Citizendia
Your Ad Here

Oxidative stress is caused by an imbalance between the production of reactive oxygen and a biological system's ability to readily detoxify the reactive intermediates or easily repair the resulting damage. Reactive oxygen species (ROS are ions or very small molecules that include Oxygen Ions free radicals, and Peroxides both inorganic and All forms of life maintain a reducing environment within their cells. Life is a state that distinguishes Organisms from non-living objects such as non-life and dead organisms being manifested by growth through Metabolism Redox (shorthand for reduction-oxidation reaction describes all Chemical reactions in which atoms have their Oxidation number ( Oxidation state This reducing environment is preserved by enzymes that maintain the reduced state through a constant input of metabolic energy. Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins Disturbances in this normal redox state can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids, and DNA. A peroxide is a compound containing an Oxygen -oxygen single bond. In Chemistry, radicals (often referred to as free radicals) are atoms molecules or ions with Unpaired electrons on an otherwise Open shell Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl Lipids are broadly defined as any fat- Soluble ( lipophilic) naturally-occurring Molecule, such as fats oils waxes cholesterol sterols fat-soluble Deoxyribonucleic acid ( DNA) is a Nucleic acid that contains the genetic instructions used in the development and functioning of all known

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 mitohormesis. Atherosclerosis is a Disease affecting arterial Blood vessels It is a chronic inflammatory response in the walls of arteries in large part due to the accumulation Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the Central nervous system that often impairs the sufferer's Alzheimer's disease ( AD) also called Alzheimer disease or simply Alzheimer's, is the most common form of Dementia. Ageing or aging (American English is the accumulation of changes in an organism Hormesis (from Hellenistic Greek hórmēsis "rapid motion eagerness" from ancient Greek hormáein "to set in motion impel urge on" is Reactive oxygen species can be beneficial, as they are used by the immune system as a way to attack and kill pathogens. Reactive oxygen species (ROS are ions or very small molecules that include Oxygen Ions free radicals, and Peroxides both inorganic and An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor A pathogen (from Greek πάθος pathos "suffering passion" and γἰγνομαι (γεν- gignomai (gen- "I give birth to" infectious Reactive oxygen species are also used in cell signaling. Cell signaling is part of a Complex system of Communication that governs basic cellular activities and coordinates cell actions This is dubbed redox signaling. Redox signaling is the process wherein Free radicals, Reactive oxygen species (ROS and other electronically-activated species act as messengers in biological systems

Contents

Chemical and biological effects

In chemical terms, oxidative stress is a large increase (becoming less negative) in the cellular reduction potential, or a large decrease in the reducing capacity of the cellular redox couples, such as glutathione. In Electrochemistry, the standard electrode potential, abbreviated Eo E0 or EO (with a superscript Plimsoll character pronounced Glutathione ( GSH) is a Tripeptide. It contains an unusual Peptide linkage between the amine group of Cysteine and the Carboxyl [1] The effects of oxidative stress depend upon the size of these changes, with a cell being able to overcome small perturbations and regain its original state. However, more severe oxidative stress can cause cell death and even moderate oxidation can trigger apoptosis, while more intense stresses may cause necrosis. Necrosis (in Greek Νεκρός = "dead" is the name given to unnatural Death of cells and living tissue. [2]

A particularly destructive aspect of oxidative stress is the production of reactive oxygen species, which include free radicals and peroxides. Reactive oxygen species (ROS are ions or very small molecules that include Oxygen Ions free radicals, and Peroxides both inorganic and In Chemistry, radicals (often referred to as free radicals) are atoms molecules or ions with Unpaired electrons on an otherwise Open shell A peroxide is a compound containing an Oxygen -oxygen single bond. Some of the less reactive of these species (such as superoxide) can be converted by oxidoreduction reactions with transition metals or other redox cycling compounds (including quinones) into more aggressive radical species that can cause extensive cellular damage. Superoxide is the Anion O2&minus It is important as the product of the one-electron reduction of Dioxygen, which occurs widely in nature Redox (shorthand for reduction-oxidation reaction describes all Chemical reactions in which atoms have their Oxidation number ( Oxidation state In Chemistry, the term transition metal (sometimes also called a transition element) has two possible meanings It commonly refers to any element in "DDQ" redirects here DDQ is also the former callsign of a TV station in Toowoomba Queensland Australia [3] Most of these oxygen-derived species are produced at a low level by normal aerobic metabolism and the damage they cause to cells is constantly repaired. Cellular respiration is the set of the metabolic reactions and processes that take place in Organisms cells to convert biochemical energy from However, under the severe levels of oxidative stress that cause necrosis, the damage causes ATP depletion, preventing controlled apoptotic death and causing the cell to simply fall apart. Adenosine-5'-triphosphate ( ATP) is a multifunctional Nucleotide that is most important as a " molecular currency" of intracellular Energy [4][5]

Oxidant Description
•O2-, superoxide anion One-electron reduction state of O2, formed in many autoxidation reactions and by the electron transport chain. Superoxide is the Anion O2&minus It is important as the product of the one-electron reduction of Dioxygen, which occurs widely in nature An electron transport chain couples a chemical reaction between an electron donor (such as NADH) and an electron acceptor (such as O2) to the transfer Rather unreactive but can release Fe2+ from iron-sulfur proteins and ferritin. Ferritin is a Globular protein complex consisting of 24 protein subunits and is the main intracellular iron storage protein in both Prokaryotes 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. Hydrogen peroxide (H2O2 is a very pale blue liquid which appears colorless in a dilute solution slightly more Viscous than water Lipid soluble and thus able to diffuse across membranes.
•OH, hydroxyl radical Three-electron reduction state, formed by Fenton reaction and decomposition of peroxynitrite. Hydroxyl in Chemistry describes a molecule consisting of an Oxygen atom and a Hydrogen atom joined by a Covalent bond. Fenton's reagent is a solution of Hydrogen peroxide and an Iron Catalyst that is used to Oxidize Contaminants or Waste waters Peroxynitrite is the Anion with the formula ONOO− It is an unstable "valence isomer" of Nitrate, NO3− which has the Extremely reactive, will attack most cellular components
ROOH, organic hydroperoxide Formed by radical reactions with cellular components such as lipids and nucleobases. A peroxide is a compound containing an Oxygen -oxygen single bond. Lipids are broadly defined as any fat- Soluble ( lipophilic) naturally-occurring Molecule, such as fats oils waxes cholesterol sterols fat-soluble Structure The "skeleton" of adenine
RO•, alkoxy and ROO•, peroxy radicals Oxygen centred organic radicals. Lipid forms participate in lipid peroxidation reactions. Lipid peroxidation refers to the oxidative degradation of Lipids It is the process whereby free radicals "steal" electrons from the lipids in Produced in the presence of oxygen by radical addition to double bonds or hydrogen abstraction.
HOCl, hypochlorous acid Formed from H2O2 by myeloperoxidase. Hypochlorous acid ( IUPAC name chloric(I acid) is a weak Acid with the Chemical formula HOCl Myeloperoxidase (MPO is a Peroxidase Enzyme ( most abundantly present in Neutrophil granulocytes (a subtype of White blood cells. Lipid soluble and highly reactive. Will readily oxidize protein constituents, including thiol groups, amino groups and methionine. In Organic chemistry, a thiol is a compound that contains the functional group composed of a Sulfur atom and a Hydrogen atom (-SH Amines are Organic compounds and Functional groups that contain a basic Nitrogen Atom with a Lone pair. Methionine ( abbreviated as Met or M) is an α- Amino acid with the Chemical formula HO2CCH(NH2CH2CH2SCH3
ONOO-, peroxynitrite Formed in a rapid reaction between •O2- and NO•. Peroxynitrite is the Anion with the formula ONOO− It is an unstable "valence isomer" of Nitrate, NO3− which has the 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. Nitrogen dioxide is the Chemical compound with the formula N[[Oxygen O]]2

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. In Cell biology, a mitochondrion (plural mitochondria) is a membrane-enclosed Organelle found in most eukaryotic cells.

Other enzymes capable of producing superoxide are xanthine oxidase, NADPH oxidases and cytochromes P450. The Enzyme xanthine oxidase, or XO, (bovine milk enzyme is,) catalyzes the Oxidation of Hypoxanthine to Xanthine and can further Cytochrome P450 (abbreviated CYP, P450, infrequently CYP450) is a very large and diverse superfamily of Hemoproteins found in all Domains 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. Redox signaling is the process wherein Free radicals, Reactive oxygen species (ROS and other electronically-activated species act as messengers in biological systems Thus, to maintain proper cellular homeostasis, a balance must be struck between reactive oxygen production and consumption. Homeostasis (from Greek: ὅμος hómos, "equal" and ιστημι istēmi, "to stand" lit

The best studied cellular antioxidants are the enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase. The enzyme superoxide dismutase ( SOD,) catalyzes the Dismutation of Superoxide into Oxygen and Hydrogen peroxide. Catalase is a common Enzyme found in nearly all living organisms where it functions to catalyze the decomposition of Hydrogen peroxide to Glutathione peroxidase () is the general name of an Enzyme family with Peroxidase activity whose main biological role is to protect the organism from oxidative damage Less well studied (but probably just as important) enzymatic antioxidants are the peroxiredoxins and the recently discovered sulfiredoxin. In Enzymology, a sulfiredoxin ( is an Enzyme that catalyzes the Chemical reaction peroxiredoxin-(S-hydroxy-S-oxocysteine + 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. Oxygen toxicity or oxygen toxicity syndrome (also known as the " Paul Bert effect" or the "Lorrain Smith effect" describes harmful effects caused 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. Neurodegenerative Disease ( Greek νέυρο- néuro-, "nerval" and Latin dēgenerāre, "to decline" or "to The motor neurone diseases (or motor neuron diseases) (MND are a group of progressive neurological disorders that destroy Motor neurones the cells that control voluntary Parkinson's disease (also known as Parkinson disease or PD) is a degenerative disorder of the Central nervous system that often impairs the sufferer's Alzheimer's disease ( AD) also called Alzheimer disease or simply Alzheimer's, is the most common form of Dementia. Huntington's disease, also called Huntington's chorea, chorea major, or HD, is a genetic neurological disorder characterized after 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. Cardiovascular disease or cardiovascular diseases refers to the class of diseases that involve the Heart or Blood vessels ( arteries and Low-density lipoprotein ( LDL) is a type of Lipoprotein that transports Cholesterol and Triglycerides from the Liver to peripheral The endothelium is the thin layer of cells that line the interior surface of Blood vessels forming an interface between circulating Blood in the In Pathology, an atheroma (plural atheromata is an accumulation and swelling (-oma in Artery walls that is made up of cells (mostly Macrophage cells Oxidative stress also plays a role in the ischemic cascade due to oxygen reperfusion injury following hypoxia. The ischemic (ischaemic cascade is a series of biochemical reactions that take place in the Brain and other aerobic tissues after seconds to minutes of Ischemia (inadequate Chronic Hypoxia is a pathological condition in which the body as a whole ( generalized hypoxia) or region of the body ( tissue hypoxia) is deprived of adequate This cascade includes both strokes and heart attacks. Myocardial infarction ( MI or AMI for acute myocardial infarction) also known as a heart attack, occurs when the blood supply

Antioxidants as supplements

The use of antioxidants to prevent disease is controversial. An antioxidant is a Molecule capable of slowing or preventing the oxidation of other molecules [9] In a high-risk group like smokers, high doses of beta carotene increased the rate of lung cancer. The term carotene is used for several related substances having the formula C40H56 [10] In less high-risk groups, the use of vitamin E appears to reduce the risk of heart disease. Heart disease is an Umbrella term for a variety for different diseases affecting the Heart. [11] In other diseases, such as Alzheimer's, the evidence on vitamin E supplementation is mixed. [12][13] However, AstraZeneca's radical scavenging nitrone drug NXY-059 shows some efficacy in the treatment of stroke. AstraZeneca PLC (,) is a large Anglo-Swedish Pharmaceutical company formed on 6 April 1999 by the remerger of Swedish Astra AB A nitrone is the N-oxide of an Imine and a Functional group in Organic chemistry. Disufenton sodium ( NXY-059) is the disulfonyl derivative of the neuroprotective spintrap Phenylbutynitrone or "PBN" [14]

Oxidative stress (as formulated in Harman's free radical theory of aging) is also thought to contribute to the aging process. Denham Harman (born February 14, 1916) MD PhD FACP FAAA biogerontologist is Professor Emeritus at the University of Nebraska Medical The free-radical theory of aging states that organisms age because cells accumulate Free radical damage over Time. While there is good evidence to support this idea in model organisms such as Drosophila melanogaster and Caenorhabditis elegans,[15][16] recent evidence from Michael Ristow's laboratory suggests that oxidative stress may also promote life expectancy of Caenorhabditis elegans by inducing a secondary response to initially increased levels of reactive oxygen species. Drosophila melanogaster (from the Greek for black-bellied dew-lover) is a two-winged insect that belongs to the Diptera, the order Caenorhabditis elegans (ˌsiːnoʊræbˈdaɪtɪs ˈɛlɪgænz is a free-living Nematode (roundworm about 1  mm in length which Michael Ristow (b April 24, 1967) is a German Medical researcher who has published influential articles on the metabolic basis of human Caenorhabditis elegans (ˌsiːnoʊræbˈdaɪtɪs ˈɛlɪgænz is a free-living Nematode (roundworm about 1  mm in length which [17] This process was previously named mitohormesis or mitochondrial hormesis on a purely hypothetical basis. Hormesis (from Hellenistic Greek hórmēsis "rapid motion eagerness" from ancient Greek hormáein "to set in motion impel urge on" is In Cell biology, a mitochondrion (plural mitochondria) is a membrane-enclosed Organelle found in most eukaryotic cells. Hormesis (from Hellenistic Greek hórmēsis "rapid motion eagerness" from ancient Greek hormáein "to set in motion impel urge on" is [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. Epidemiology is the study of factors affecting the Health and Illness of populations and serves as the foundation and Logic of interventions made in the Hormesis (from Hellenistic Greek hórmēsis "rapid motion eagerness" from ancient Greek hormáein "to set in motion impel urge on" is In Epidemiology, the prevalence of a Disease in a Statistical population is defined as the total number of cases of the disease in the population at a given [22]

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. Iron (ˈаɪɚn is a Chemical element with the symbol Fe (ferrum and Atomic number 26 Copper (ˈkɒpɚ is a Chemical element with the symbol Cu (cuprum and Atomic number 29 Chromium (ˈkroʊmiəm is a Chemical element which has the symbol Cr and Atomic number 24 Vanadium (vəˈneɪdiəm is a Chemical element that has the symbol V and Atomic number 23 Cobalt (ˈkoʊbɒlt is a hard lustrous silver-grey Metal, a Chemical element with symbol Co. Redox (shorthand for reduction-oxidation reaction describes all Chemical reactions in which atoms have their Oxidation number ( Oxidation state The electron is a fundamental Subatomic particle that was identified and assigned the negative charge in 1897 by J This action catalyzes reactions that produce reactive radicals and can produce reactive oxygen species. Catalysis is the process in which the rate of a Chemical reaction is increased by means of a Chemical substance known as a catalyst In Chemistry, radicals (often referred to as free radicals) are atoms molecules or ions with Unpaired electrons on an otherwise Open shell Reactive oxygen species (ROS are ions or very small molecules that include Oxygen Ions free radicals, and Peroxides both inorganic and The most important reactions are probably Fenton's reaction and the Haber-Weiss reaction, in which hydroxyl radical is produced from reduced iron and hydrogen peroxide. Henry John Horstman Fenton (1854-1929 was a British Chemical engineer who in the 1890s invented Fenton's reagent, a Solution of Hydrogen peroxide Hydroxyl in Chemistry describes a molecule consisting of an Oxygen atom and a Hydrogen atom joined by a Covalent bond. 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, and oxidize nucleobases. Tyrosine (abbreviated as Tyr or Y) or 4-hydroxyphenylalanine, is one of the 20 Amino acids that are used by cells to synthesize Tyrosine (abbreviated as Tyr or Y) or 4-hydroxyphenylalanine, is one of the 20 Amino acids that are used by cells to synthesize Phe redirects here For the BitTorrent feature see PHE. For the constellation see Phoenix (constellation. Most enzymes that produce reactive oxygen species contain one of these metals. The presence of such metals in biological systems in an uncomplexed form (not in a protein or other protective metal complex) can significantly increase the level of oxidative stress. In humans, hemochromatosis is associated with increased tissue iron levels, Wilson's disease with increased tissue levels of copper. Haemochromatosis, also spelled hemochromatosis (see spelling differences) also called siderophilia Wilson's disease or hepatolenticular degeneration is an Autosomal recessive Genetic disorder in which Copper accumulates in tissues and chronic manganism with exposure to manganese ores. Manganism or manganese Poisoning is a Toxic condition resulting from chronic exposure to Manganese and first identified in 1837 by James

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 quinones. "DDQ" redirects here DDQ is also the former callsign of a TV station in Toowoomba Queensland Australia Quinones can redox cycle with their conjugate semiquinones and hydroquinones, in some cases catalyzing the production of superoxide from dioxygen or hydrogen peroxide from superoxide. An Ubisemiquinone is a Free radical resulting from the removal of one hydrogen atom with its electron during the process of Dehydrogenation of a Hydroquinone Hydroquinone, also benzene-14-diol or quinol, is an Aromatic Organic compound which is a type of phenol, having the Chemical Oxidative stress generated by the reducing agent uric acid may be involved in the Lesch-Nyhan syndrome, stroke, and metabolic syndrome. Uric acid (or urate) is an Organic compound of Carbon, Nitrogen, Oxygen and Hydrogen with the formula C5H4N4O3 Lesch-Nyhan syndrome ( LNS) also known as Nyhan’s syndrome or Kelley-Seegmiller syndrome, is a rare Inherited disorder caused by a deficiency A stroke is the rapidly developing loss of brain functions due to a disturbance in the blood vessels supplying blood to the brain Metabolic syndrome is a combination of medical disorders that increase the risk of developing Cardiovascular disease and diabetes. Likewise, production of reactive oxygen species in the presence of homocysteine may figure in homocystinuria, as well as atherosclerosis, stroke, and Alzheimers. Homocysteine is a Chemical compound with the formula HSCH2CH2CH(NH2CO2H Homocystinuria, also known as Cystathionine beta synthase deficiency, is an inherited disorder of the Metabolism of the Amino acid Methionine Atherosclerosis is a Disease affecting arterial Blood vessels It is a chronic inflammatory response in the walls of arteries in large part due to the accumulation A stroke is the rapidly developing loss of brain functions due to a disturbance in the blood vessels supplying blood to the brain Alzheimer's disease ( AD) also called Alzheimer disease or simply Alzheimer's, is the most common form of Dementia.

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. Phagocytes are cells that are found in the blood bone marrow and other tissues of Vertebrates. These include superoxide (•O2-), nitric oxide (•NO) and their particularly reactive product, peroxynitrite (ONOO-). [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.

External links

See also

References

  1. ^ Schafer FQ, Buettner GR (2001). Acatalasia (also called acatalasemia, or Takahara's disease) is an Autosomal recessive Peroxisomal disorder caused by a complete lack of Nitric oxide or nitrogen monoxide is a Chemical compound with Chemical formula N[[Oxygen O]] Denham Harman (born February 14, 1916) MD PhD FACP FAAA biogerontologist is Professor Emeritus at the University of Nebraska Medical Harry B Demopoulos MD, is an important pioneer in the medical aspects of Free radicals, especially in the areas of Ischaemic injury the toxicity of anticancer Michael Ristow (b April 24, 1967) is a German Medical researcher who has published influential articles on the metabolic basis of human Pro-oxidants are chemicals that induce Oxidative stress, either through creating Reactive oxygen species or inhibiting Antioxidant systems Redox signaling is the process wherein Free radicals, Reactive oxygen species (ROS and other electronically-activated species act as messengers in biological systems Hormesis (from Hellenistic Greek hórmēsis "rapid motion eagerness" from ancient Greek hormáein "to set in motion impel urge on" is "Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple". Free Radic. Biol. Med. 30 (11): 1191–212. PMID 11368918.  
  2. ^ Lennon SV, Martin SJ, Cotter TG (1991). "Dose-dependent induction of apoptosis in human tumour cell lines by widely diverging stimuli". Cell Prolif. 24 (2): 203–14. PMID 2009322.  
  3. ^ Valko M, Morris H, Cronin MT (May 2005). "Metals, toxicity and oxidative stress". Curr. Med. Chem. 12 (10): 1161–208. doi:10.2174/0929867053764635. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15892631.  
  4. ^ Lelli JL, Becks LL, Dabrowska MI, Hinshaw DB (1998). "ATP converts necrosis to apoptosis in oxidant-injured endothelial cells". Free Radic. Biol. Med. 25 (6): 694–702. PMID 9801070.  
  5. ^ Lee YJ, Shacter E (1999). "Oxidative stress inhibits apoptosis in human lymphoma cells". J. Biol. Chem. 274 (28): 19792–8. PMID 10391922.  
  6. ^ Sies, H. (1985). "Oxidative stress: introductory remarks", in H. Sies, (Ed. ): Oxidative Stress. Academic Press, 1-7.  
  7. ^ Docampo, R. (1995). "Antioxidant mechanisms", in J. Marr and M. Müller, (Eds. ): Biochemistry and Molecular Biology of Parasites. London: Academic Press, 147-160.  
  8. ^ a b Rice-Evans CA, Gopinathan V (1995). "Oxygen toxicity, free radicals and antioxidants in human disease: biochemical implications in atherosclerosis and the problems of premature neonates". Essays Biochem. 29: 39–63. PMID 9189713.  
  9. ^ Meyers DG, Maloley PA, Weeks D (1996). "Safety of antioxidant vitamins". Arch. Intern. Med. 156 (9): 925–35. PMID 8624173.  
  10. ^ Ruano-Ravina A, Figueiras A, Freire-Garabal M, Barros-Dios JM (2006). "Antioxidant vitamins and risk of lung cancer". Curr. Pharm. Des. 12 (5): 599–613. PMID 16472151.  
  11. ^ Pryor WA (2000). "Vitamin E and heart disease: basic science to clinical intervention trials". Free Radic. Biol. Med. 28 (1): 141–64. PMID 10656300.  
  12. ^ Boothby LA, Doering PL (2005). "Vitamin C and vitamin E for Alzheimer's disease". Ann Pharmacother 39 (12): 2073–80. doi:10.1345/aph.1E495. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16227450.  
  13. ^ Kontush K, Schekatolina S (2004). "Vitamin E in neurodegenerative disorders: Alzheimer's disease". Ann. N. Y. Acad. Sci. 1031: 249–62. doi:10.1196/annals.1331.025. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15753151.  
  14. ^ Fong JJ, Rhoney DH (2006). "NXY-059: review of neuroprotective potential for acute stroke". Ann Pharmacother 40 (3): 461–71. doi:10.1345/aph.1E636. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16507608.  
  15. ^ Larsen PL (1993). "Aging and resistance to oxidative damage in Caenorhabditis elegans". Proc. Natl. Acad. Sci. U. S. A. 90 (19): 8905–9. PMID 8415630.  
  16. ^ Helfand SL, Rogina B (2003). "Genetics of aging in the fruit fly, Drosophila melanogaster". Annu. Rev. Genet. 37: 329–48. doi:10.1146/annurev.genet.37.040103.095211. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 14616064.  
  17. ^ Publication demonstrating that oxidative stress is promoting life span
  18. ^ Tapia PC (2006). "Sublethal mitochondrial stress with an attendant stoichiometric augmentation of reactive oxygen species may precipitate many of the beneficial alterations in cellular physiology produced by caloric restriction, intermittent fasting, exercise and dietary phytonutrients: "Mitohormesis" for health and vitality". Med. Hypotheses 66 (4): 832–43. doi:10.1016/j.mehy.2005.09.009. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16242247.  
  19. ^ Sohal RS, Mockett RJ, Orr WC (2002). "Mechanisms of aging: an appraisal of the oxidative stress hypothesis". Free Radic. Biol. Med. 33 (5): 575–86. PMID 12208343.  
  20. ^ Sohal RS (2002). "Role of oxidative stress and protein oxidation in the aging process". Free Radic. Biol. Med. 33 (1): 37–44. PMID 12086680.  
  21. ^ Rattan SI (2006). "Theories of biological aging: genes, proteins, and free radicals". Free Radic. Res. 40 (12): 1230–8. doi:10.1080/10715760600911303. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17090411.  
  22. ^ Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C (2007). "Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis". JAMA 297 (8): 842–57. doi:10.1001/jama.297.8.842. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17327526.  
  23. ^ Nathan C, Shiloh MU (2000). "Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens" (PDF). Proc. Natl. Acad. Sci. U. S. A. 97 (16): 8841–8. PMID 10922044.  
© 2009 citizendia.org; parts available under the terms of GNU Free Documentation License, from http://en.wikipedia.org
 Dapyx Software network: MP3 Explorer | Ebook Manager | Zenithic