Introduction

The fi rst reports of the independent existence of free radicals appeared in the early 20th century. Until the mid 1980s, studies of free radicals, were mainly restricted to chemical processes involving industrial research related to rubber, plastic, oil, paint and food. However few addressed biological and medical studies. In fact, until the late 1960s, one could not imagine the possibility of generating free radicals in living organisms. The participation of these highly reactive chemical species in biological processes and diseases began to be evident in 1968 with the discovery of an enzyme called eritrocuprein. It was later renamed superoxide dismutase, having but one function which was to participate in the dismutation reaction of the superoxide anion. During the 1970s and 1980s, the concept of oxidative stress was introduced, and since then medical research has had an explosive growth in this area. Also during this period, the anion superoxide production by macrophages and the generation of the hydroxyl radical as a major factor in the harmful effects of these species in humans was indentifi ed for the fi rst time. Most of these studies reported injurious effects being promoted by these species on cells and tissues. Meanwhile, there was also the discovery of nitric oxide as a vascular relaxing factor and its involvement in damaging processes associated with the formation of peroxynitrite by reaction with superoxide anion. The number of diseases, partially or wholly associated to the action of free radicals, increased dramatically during this period. Today, however, it is rare to fi nd a disease in which free radicals are not involved in its mechanism. Although the participation of radicals as a harmful agent is extremely important in cell damage and disease, a new chapter in the history of free radicals unfolded in the 1990s with the discovery of the nuclear factor kB (NF-kB) activation by reactive oxygen species. The involvement of reactive oxygen and nitrogen species as a regulatory or a trigger in the signal transduction process became the focus of much research in the 1990s and expanded substantially in the next decade. Today, it occupies an important place in the complex network of cellular signaling. Recently, a new fi eld of research has emerged on these species, which is signaling and gene modulation caused by these species in the mechanisms of cell damage and disease, i.e., in addition to the direct action of free radicals in biological

structures, its involvement in cell damage by triggering and signaling gene expression. The muscle atrophy that occurs in a number of diseases such as cancer and arthritis, which leads to cachexia, is a good example. The reactive oxygen and nitrogen species associated with muscle mass loss, through the signaling pathways of proteolytic genes, was demonstrated over the past fi ve years. Forthcoming research on the involvement of free radicals in the mechanisms of cell injury and modulation of gene expression leading to diseases suggests a paradigm shift. First, the specifi c action of different lipid peroxides and aldehydes formed in the peroxidative process should replace the current idea of nonspecifi c action of free radicals or oxidative stress as a single event measured by general parameters. Such compounds have different and sometimes antagonistic actions with respect to gene expression signals. Another aspect to be considered is the lipid peroxidation, modifi cation of proteins and nucleic acids from the action of free radicals, as a protective mechanism in the context of certain diseases. Cancer, whose determinant of promotion, proliferation and cell death will depend on the cell environment is a good example. In this sense, more important than knowing if a tissue is suffering from oxidative damage or not, is the evaluation of the profi le of compounds formed from this process, particularly those related to lipid peroxidation, known to be involved in the signaling of genes linked to cell proliferation, apoptosis and necrosis. Thus, future studies of the involvement of free radicals and oxidative stress in mechanisms of disease will have to be much more elaborate, taking into account the myriad of compounds formed in the oxidation of cells and tissues, not to mention its specifi c targets. This book examines the involvement of reactive oxygen species and oxidative stress in different diseases. It is divided into fi ve main topics, an introductory section and four parts specifi cally dedicated to the study of the role of oxidative stress in chronic diseases: metabolic diseases, transmissible diseases, autoimmune and neurodegenerative diseases, cancer and cachexia.