoplasm, and by the cytochrome P450 system in the endoplasmic reticulum, which can also yield ROS. The review articles included in this issue of Current Pharmaceutical Design summarize recent evidence in the field of physiology and pharmacology. In the first article [1], the author discusses the role of oxidative processes in atherosclerosis and the cardiovascular diseases (CVD) that can arise as a result. Atherosclerosis represents a state of heightened oxidative stress characterized by lipid and protein oxidation in the vascular wall. As an expert in the field, the author describes an overproduction of ROS under pathophysiologic conditions, and these ROS form an integral part of the development of CVD, and in particular atherosclerosis. Endothelial dysfunction, characterized by a diminution of nitric oxide (NO) bioactivity, occurs early on in the development of atherosclerosis, and determines future vascular complications. Although the molecular mechanisms responsible for mitochondria-mediated disease processes are not clear, oxidative stress seems to play an important role. This review provides a summary of the cellular metabolism of ROS and its role in pathophysiological processes such as atherosclerosis. In addition, the author describes currently available antioxidants and possible reasons for their efficacy and inefficacy in ameliorating oxidative stress-mediated diseases. The outstanding review by De la Fuente et al. [2] focuses on the aging process as one of the best examples of the effects of deterioration of homeostasis, describing how aging is accompanied by an impairment of physiological systems such as the immune system. The authors propose an integrative theory of aging. In accordance with this oxidation-mitochondrial theory, they have observed that the age-related changes of immune functions are based on a situation of oxidative and inflammatory stress among whose intracellular mechanisms is the activation of the NFkB in the immune cells. The authors present a clear argument for why several functions of the immune cells are good markers of biological age and predictors of longevity. Based on the above, they propose a theory of oxidation-inflammation as the main cause of aging. Accordingly, the chronic oxidative stress that appears with age affects all cells, and especially those of the regulatory systems, such as the nervous, endocrine and immune systems, and the communication between them. This prevents an adequate homeostasis, and therefore is an obstacle to the preservation of health. The authors also propose a key involvement of the immune system in the aging process of the organism, specifically in the rate of aging, based on the relation between the redox state and functional capacity of the immune cells and the longevity of individuals. Finally, they affirm that adequate amounts of antioxidants in the diet improve immune functions, thereby decreasing oxidative stress, and consequently increasing the longevity of subjects.