Reactive oxygen species in disease: Rebuttal of a conventional concept

Abstract

The production of intracellular reactive oxygen species and reactive nitrogen species has long been proposed as leading to the random deleterious modification of macromolecules (i.e., nucleic acids, proteins) with an associated progressive development of the age associated systemic diseases (e.g., diabetes, Parkinson’s disease) as well as contributing to the ageing process.   Superoxide anion (hydrogen peroxide) and nitric oxide (peroxynitrite) comprise regulated intracellular second messenger pro-oxidant systems, with specific sub-cellular locales of production and are essential for the normal function of the metabolome and cellular electro-physiology.  We have posited that the formation of superoxide anion and its metabolic product hydrogen peroxide, and nitric oxide, do not conditionally lead to random damage of macromolecular species such as nucleic acids or proteins.  Under normal physiological conditions their production is intrinsically regulated that is very much consistent with their second messenger purpose of function.   We further propose that the concept of an orally administered small molecule antioxidant as a therapy to abrogate free radical activity (to control oxidative stress) is a chimera.  As such we consider that free radicals are not a major overwhelming player in the development of the chronic diseases or the ageing process.