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.

The dilemma of oxidative stress personified by the diprosopus 8-iso-prostaglandin F2α and prostaglandin F2α

“…The scientific research area of oxidative stress is highly challenging, and the role attributed to free radicals in the development of chronic diseases and aging process is overestimated (10). Many of the biomarkers being presently used to quantify oxidative stress, including 8-iso-PGF 2α and MDA, can be generated both by enzymes and free radicals or by nonradical reactive oxygen/nitrogen species, which, in turn, are produced both by enzymes and chemicals especially including transition metal ions.…”

Does Oxidative Stress Change During Orthotopic Liver Transplantation?

“…However, in plasma samples of the same patients, we found elevated 15(S)-8-iso-PGF 2α , 3-nitrotyrosine, and 3-nitrotyrosinoalbumin concentrations (2, 3), suggesting elevated oxidative and nitrosative stress in end-stage liver disease. Because of the duality of oxidative stress and for many other reasons, notably including analytical shortcomings and pitfalls (1), the conventional concept of oxidative stress in human disease has been questioned (1,11).…”