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Oxidative Stress


Oxidative stress occurs when the level of oxidants in a system exceed the capacity of the antioxidants to detoxify them, which can lead to oxidative damage to macromolecules, thus harming the cell or tissue.

A free radical is any chemical species capable of independent existence possessing one or more unpaired electrons. Biological free radicals are thus highly unstable molecules that have electrons available to react with various organic substrates.

Many free radicals are the result of naturally occurring processes such as oxygen metabolism and inflammatory processes. For example, when cells use oxygen to generate energy, free radicals are created as a consequence of ATP production by the mitochondria. Exercise can increase the levels of free radicals as can environmental stimuli such as ionizing radiation (from industry, sun exposure, cosmic rays, and medical X-rays), environmental toxins, altered atmospheric conditions (e.g. hypoxia and hyperoxia), ozone and nitrous oxide (primarily from automobile exhaust). Lifestyle stressors such as cigarette smoking and excessive alcohol consumption are also known to affect levels of free radicals. Radical species may combine to form other more damaging or toxic species such as peroxynitrite (O=NOOø), a product of superoxide and nitric oxide radical reaction.

Reactive Oxygen Species (ROS) is a term collectively describing radicals and other non-radical reactive oxygen derivatives. These intermediates may participate in reactions giving rise to free radicals or that are damaging to organic substrates. ROS in living organisms include the following:

Radicals: Hydroxyl (OH-), Superoxide (O2-), Nitric Oxide (NO-), Thyl (RS), Peroxyl (RO2-), Lipid peroxyl (LOO-)

Non-Radicals: Peroxynitrite (ONOO-), Hypochloric acid (HOCl), Hydrogen Peroxide (H2O2), Singlet Oxygen (O2-), Ozone (O3), Lipid peroxide (LOOH)

Reactive Nitrogen Species (RNS) are radical nitrogen-based molecules that can act to facilitate nitrosylation reactions. Reactive Nitrogen Species (RNS) include: Nitrous oxide NO) Nitrosyl cation (NO+), Peroxynitrite (OONOø ), Nitrogen dioxide (NO2¥), Peroxynitrous acid (ONOOH). Dinitrogen trioxide (N2O3), Nitroxyl anion (NOø), Nitrous acid (HNO2), Nitryl chloride (NO2Cl)

Oxidative stress occurs when the generation of ROS in a system exceeds the systemÕs ability to neutralize and eliminate them. The imbalance can result from a lack of antioxidant capacity caused by disturbance in production, distribution, or by an over-abundance of ROS from an environmental or behavioral stressor. If not regulated properly, the excess ROS can damage a cellÕs lipids, protein or DNA, inhibiting normal function. Because of this, oxidative stress has been implicated in a growing list of human diseases as well as in the aging process.

Antioxidants inhibit oxidation by free radicals. There are many types of antioxidants, including:

¥ Detoxification enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione transferase.

¥ Proteins such as glutathione reductase, glucose 6-phosphate dehydrogenase, albumin, transferrin, ceruloplasmin, and metallothionein.

¥ Vitamins such as beta carotene, carotenoids, vitamin C, and vitamin E.

¥ Nutritional supplements including coenzyme Q10, uric acid, cysteine, glutathione, lipoic acid, citric and malic acid, bilirubin, biliverdin, histidine, conjugated linoleic acid and melatonin.




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