Evolution of the ¨Oxidative Stress¨ concept: half of a century contributions from the Facultad de Medicina, Montevideo, Uruguay.

Abstract

The following review presents elements in relation to the evolution of the “Oxidative Stress” concept, that span from the first biochemical observations in enzymatic systems to the current therapeutic strategies at the preclinical level. In more than half a century of contributions to the field, it is remarkable the participation of investigators of the Facultad de Medicina, Universidad de la República (Montevideo, Uruguay) from the early days of the research, in particular the Department of Biochemistry, including Visiting Professor John Totter and Professor Eugenio Prodanov. The understanding of the metabolic processes that lead to the formation and detoxification of free radicals and oxidant species, and the development of methodologies for its identification, detection and quantitation has been a central topic of the area. The concept of oxidative stress has developed and evolved to the current definition representing a metabolic imbalance that leads to the alteration of redox signaling and/or an oxidative damage, which in turn facilitates the development and progression of degenerative and inflammatory pathology. Oxidative events are also utilized by immune system cell as a cytotoxic mechanism against invading pathogens. An important advance in the area was the recognition that the metabolism of the free radical nitric oxide was connected with oxidative processes, in particular through its diffusional reaction with superoxide radical to yield peroxynitrite, an unstable and reactive nucleophile and peroxide in biological systems. A better understanding of the intra- and extracellular mechanisms of formation of oxidant species, including the role of mitochondrial dysfunction, as well as the mechanisms of redox signaling, are providing opportunities for developing nutritional and pharmacological strategies for the in vivo modulation of oxidative events associated to pathology. I have selected observations and works with a biochemical emphasis that I consider relevant, and relating and integrating them with contributions carried out from our Faculty in the area of oxidative stress.