Oxidative stress: the paradox of aerobic life

Abstract

The paradox of aerobic life, or the 'Oxygen Paradox', is that higher eukaryotic aerobic organisms cannot exist without oxygen, yet oxygen is inherently dangerous to their existence. This 'dark side' of oxygen relates directly to the fact that each oxygen atom has one unpaired electron in its outer valence shell, and molecular oxygen has two unpaired electrons. Thus atomic oxygen is a free radical and molecular oxygen is a (free) bi-radical. Concerted tetravalent reduction of oxygen by the mitochondrial electron-transport chain, to produce water, is considered to be a relatively safe process; however, the univalent reduction of oxygen generates reactive intermediates. The reductive environment of the cellular milieu provides ample opportunities for oxygen to undergo unscheduled univalent reduction. Thus the superoxide anion radical, hydrogen peroxide and the extremely reactive hydroxyl radical are common products of life in an aerobic environment, and these agents appear to be responsible for oxygen toxicity. To survive in such an unfriendly oxygen environment, living organisms generate--or garner from their surroundings--a variety of water- and lipid-soluble antioxidant compounds. Additionally, a series of antioxidant enzymes, whose role is to intercept and inactivate reactive oxygen intermediates, is synthesized by all known aerobic organisms. Although extremely important, the antioxidant enzymes and compounds are not completely effective in preventing oxidative damage. To deal with the damage that does still occur, a series of damage removal/repair enzymes, for proteins, lipids and DNA, is synthesized. Finally, since oxidative stress levels may vary from time to time, organisms are able to adapt to such fluctuating stresses by inducing the synthesis of antioxidant enzymes and damage removal/repair enzymes. In a perfect world the story would end here; unfortunately, biology is seldom so precise. The reality appears to be that, despite the valiant antioxidant and repair mechanisms described above, oxidative damage remains an inescapable outcome of aerobic existence. In recent years oxidative stress has been implicated in a wide variety of degenerative processes, diseases and syndromes, including the following: mutagenesis, cell transformation and cancer; atherosclerosis, arteriosclerosis, heart attacks, strokes and ischaemia/reperfusion injury; chronic inflammatory diseases, such as rheumatoid arthritis, lupus erythematosus and psoriatic arthritis; acute inflammatory problems, such as wound healing; photo-oxidative stresses to the eye, such as cataract; central-nervous-system disorders, such as certain forms of familial amyotrophic lateral sclerosis, certain glutathione peroxidase-linked adolescent seizures, Parkinson's disease and Alzheimer's dementia; and a wide variety of age-related disorders, perhaps even including factors underlying the aging process itself. Some of these oxidation-linked diseases or disorders can be exacerbated, perhaps even initiated, by numerous environmental pro-oxidants and/or pro-oxid...

Multiscattering-Enhanced Absorption Spectroscopy

“…It is worth noting here that H 2 O 2 plays an important role in biological systems: it acts as a signaling molecule in a broad variety of transduction processes and is a marker for oxidative stress, which is involved in aging but also in various diseases. 55,56 The principle of the bioassay lies in the oxidation of Fe 2+ to Fe 3+ in the presence of H 2 O 2 , which forms a ferric xylenol orange (Fe-XO) complex. The formation of Fe-OX complexes leads to an alteration of the molar absorption coefficient, providing information about the H 2 O 2 concentration present in the solution.…”

Oxidative Stress-Induced Response of Some Endogenous Antioxidants in Schizophrenia

“…Higher eukaryotic aerobic organisms cannot exist without oxygen, yet oxygen is inherently dangerous to their existence [1] as it produces pro-oxidants or reactive oxygen species (ROS) in various metabolic processes [2]. ROS attack macromolecules viz.…”

Development of an in vitro model of excess intracellular reactive oxygen species

“…These data support the proposal that GFP undergoes a reversible oxidationYreduction reaction in the presence of molecular oxygen, and, assuming the proposal is correct, suggests that strong reducing agents would be expected to de-colorize GFP by reducing oxidized Tyr66 which would reduce the chromophore (Hoffman et al 1984;Inouye and Tsuji 1994). One expected consequence of GFP oxidation is the release of H 2 O 2 in 1 : 1 stoichiometry with mature GFP (Davies 1995). The H 2 O 2 by-product created during fluorophore formation might also explain occasions when high-level expression of GFP can be damaging to the cell (Liu et al 1999).…”

“…Certain levels of ROS inevitably escape catalytic conversion, however, and remain in the cell. To this end, antioxidant compounds including vitamin C, vitamin E, ubiquinone, and uric acid may be sacrificed to protect cellular components from oxidative damage (Davies 1995;Tsien 1998;Halliwell and Gutteridge 1999). The delicate balance between enzymatic mechanisms for reducing ROS and intracellular levels of ROS is normally strictly controlled by supplying cells with essential nutrients and by minimizing the effects of substances that stimulate ROS (Murrell et al 1990).…”