Oxidative stress and antioxidants: Distress or eustress?

Abstract

Oxidative stress, a signal which affects redox balance and induces oxidative modification of biological molecules, may have multiple faces. Reactive oxygen and related species (ROS) protect us from invading xenobiotics and act as physiological redox signaling messenger. The production of ROS is tightly regulated and the reactions are selective. On the other hand, ROS produced by unregulated manner induce random oxidative modification of lipids, proteins, and nucleic acids, which gives rise to deleterious effects and has been implicated in the pathogenesis of many diseases. Thus, ROS may become good stress (eustress) or bad stress (distress). Unsaturated lipids such as linoleic acid (LA), arachidonic acid (AA), and cholesterol, both free and ester forms, are vulnerable to oxidation by multiple oxidants to give diverse products. Lipid hydroperoxides, the major primary product, are toxic per se and may exert deleterious effects by producing reactive secondary products including HNE. We aerobic organisms are protected from lipid oxidation products by inhibiting their production and by inducing adaptive response. It has been shown that multiple antioxidant compounds and enzymes are induced by lipid oxidation products to prepare for subsequent deleterious oxidative stress. The lipid oxidation products produced by random manner may not be physiological signaling messenger, but rather xenobiotics. It has been observed that levels of these products are associated with the onset and progress of diseases such as atherosclerosis. We are protected from oxidative stress by an array of defense system in which multiple antioxidants with diverse functions play their respective roles including reduction of hydrogen peroxide and hydroperoxides, sequestration of metal ions, scavenging of reactive oxidants, repair of damage, and excretion of toxic products. Scavenging of ROS is one of the important functions of antioxidants. It may be noted that the efficacy of scavenging oxidants depends on the nature of oxidants. Further, it is unlikely that antioxidants scavenge such oxidants that act as physiologically important signaling messenger. Interestingly, higher levels of lipid oxidation products produced by peroxyl radicals, peroxynitrite, hypochlorite, 15-lipoxygenase, and singlet oxygen have been found in atherosclerotic lesions than in normal arteries and in plasma of patients than healthy subjects, suggesting that multiple antioxidants are required to inhibit deleterious lipid oxidation in vivo.