Abstract
Free radicals are chemical species (atoms, molecules, or ions) containing one or more unpaired electrons in their external orbitals and generally display a remarkable reactivity. The evidence of their existence was obtained only at the beginning of the 20th century. Chemists gradually ascertained the involvement of free radicals in organic reactions and, in the middle of the 20th century, their production in biological systems. For several decades, free radicals were thought to cause exclusively damaging effects . This idea was mainly supported by the finding that oxygen free radicals readily react with all biological macromolecules inducing their oxidative modification and loss of function. Moreover, evidence was obtained that when, in the living organism, free radicals are not neutralized by systems of biochemical defences, many pathological conditions develop. However, after some time, it became clear that the living systems not only had adapted to the coexistence with free radicals but also developed methods to turn these toxic substances to their advantage by using them in critical physiological processes. Therefore, free radicals play a dual role in living systems: they are toxic by-products of aerobic metabolism, causing oxidative damage and tissue dysfunction, and serve as molecular signals activating beneficial stress responses. This discovery also changed the way we consider antioxidants. Their use is usually regarded as helpful to counteract the damaging effects of free radicals but sometimes is harmful as it can block adaptive responses induced by low levels of radicals.
Highlights
The term “radical” was first introduced by Guyton de Morveau in 1786 and later used by Gay-Lussac, Liebig, and Berzelius to indicate groups of atoms which were found unchanged in many substances
The path, which has led to the onset and acceptance by the scientific community of the idea that free radicals are continuously formed in the cell as collateral products of normal metabolic reactions, can be initiated by the discovery of the mechanisms underlying the effects of oxygen toxicity and ionizing radiation
NO⋅ worked as a signalling molecule mediating vasodilation when produced in low concentrations by the constitutive isoform of nitric oxide synthase in vascular endothelial cells [276]. It worked as a source of highly toxic oxidants, such as peroxynitrite and nitrogen dioxide (NO2), utilized for microbicidal killing when produced in high concentrations by iNOS in macrophages [277]. These results suggested that the cellular levels of reactive species determine the shift from their beneficial to harmful effects, the concentrations to which this shift happens were and still remain generally unknown today
Summary
The term “radical” was first introduced by Guyton de Morveau in 1786 and later used by Gay-Lussac, Liebig, and Berzelius to indicate groups of atoms which were found unchanged in many substances (see Solov’ev [1]). The first reaction involving free radicals was that of Fenton in 1894 [3]. He noted that when to a small amount of a tartaric acid solution a drop of diluted solution of ferrous sulphate was added, followed by a drop of hydrogen peroxide and an excess of caustic alkali, a light violet colour was obtained. Free radicals were not known at that time, and only three decades later, the Oxidative Medicine and Cellular Longevity. The Fenton reaction plays a very important role in free radical biology and medicine. The path taken to recognize the possibility of the independent existence of free radicals and their fundamental importance for living systems has been long and not without obstacles. This review is aimed at retracing this path by highlighting the steps that have made a fundamental contribution to understanding the role played by free radicals in biological systems (Table 1)
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