Oxidative Stress and Antioxidant Defenses in Biology

The ground-state of molecular oxygen, O, is essential to many 2 indispensible metabolic processes of all aerobic life forms ranging from prokaryotes, protists, plants, and fungi to animals. Research by mammalian toxicologists and clinicians has unravelled persua- sive evidence that O dependence imposes universal toxicity to all 2 aerobic life processes. The basis of this paradox is that one-electron reduction of O2 generates the superoxide anion free radical, 0;-, from numerous biological sources; for example, redox-active autoxidizable molecules such as catecholamines, oxidoreductases, and subcellular organelles such as mitochondria, endoplasmic retiC- ulum (microsomes), nuclei, and chloroplasts. Oxygen is also acti- vated in biologically relevant photosensitizing reactions to highly re- active singlet oxygen, 10, 2 In all biological systems, 0;- undergoes further reduction to H 0 2 2 via Fenton reaction to the hydroxyl radical, -OH. These, and some other forms of activated O, constitute reactive oxygen species (ROS) 2 and/or metabolites (ROM). Both OH and 10 are the most reactive 2 forms of ROS known and among their deleterious reactions are ox- idation of proteins, DNA, steroidal compounds, and peroxidation of the cell membranes unsaturated lipids to form unstable hydro- peroxides. Their many breakdown products include malondialde- hyde and hydroxynonenals that are themselves highly reactive and threaten cellular integrity and function. More importantly, they de- compose to free radicals that can continue to propagate the vicious lipid peroxidation chain reaction. This is the so-called endogenous oxidative stress with which all aerobic organisms must cope.