Oxidative stress
Oxidative stress is a medical term for damage to animal or plant cells (and thereby the organs and tissues composed of those cells) caused by reactive oxygen species, which include (but are not limited to) superoxide, singlet oxygen, peroxynitrite or hydrogen peroxide. It is defined as an imbalance between free radicals and antioxidants, with the former prevailing. Superoxide is produced deleteriously by 1-electron transfers in the mitochondrial electron transfer chain. Other enzymes capable of producing superoxide are xanthine oxidase, NADPH oxidases and cytochrome P450(s). Hydrogen peroxide is produced by a wide variety of enzymes including monoxygenases and oxidases. In Redox signaling reactive oxygen species play a role in cell signalling.
The best studied cellular antioxidants are the enzymes Superoxide dismutase (SOD), Catalase, and glutathione peroxidase. Less well studied (but probably just as important) enzymatic antioxidants are the Peroxiredoxins and the recently discovered sulfiredoxin. Other enzymes that have antioxidant properties (though this is not their primary role) include Paraxonase, Glutathione-S transferases, and aldehyde dehydrogenases.
Oxidative stress contributes to tissue injury following irradiation and hyperoxia. It is suspected (though not proven) to be a cause of neurodegenerative diseases including Lou Gehrig's disease (aka MND or ALS), Parkinson's disease, Alzheimer's disease, and Huntington's disease. Oxidative stress is thought to be linked to certain cardiovascular disease, since oxidation of LDL in the endothelium is a precursor to plaque formation. Oxidative stress also plays a role in the ischemic cascade due to oxygen deprivation. This includes Stroke and Heart attack.
The use of antioxidants in this area has shown numbers of positive results although some treatment is controversial. E.g., clinical trials with the antioxidant vitamin E have failed to demonstrate a clear beneficial effect, though it was noted that some study used synthetic vitamin E and used it as a single "bullet" in high-risk group (e.g. smokers)[citation needed]. In a high-risk group like smokers, the use of vitamin E alone without supplemented by other types of antioxidant, e.g. vitamin C and alpha-lipoic acid, can be harmful. In this high-risk group, when neutralizing free radical, there is high chance for vitamin E to be pro-oxidant. Only vitamin C and alpha-lipoic acid can regenerate back the vitamin E. However, vegetables rich in vitamin E are beneficial to neurodegenerative disease. Epidemiological evidence suggests that vitamin E supplementation decreases the incidence of ALS and Alzheimer's. Similarly, AstraZeneca's radical scavenging nitrone drug NXY-059 shows some efficacy in the treatment of stroke.
Oxidative stress (as formulated in Harman's free radical theory of aging) is also thought to contribute to the aging process. While there is rather strong evidence to support this idea in the model organism Drosophila melanogaster, the evidence in mammals is contradictory.
Metal catalysts
Metals such as iron, copper, chromium, vanadium and cobalt are capable of redox cycling in which a single electron may be accepted or donated by the metal. This action catalyzes reactions that produce reactive radicals and can produce reactive oxygen species such as hydroxyl radical in reactions like Fenton's reaction. The hydroxyl radical then can lead to modifications of amino acids (e.g. meta-tyrosine and ortho-tyrosine formation from phenylalanine), carbohydrates, initiate lipid peroxidation. Most enzymes that produce reactive oxygen species contain one of these metals. The presence of such metals in biological systems in an unsequestered form (not in an enzyme or other protein) can significantly increase the level of oxidative stress.
See also
References
- Current Medicinal Chemistry, Volume 12, Number 10, May 2005, pp. 1161-1208(48) Metals, Toxicity and Oxidative Stress
- Strand, What Your Doctor Doesn't Know about Nutritional Medicine May Be Killing You.
- Parker, The Antioxidant Miracle.