Reactive Oxygen Species and Natural Antioxidants: A Review

REACTIVE OXYGEN SPECIES & FREE RADICALS It is ironic that oxygen, an element indispensable for life [1], under certain situations has deleterious effects on human body [2]). Most of the potentially harmful effects of oxygen are due to the formation and activity of number of chemical compounds known as ROS, which have a tendency to donate oxygen to other substances. The causes of the poisonous properties of oxygen were obscure prior to the publication of Gershman’s free radical theory of oxygen toxicity in 1954, which states that the toxicity of oxygen is due to partially reduced forms of oxygen [3]. Oxygen free radicals or, more generally, reactive oxygen species (ROS), as well as reactive nitrogen species (RNS) are products of normal cellular metabolism. Free radicals can be defined as molecules or molecular fragments containing one or more unpaired electrons in atomic or molecular orbits [4]. This unpaired electron(s) usually give a considerable degree of reactivity to the free radical. Radicals derived from oxygen represent the most important class of radical species generated in living systems [5]. Molecular oxygen (dioxygen) has a unique electronic configuration and is itself a radical. The addition of one electron to dioxygen forms the superoxide anion radical(O2-)[5]. Superoxide anion, arising either through metabolic processes or following oxygen “activation” by physical irradiation is considered the “primary” ROS, and can further interact with other molecules to generate “secondary” ROS, either directly or prevalently through enzyme or metal catalyzed processes [6]. The presence of an unpaired electron in an atomic orbital giving a thorough definition to free radical, results in certain common properties that are shared by most radicals. Many radicals are unstable and highly reactive, that can either donate an electron to, or accept an electron from other molecules, therefore behaving as oxidants or reductants [7]. Natural process of generation of ROS Free radicals and other ROS are derived from normal essential metabolic processes in the human body. Due to the continuous process of both enzymatic and non-enzymatic reactions free radical formation occurs continuously in the cells. Enzymatic reactions, which serve as source of free radicals, include those involved in the respiratory chain, in phagocytosis, in prostaglandin synthesis and in the cytochrome P-450 system[8]. Free radicals can also be formed in nonenzymatic reactions of oxygen with organic compounds as well as those initiated by ionizing reactions. The research of free radicals in biological systems and their enzymatic roles were explored in 1969 when Mc Cord and Fridovich discovered the enzyme superoxide dismutase (SOD), and thus provided convincing evidence about the importance of free radicals in living systems [9]. Further explorations date from 1977, when Mittal and Murad provided evidence that the hydroxyl radicals, OH, stimulate activation of guanylate cyclase and formation of the “second messenger” cyclic guanosine monophosphate (cGMP) [10]. Since then a large body of evidence has been accumulated that living systems have not only adapted to a coexistence with free radicals but have developed various mechanisms for the advantageous use of free radicals in various physiological functions. A B R