Approaching reactive species in the frame of their clinical significance: A toxicological appraisal.

Redox biology and toxicology are interrelated fields that have produced valuable evidence regarding the role and clinical significance of reactive species. These issues are analyzed herein by presenting 6 arguments, as follows: Argument 1: There is no direct connection of redox-related pathologies with specific reactive species; Argument 2: The measurement of reactive species concentration is a major challenge due to their very short half lives; Argument 3: There is an interplay between reactive species generation and fundamental biological processes, such as energy metabolism; Argument 4: Reactive species exert beneficial biological action; Argument 5: Reactive species follow the hormesis phenomenon; Argument 6: Oxidative modifications of redox-related molecules are not necessarily interpreted as oxidative damage. We conclude that reactive species do not seem to exert clinical significance, which means that they lack a measurable cause-effect relation with chronic diseases. Unpredictable results could, nevertheless, arise through novel experimental setups applied in the field of toxicology. These are related to the real-life exposure scenario via the regimen of long-term low-dose (far below NOAEL) exposure to mixtures of xenobiotics and can potentially offer perspectives in order to investigate in depth whether or not reactive species can be introduced as clinically significant redox biomarkers.