Active Oxygen Intermediates–Beneficial or Deleterious? An Introduction

Abstract

Breathing oxygen is, it seems, hazardous to your health. Although life cannot go on without this element, many of the biochemical reactions in which oxygen participates generate oxygen-containing free radicals as byproducts. A free radical is any reactive molecule that contains one or more unpaired electrons (i.e., electrons present singly in atomic or molecular orbitals. An unpaired electron can be associated with almost any atom, and this review concentrates on oxygen-centered inorganic radicals, namely superoxide (O₂ ^-) and the hydroxyl radical (HO·), that are important agents in oxidative stress. The formation of highly reactive oxygen-containing molecular species is a normal consequence of a variety of essential biochemical reactions. The oxygen free radicals (i.e., superoxide anion, hydroxyl radical, singlet oxygen, and hydrogen peroxide) are capable of extensive tissue and endothelial damage. Superoxide anion is the best studied free radical species (1). This free radical may act as a reducing agent donating its electrons or as an oxidizing agent, in which case it is reduced to H₂O₂. The production of the superoxide radical is a double-edged sword. It is beneficial when produced by activated polymorphonuclear leukocytes and other phagocytes as an essential component of their bactericidal activities (2). Nevertheless, if allowed to proceed to excess, the same action may result in tissue damage associated with inflammation (3, 4).

Oxygen free radicals can injure lipids, proteins, and DNA, and thus may contribute to the development or exacerbation of many human diseases, including ischemia-reperfusion injury in heart attacks, organ transplantation, stroke, cancer, and emphysema, in various inflammatory-immune injuries and the disorders of aging, and in several neurodegenerative disorders (5–7). As a result of the potential for free radicals to damage cells and tissues, an intricate system consisting of both enzymes and small molecular weight molecules with antioxidant capabilities has evolved to protect against the adverse effects of free radical reactions. There exists ultimately a critical balance between free radical generation and antioxidant defenses. Some of the protective antioxidants are essential nutrients (e.g., vitamin C, vitamin E, and β-carotene). Some are nutritionally essential minerals incorporated into protective antioxidant enzymes (e.g., zinc, copper, and manganese are required for the activity of the two types of superoxide dismutases, the all important antioxidant enzymes). Selenium, an essential component of glutathione peroxidase, is important in the decomposition of hydrogen peroxide and lipid peroxides.