Oxidative stress



Oxidative stress is caused by an imbalance between the production of DNA.

In humans, oxidative stress is involved in many diseases, such as atherosclerosis, Parkinson's disease and Alzheimer's disease, but it may also be important in prevention of aging by induction of a process named cell signaling. This is dubbed redox signaling.

Chemical and biological effects

In chemical terms, oxidative stress is a large increase (becoming less negative) in the cellular apoptosis, while more intense stresses may cause necrosis.[2]

A particularly destructive aspect of oxidative stress is the production of ATP depletion, preventing controlled apoptotic death and causing the cell to simply fall apart.[4][5]

Oxidant Description
•O2-, superoxide anion One-electron reduction state of O2, formed in many autoxidation reactions and by the electron transport chain. Rather unreactive but can release Fe2+ from iron-sulphur proteins and ferritin. Undergoes dismutation to form H2O2 spontaneously or by enzymatic catalysis and is a precursor for metal-catalyzed •OH formation.
H2O2, hydrogen peroxide Two-electron reduction state, formed by dismutation of •O2- or by direct reduction of O2. Lipid soluble and thus able to diffuse across membranes.
•OH, hydroxyl radical Three-electron reduction state, formed by Fenton reaction and decomposition of peroxynitrite. Extremely reactive, will attack most cellular components
ROOH, organic hydroperoxide Formed by radical reactions with cellular components such as nucleobases.
RO•, alkoxy and ROO•, peroxy radicals Oxygen centred organic radicals. Lipid forms participate in lipid peroxidation reactions. Produced in the presence of oxygen by radical addition to double bonds or hydrogen abstraction.
HOCl, hypochlorous acid Formed from H2O2 by methionine.
OONO-, peroxynitrite Formed in a rapid reaction between •O2- and NO•. Lipid soluble and similar in reactivity to hypochlorous acid. Protonation forms peroxynitrous acid, which can undergo homolytic cleavage to form hydroxyl radical and nitrogen dioxide.

Table adapted from.[6][7][8]

Production and consumption of oxidants

The most important source of reactive oxygen under normal conditions in aerobic organisms is probably the leakage of activated oxygen from mitochondria during normal oxidative respiration.

Other enzymes capable of producing superoxide are xanthine oxidase, NADPH oxidases and cytochromes P450. Hydrogen peroxide is produced by a wide variety of enzymes including several oxidases. Reactive oxygen species play important roles in cell signalling, a process termed redox signaling. Thus, to maintain proper cellular homeostasis, a balance must be struck between reactive oxygen production and consumption.

The best studied cellular antioxidants are the enzymes 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 paraoxonase, glutathione-S transferases, and aldehyde dehydrogenases.

Oxidative stress contributes to tissue injury following irradiation and hyperoxia. It is suspected (though not proven) to be important in 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 vascular endothelium is a precursor to plaque formation. Oxidative stress also plays a role in the ischemic cascade due to oxygen reperfusion injury following hypoxia. This cascade includes both strokes and heart attacks.

Antioxidants as supplements

The use of NXY-059 shows some efficacy in the treatment of stroke.[14]

Oxidative stress (as formulated in Harman's hormesis on a purely hypothetical basis.[18] The situation in mammals is even less clear.[19][20][21] Recent epidemiological findings support the process of mitohormesis, and even suggest that antioxidants may increase disease prevalence in humans.[22]

Metal catalysts

Metals such as manganism with exposure to manganese ores.

Non-metal redox catalysts

Certain organic compounds in addition to metal redox catalyts can also produce reactive oxygen species. One of the most important classes of these are the homocystinuria, as well as atherosclerosis, stroke, and Alzheimers.

Immune defence

The immune system uses the lethal effects of oxidants by making production of oxidizing species a central part of its mechanism of killing pathogens; with activated phagocytes producing both ROS and reactive nitrogen species. These include superoxide (•O2-), nitric oxide (•NO) and their particularly reactive product, peroxynitrite (OONO-).[23] Although the use of these highly reactive compounds in the cytotoxic response of phagocytes causes damage to host tissues, the non-specificity of these oxidants is an advantage since they will damage almost every part of their target cell.[8] This prevents a pathogen from escaping this part of immune response by mutation of a single molecular target.

See also

References

  • Strand, Ray D.; Wallace, Donna K. (2002). What your doctor doesn't know about nutritional medicine may be killing you. Nashville: T. Nelson Publishers. ISBN 0785264868. 
  • Packer, Lester; Colman, Carol (1999). The antioxidant miracle: your complete plan for total health and healing. New York: Wiley. ISBN 0471297682. 
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Oxidative_stress". A list of authors is available in Wikipedia.