My watch list
my.chemeurope.com  

my.chemeurope.com

With an accout for my.chemeurope.com you can always see everything at a glance – and you can configure your own website and individual newsletter.

  • My watch list
  • My saved searches
  • My saved topics
  • My newsletter
Register free of charge
Login  
eng  
DeutschEnglishFrançaisEspañol

Antioxidant



 

An antioxidant is a molecule capable of slowing or preventing the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons from a substance to an oxidizing agent. Oxidation reactions can produce free radicals, which start chain reactions that damage cells. Antioxidants terminate these chain reactions by removing free radical intermediates, and inhibit other oxidation reactions by being oxidized themselves. As a result, antioxidants are often reducing agents such as thiols or polyphenols.

Although oxidation reactions are crucial for life, they can also be damaging; hence, plants and animals maintain complex systems of multiple types of antioxidants, such as glutathione, vitamin C, and vitamin E as well as enzymes such as catalase, superoxide dismutase and various peroxidases. Low levels of antioxidants, or inhibition of the antioxidant enzymes, causes oxidative stress and may damage or kill cells.

As oxidative stress might be an important part of many human diseases, the use of antioxidants in pharmacology is intensively studied, particularly as treatments for stroke and neurodegenerative diseases. However, it is unknown whether oxidative stress is the cause or the consequence of disease. Antioxidants are also widely used as ingredients in dietary supplements in the hope of maintaining health and preventing diseases such as cancer and coronary heart disease. Although some studies have suggested antioxidant supplements have health benefits, other large clinical trials did not detect any benefit for the formulations tested, and excess supplementation may occasionally be harmful. In addition to these uses in medicine, antioxidants have many industrial uses, such as preservatives in food and cosmetics and preventing the degradation of rubber and gasoline.

Contents

History

The term antioxidant originally was used to refer specifically to a chemical that prevented the consumption of oxygen. In the late 19th and early 20th century, extensive study was devoted to the uses of antioxidants in important industrial processes, such as the prevention of metal corrosion, the vulcanization of rubber, and the polymerization of fuels in the fouling of internal combustion engines.[1]

Early research on the role of antioxidants in biology focused on their use in preventing the oxidation of unsaturated fats, which is the cause of rancidity.[2] Antioxidant activity could be measured simply by placing the fat in a closed container with oxygen and measuring the rate of oxygen consumption. However, it was the identification of vitamins A, C, and E as antioxidants that revolutionized the field and led to the realization of the importance of antioxidants in biochemistry of living organisms.[3][4]

The possible mechanisms of action of antioxidants were first explored when it was recognized that a substance with anti-oxidative activity is likely to be one that is itself readily oxidized.[5] Research into how vitamin E prevents the process of lipid peroxidation led to the identification of antioxidants as reducing agents that prevent oxidative reactions, often by scavenging reactive oxygen species before they can damage cells.[6]

The oxidative challenge in biology

Further information: Oxidative stress

 

A paradox in metabolism is that while the vast majority of complex life requires oxygen for its existence, oxygen is a highly reactive molecule that damages living organisms by producing reactive oxygen species.[7] Consequently, organisms contain a complex network of antioxidant metabolites and enzymes that work together to prevent oxidative damage to cellular components such as DNA, proteins and lipids.[8][9] In general, antioxidant systems either prevent these reactive species from being formed, or remove them before they can damage vital components of the cell.[8][7]

The reactive oxygen species produced in cells include hydrogen peroxide (H2O2), hypochlorous acid (HClO), and free radicals such as the hydroxyl radical (·OH) and the superoxide anion (O2−).[10] The hydroxyl radical is particularly unstable and will react rapidly and non-specifically with most biological molecules. This species is produced from hydrogen peroxide in metal-catalyzed redox reactions such as the Fenton reaction.[11] These oxidants can damage cells by starting chemical chain reactions such as lipid peroxidation, or by oxidizing DNA or proteins.[8] Damage to DNA can cause mutations and possibly cancer, if not reversed by DNA repair mechanisms,[12][13] while damage to proteins causes enzyme inhibition, denaturation and protein degradation.[14]

The use of oxygen as part of the process for generating metabolic energy produces reactive oxygen species.[15] In this process, the superoxide anion is produced as a by-product of several steps in the electron transport chain.[16] Particularly important is the reduction of coenzyme Q in complex III, since a highly reactive free radical is formed as an intermediate (Q·−). This unstable intermediate can lead to electron "leakage" when electrons jump directly to molecular oxygen and form the superoxide anion, instead of moving through the series of well-controlled reactions of the electron transport chain.[17] In a similar set of reactions in plants, reactive oxygen species are also produced during photosynthesis under conditions of high light intensity.[18] This effect is partly offset by the involvement of carotenoids in photoinhibition, which involves these antioxidants reacting with over-reduced forms of the photosynthetic reaction centres and thereby preventing superoxide production.[19]

Metabolites

Overview

Antioxidants are classified into two broad divisions, depending on whether they are soluble in water (hydrophilic) or in lipids (hydrophobic). In general, water-soluble antioxidants react with oxidants in the cell cytoplasm and the blood plasma, while lipid-soluble antioxidants protect cell membranes from lipid peroxidation.[8] These compounds may be synthesized in the body or obtained from the diet.[9] The different antioxidants are present at a wide range of concentrations in body fluids and tissues, with some such as glutathione or ubiquinone mostly present within cells, while others such as uric acid are more evenly distributed throughout the body (see table below).

The relative importance and interactions between these different antioxidants is a complex area, with the various metabolites and enzyme systems having synergistic and interdependent effects on one another.[20][21] The action of one antioxidant may depend on the proper function of other members of the antioxidant system.[9] The amount of protection provided by any one antioxidant therefore depends on its concentration, its reactivity towards the particular reactive oxygen species being considered, and the status of the antioxidants with which it interacts.[9]

Some compounds contribute to antioxidant defense by chelating transition metals and preventing them from catalyzing the production of free radicals in the cell. Particularly important is the ability to sequester iron, which is the function of iron-binding proteins such as transferrin and ferritin.[22] Selenium and zinc are commonly referred to as antioxidant nutrients, but these chemical elements have no antioxidant action themselves and are instead required for the activity of some antioxidant enzymes, as is discussed below.

Antioxidant metabolite Solubility Concentration in human serum (μM)[23] Concentration in liver tissue (μmol/kg)
Ascorbic acid (vitamin C) Water 50 – 60[24] 260 (human)[25]
Glutathione Water 325 – 650[26] 6,400 (human)[25]
Lipoic acid Water 0.1 – 0.7[27] 4 – 5 (rat)[28]
Uric acid Water 200 – 400[29] 1,600 (human)[25]
Carotenes Lipid β-carotene: 0.5 – 1[30]

retinol (vitamin A): 1 – 3[31]

5 (human, total carotenoids)[32]
α-tocopherol (vitamin E) Lipid 10 – 40[31] 50 (human)[25]
Ubiquinol (coenzyme Q) Lipid 5[33] 200 (human)[34]

Ascorbic acid

Ascorbic acid or "vitamin C" is a monosaccharide antioxidant found in both animals and plants. As it cannot be synthesised in humans and must be obtained from the diet, it is a vitamin.[35] Most other animals are able to produce this compound in their bodies and do not require it in their diets.[36] In cells, it is maintained in its reduced form by reaction with glutathione, which can be catalysed by protein disulfide isomerase and glutaredoxins.[37][38] Ascorbic acid is a reducing agent and can reduce and thereby neutralize reactive oxygen species such as hydrogen peroxide.[39] In addition to its direct antioxidant effects, ascorbic acid is also a substrate for the antioxidant enzyme ascorbate peroxidase, a function that is particularly important in stress resistance in plants.[40]

Glutathione

 

Glutathione is a cysteine-containing peptide found in most forms of aerobic life.[41] It is not required in the diet and is instead synthesized in cells from its constituent amino acids.[42] Glutathione has antioxidant properties since the thiol group in its cysteine moiety is a reducing agent and can be reversibly oxidized and reduced. In cells, glutathione is maintained in the reduced form by the enzyme glutathione reductase and in turn reduces other metabolites and enzyme systems as well as reacting directly with oxidants.[37] Due to its high concentration and its central role in maintaining the cell's redox state, glutathione is one of the most important cellular antioxidants.[41]

Melatonin

Melatonin is a powerful antioxidant that can easily cross cell membranes and the blood-brain barrier.[43] Unlike other antioxidants, melatonin does not undergo redox cycling, which is the ability of a molecule to undergo repeated reduction and oxidation. Redox cycling may allow other antioxidants (such as vitamin C) to act as pro-oxidants and promote free radical formation. Melatonin, once oxidized, cannot be reduced to its former state because it forms several stable end-products upon reacting with free radicals. Therefore, it has been referred to as a terminal (or suicidal) antioxidant.[44]

Tocopherols and tocotrienols (vitamin E)

Vitamin E is the collective name for a set of eight related tocopherols and tocotrienols, which are fat-soluble antioxidant vitamins.[45] Of these, α-tocopherol has been most studied as it has the highest bioavailability, with the body preferentially absorbing and metabolising this form.[46] It has been suggested that the α-tocopherol form is the most important lipid-soluble antioxidant, and that it protects membranes from oxidation by reacting with lipid radicals produced in the lipid peroxidation chain reaction.[45][47] This removes the free radical intermediates and prevents the propagation reaction from continuing. The oxidised α-tocopheroxyl radicals produced in this process may be recycled back to the active reduced form through reduction by ascorbate, retinol or ubiquinol.[48] The functions of the other forms of vitamin E are less well-studied, although γ-tocopherol is a nucleophile that may react with electrophilic mutagens,[46] and tocotrienols may have a specialised role in neuroprotection.[49] However, the roles and importance of the various forms of vitamin E are presently unclear,[50] and it has even been suggested that the most important function of α-tocopherol is as a signaling molecule, with this molecule having no significant role in antioxidant metabolism.[51]

Pro-oxidant activities

Further information: Pro-oxidant

Antioxidants that are reducing agents can also act as pro-oxidants. For example, vitamin C has antioxidant activity when it reduces oxidizing substances such as hydrogen peroxide,[52] however, it can also reduce metal ions which leads to the generation of free radicals through the Fenton reaction.[53][54]

2 Fe3+ + Ascorbate → 2 Fe2+ + Dehydroascorbate
2 Fe2+ + 2 H2O2 → 2 Fe3+ + 2 OH· + 2 OH−

The relative importance of the antioxidant and pro-oxidant activities of antioxidants are an area of current research, but vitamin C, for example, appears to have a mostly antioxidant action in the body.[55][53] However, less data is available for other dietary antioxidants, such as polyphenol antioxidants,[56] zinc,[57] and vitamin E.[58]

Enzyme systems

 

Overview

As with the chemical antioxidants, cells are protected against oxidative stress by an interacting network of antioxidant enzymes.[8][7] Here, the superoxide released by processes such as oxidative phosphorylation is first converted to hydrogen peroxide and then further reduced to give water. This detoxification pathway is the result of multiple enzymes, with superoxide dismutases catalysing the first step and then catalases and various peroxidases removing hydrogen peroxide. As with antioxidant metabolites, the contributions of these enzymes can be hard to separate from one another, but the generation of transgenic mice lacking just one antioxidant enzyme can be informative.[59]

Superoxide dismutase, catalase and peroxiredoxins

Superoxide dismutases (SODs) are a class of closely related enzymes that catalyse the breakdown of the superoxide anion into oxygen and hydrogen peroxide.[60][61] SOD enzymes are present in almost all aerobic cells and in extracellular fluids.[62] Superoxide dismutase enzymes contain metal ion cofactors that, depending on the isozyme, can be copper, zinc, manganese or iron. In humans, the copper/zinc SOD is present in the cytosol, while manganese SOD is present in the mitochondrion.[61] There also exists a third form of SOD in extracellular fluids, which contains copper and zinc in its active sites.[63] The mitochondrial isozyme seems to be the most biologically important of these three, since mice lacking this enzyme die soon after birth.[64] In contrast, the mice lacking copper/zinc SOD are viable but have lowered fertility, while mice without the extracellular SOD have minimal defects.[59][65] In plants, SOD isozymes are present in the cytosol and mitochondria, with an iron SOD found in chloroplasts that is absent from vertebrates and yeast.[66]

Catalases are enzymes that catalyse the conversion of hydrogen peroxide to water and oxygen, using either an iron or manganese cofactor.[67][68] This protein is localized to peroxisomes in most eukaryotic cells.[69] Catalase is an unusual enzyme since, although hydrogen peroxide is its only substrate, it follows a ping-pong mechanism. Here, its cofactor is oxidised by one molecule of hydrogen peroxide and then regenerated by transferring the bound oxygen to a second molecule of substrate.[70] Despite its apparent importance in hydrogen peroxide removal, humans with genetic deficiency of catalase — "acatalasemia" — or mice genetically engineered to lack catalase completely, suffer few ill effects.[71][72]

 

Peroxiredoxins are peroxidases that catalyze the reduction of hydrogen peroxide, organic hydroperoxides, as well as peroxynitrite.[74] They are divided into three classes: typical 2-cysteine peroxiredoxins; atypical 2-cysteine peroxiredoxins; and 1-cysteine peroxiredoxins.[75] These enzymes share the same basic catalytic mechanism, in which a redox-active cysteine (the peroxidatic cysteine) in the active site is oxidized to a sulfenic acid by the peroxide substrate.[76] Peroxiredoxins seem to be important in antioxidant metabolism, as mice lacking peroxiredoxin 1 or 2 have shortened lifespan and suffer from hemolytic anaemia, while plants use peroxiredoxins to remove hydrogen peroxide generated in chloroplasts.[77][78][79]

Thioredoxin and glutathione systems

The thioredoxin system contains the 12-kDa protein thioredoxin and its companion thioredoxin reductase.[80] Proteins related to thioredoxin are present in all sequenced organisms, with plants such as Arabidopsis thaliana having a particularly great diversity of isoforms.[81] The active site of thioredoxin consists of two neighboring cysteines, as part of a highly-conserved CXXC motif, that can cycle between an active dithiol form (reduced) and an oxidized disulfide form. In its active state, thioredoxin acts as an efficient reducing agent, scavenging reactive oxygen species and maintaining other proteins in their reduced state.[82] After being oxidized, the active thioredoxin is regenerated by the action of thioredoxin reductase, using NADPH as an electron donor.[83]

The glutathione system includes glutathione, glutathione reductase, glutathione peroxidases and glutathione S-transferases.[41] This system is found in animals, plants and microorganisms.[84][41] Glutathione peroxidase is an enzyme containing four selenium-cofactors that catalyzes the breakdown of hydrogen peroxide and organic hydroperoxides. There are at least four different glutathione peroxidase isozymes in animals.[85] Glutathione peroxidase 1 is the most abundant and is a very efficient scavenger of hydrogen peroxide, while glutathione peroxidase 4 is most active with lipid hydroperoxides. Surprisingly, glutathione peroxidase 1 is dispensable, as mice lacking this enzyme have normal lifespans,[86] but they are hypersensitive to induced oxidative stress.[87] In addition, the glutathione S-transferases are another class of glutathione-dependent antioxidant enzymes that show high activity with lipid peroxides.[88] These enzymes are at particularly high levels in the liver and also serve in detoxification metabolism.[89]

Oxidative stress in disease

Further information: Pathology, Free-radical theory of ageing

Oxidative stress is thought to contribute to the development of a wide range of diseases including Alzheimer's disease,[90][91] Parkinson's disease,[92] the pathologies caused by diabetes,[93][94] rheumatoid arthritis,[95] and neurodegeneration in motor neurone diseases.[96] In many of these cases, it is unclear if oxidants trigger the disease, or if they are produced as a consequence of the disease and cause the disease symptoms;[97] as a plausible alternative, a neurodegenerative disease might result from defective axonal transport of mitochondria, which carry out oxidation reactions. One case in which this link is particularly well-understood is the role of oxidative stress in cardiovascular disease. Here, low density lipoprotein (LDL) oxidation appears to trigger the process of atherogenesis, which results in atherosclerosis, and finally cardiovascular disease.[98][99]

A low calorie diet extends median and maximum lifespan in many animals. This effect may involve a reduction in oxidative stress.[100] While there is good evidence to support the role of oxidative stress in aging in model organisms such as Drosophila melanogaster and Caenorhabditis elegans,[101][102] the evidence in mammals is less clear.[103][104][105] Diets high in fruit and vegetables, which are high in antioxidants, promote health and reduce the effects of ageing, however antioxidant vitamin supplementation has no detectable effect on the ageing process, so the effects of fruit and vegetables may be unrelated to their antioxidant contents.[106][107]

Health effects

Disease treatment

The brain is uniquely vulnerable to oxidative injury, due to its high metabolic rate and elevated levels of polyunsaturated lipids, the target of lipid peroxidation.[108] Consequently, antioxidants are commonly used as medications to treat various forms of brain injury. Here, superoxide dismutase mimetics,[109] sodium thiopental and propofol are used to treat reperfusion injury and traumatic brain injury,[110] while the experimental drug NXY-059[111][112] and ebselen[113] are being applied in the treatment of stroke. These compounds appear to prevent oxidative stress in neurons and prevent apoptosis and neurological damage. Antioxidants are also being investigated as possible treatments for neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.[114][115]

Disease prevention

 

Antioxidants can cancel out the cell-damaging effects of free radicals,[8] and people who eat fruits and vegetables rich in polyphenols and anthocyanins have a lower risk of cancer, heart disease and some neurological diseases.[116] This observation suggested that these compounds might prevent conditions such as macular degeneration,[117] suppressed immunity due to poor nutrition,[118] and neurodegeneration, which are caused by oxidative stress.[119] However, despite the clear role of oxidative stress in cardiovascular disease, controlled studies using antioxidant vitamins have observed no reduction in either the risk of developing heart disease, or the rate of progression of existing disease.[120][121] This suggests that other substances in fruit and vegetables (possibly flavonoids) at least partially explain the better cardiovascular health of those who consume more fruit and vegetables.[122]

It is thought that oxidation of low density lipoprotein in the blood contributes to heart disease, and initial observational studies found that people taking Vitamin E supplements had a lower risk of developing heart disease.[123] Consequently, at least seven large clinical trials were conducted to test the effects of antioxidant supplement with Vitamin E, in doses ranging from 50 to 600 mg per day. However, none of these trials found a statistically significant effect of Vitamin E on overall number of deaths or on deaths due to heart disease.[124] It is not clear if the doses used in these trials or in most dietary supplements are capable of producing any significant decrease in oxidative stress.[125]

While several trials have investigated supplements with high doses of antioxidants, the "Supplémentation en Vitamines et Mineraux Antioxydants" (SU.VI.MAX) study tested the effect of supplementation with doses comparable to those in a healthy diet.[126] Over 12,500 French men and women took either low-dose antioxidants (120 mg of ascorbic acid, 30 mg of vitamin E, 6 mg of beta carotene, 100 μg of selenium, and 20 mg of zinc) or placebo pills for an average of 7.5 years. The investigators found there was no statistically significant effect of the antioxidants on overall survival, cancer, or heart disease. However, a subgroup analysis showed a 31% reduction in the risk of cancer in men, but not women.

Many nutraceutical and health food companies now sell formulations of antioxidants as dietary supplements and these are widely used in industrialized countries.[127] These supplements may include specific antioxidant chemicals, like resveratrol (from grape seeds), combinations of antioxidants, like the "ACES" products that contain beta carotene (provitamin A), vitamin C, vitamin E and Selenium, or herbs that contain antioxidants - such as green tea and jiaogulan. Although some levels of antioxidant vitamins and minerals in the diet are required for good health, there is considerable doubt as to whether antioxidant supplementation is beneficial, and if so, which antioxidant(s) are beneficial and in what amounts.[128][129][116]

It has been suggested that moderate levels of oxidative stress may increase life expectancy of in the worm Caenorhabditis elegans, by inducing a protective response to increased levels of reactive oxygen species.[130] However, the suggestion that increased life expectancy comes from increased oxidative stress conflicts with results seen in the yeast Saccharomyces cerevisiae,[131] and the situation in mammals is even less clear.[132][133][134]

Physical exercise

During exercise, oxygen consumption can increase by a factor of more than 10.[135] This leads to a large increase in the production of oxidants and results in damage that contributes to muscular fatigue during and after exercise. The inflammatory response that occurs after strenuous exercise is also associated with oxidative stress, especially in the 24 hours after an exercise session. The immune system response to damage done by exercise peaks 2 to 7 days after exercise, the period during which adaptation resulting in greater fitness is greatest. During this process, free radicals are produced by neutrophils to remove damaged tissue. As a result, excessive antioxidant levels have the potential to inhibit recovery and adaptation mechanisms.[136]

The evidence for benefits from antioxidant supplementation in vigorous exercise is mixed. There is strong evidence that one of the adaptations resulting from exercise is a strengthening of the body's antioxidant defenses, particularly the glutathione system, to deal with the increased oxidative stress.[137] It is possible that this effect may be to some extent protective against diseases which are associated with oxidative stress, which would provide a partial explanation for the lower incidence of major diseases and better health of those who undertake regular exercise.[138]

However, no benefits to athletes are seen with vitamin A or E supplementation.[139] For example, despite its key role in preventing lipid membrane peroxidation, 6 weeks of vitamin E supplementation had no effect on muscle damage in ultramarathon runners.[140] Although there appears to be no increased requirement for vitamin C in athletes, there is some evidence that vitamin C supplementation increased the amount of intense exercise that can be done and vitamin C supplementation before strenuous exercise may reduce the amount of muscle damage.[141][142] However, other studies found no such effects, and some research suggests that supplementation with amounts as high as 1000 mg inhibits recovery.[143]

Adverse effects

Further information: Micronutrients

 

Relatively strong reducing acids can have anti-nutritional effects by binding to dietary minerals such as iron and zinc in the gastrointestinal tract and preventing them from being absorbed.[144] Notable examples are oxalic acid, tannins and phytic acid, which are high in plant-based diets.[145] Calcium and iron deficiencies are not uncommon in diets in developing countries where less meat is eaten and there is high consumption of phytic acid from beans and unleavened whole grain bread.[146]

Foods Reducing acid present
Cocoa and chocolate, spinach, turnip and rhubarb.[147] Oxalic acid
Whole grains, maize, legumes.[148] Phytic acid
Tea, beans, cabbage.[149][147] Tannins

Nonpolar antioxidants such as eugenol, a major component of oil of cloves have toxicity limits that can be exceeded with the misuse of undiluted essential oils.[150] Toxicity associated with high doses of water-soluble antioxidants such as ascorbic acid are less of a concern, as these compounds can be excreted rapidly in urine.[151] More seriously, very high doses of some antioxidants may have harmful long-term effects. The beta-Carotene and Retinol Efficacy Trial (CARET) study of lung cancer patients found that smokers given supplements containing beta-carotene and vitamin A had increased rates of lung cancer.[152] Subsequent studies confirmed these adverse effects.[153]

These harmful effects may also be seen in non-smokers, as a recent meta-analysis including data from approximately 230,000 patients showed that β-carotene, vitamin A or vitamin E supplementation is associated with increased mortality but saw no significant effect from vitamin C.[154] No health risk was seen when all the randomized controlled studies were examined together, but an increase in mortality was detected only when the high-quality and low-bias risk trials were examined separately. However, as the majority of these low-bias trials dealt with either elderly people, or people already suffering disease, these results may not apply to the general population.[155] These results are consistent with some previous meta-analyses that also suggested that Vitamin E supplementation increased mortality,[156] and that antioxidant supplements increased the risk of colon cancer.[157] However, the results of this meta-analysis are inconsistent with other studies such as the SU.VI.MAX trial, which suggested that antioxidants have no effect on cause-all mortality.[126][158][159][160] Overall, the large number of clinical trials carried out on antioxidant supplements suggest that either these products have no effect on health, or that they cause a small increase in mortality in elderly or vulnerable populations.[128][116][154]

While antioxidant supplementation is widely used in attempts to prevent the development of cancer, it has been proposed that antioxidants may, paradoxically, interfere with cancer treatments.[161] This was thought to occur since the environment of cancer cells causes high levels of oxidative stress, making these cells more susceptible to the further oxidative stress induced by treatments. As a result, by reducing the redox stress in cancer cells, antioxidant supplements were thought to decrease the effectiveness of radiotherapy and chemotherapy.[162] However, this concern appears not to be valid, as it has been addressed by multiple clinical trials that indicate that antioxidants are either neutral or beneficial in cancer therapy.[163][164]

Measurement and levels in food

Further information: List of antioxidants in food, Polyphenol antioxidants

 

Measurement of antioxidants is not a straightforward process, as this is a diverse group of compounds with different reactivities to different reactive oxygen species. In food science, the oxygen radical absorbance capacity (ORAC) has become the current industry standard for assessing antioxidant strength of whole foods, juices and food additives.[165][166] Other measurement tests include the Folin-Ciocalteu reagent, and the trolox equivalent antioxidant capacity assay.[167] In medicine, a range of different assays are used to assess the antioxidant capability of blood plasma and of these, the ORAC assay may be the most reliable.[168]

Antioxidants are found in varying amounts in foods such as vegetables, fruits, grain cereals, legumes and nuts. Some antioxidants such as lycopene and ascorbic acid can be destroyed by long-term storage or prolonged cooking.[169][170] Other antioxidant compounds are more stable, such as the polyphenolic antioxidants in foods such as whole-wheat cereals and tea.[171][172] In general, processed foods contain less antioxidants than fresh and uncooked foods, since the preparation processes may expose the food to oxygen.[173]

Antioxidant compounds Foods containing high levels of these antioxidants[174][149]
Vitamin C (ascorbic acid) Fruits and vegetables
Vitamin E (tocopherols, tocotrienols) Vegetable oils
Polyphenolic antioxidants (resveratrol, flavonoids) Tea, coffee, soy, fruit, chocolate, oregano and red wine.
Carotenoids (lycopene, carotenes) Fruit and vegetables

Some antioxidants are made in the body and are not absorbed from the intestine. One example is glutathione, which is made from amino acids. As any glutathione in the gut is broken down to free cysteine, glycine and glutamic acid before being absorbed, even large oral doses have little effect on the concentration of glutathione in the body.[175] Ubiquinol (coenzyme Q) is also poorly absorbed from the gut and is made in humans through the mevalonate pathway.[34]

Uses in technology

Food preservatives

Antioxidants are used as food additives to help guard against food deterioration. Exposure to oxygen and sunlight are the two main factors in the oxidation of food, so food is preserved by keeping in the dark and sealing it in containers or even coating it in wax, as with cucumbers. However, as oxygen is also important for plant respiration, storing plant materials in anaerobic conditions produces unpleasant flavors and unappealing colors.[176] Consequently, packaging of fresh fruits and vegetables contains an ~8% oxygen atmosphere. Antioxidants are an especially important class of preservatives as, unlike bacterial or fungal spoilage, oxidation reactions still occur relatively rapidly in frozen or refrigerated food.[177] These preservatives include ascorbic acid (AA, E300), propyl gallate (PG, E310), tocopherols (E306), tertiary butylhydroquinone (TBHQ), butylated hydroxyanisole (BHA, E320) and butylated hydroxytoluene (BHT, E321).[178][179]

The most common molecules attacked by oxidation are unsaturated fats; oxidation causes them to turn rancid.[180] Since oxidized lipids are often discolored and usually have unpleasant tastes such as metallic or sulfurous flavors, it is important to avoid oxidation in fat-rich foods. Thus, these foods are rarely preserved by drying; instead, they are preserved by smoking, salting or fermenting. Even less fatty foods such as fruits are sprayed with sulfurous antioxidants prior to air drying. Oxidation is often catalyzed by metals, which is why fats such as butter should never be wrapped in aluminium foil or kept in metal containers. Some fatty foods such as olive oil are partially protected from oxidation by their natural content of antioxidants, but remain sensitive to photooxidation.[181]

Industrial uses

Some antioxidants are added to industrial products. A common use is as stabilizers in fuels and lubricants to prevent oxidation, and in gasolines to prevent the polymerization that leads to the formation of engine-fouling residues.[182] They are also used to prevent the oxidative degradation of rubber, plastics and adhesives that causes a loss of strength and flexibility in these materials.[183] Antioxidant preservatives are also added to fat-based cosmetics such as lipstick and moisturizers to prevent rancidity.

Fuel additive Components[184] Applications[184]
AO-22 N,N'-di-2-butyl-1,4-phenylenediamine Turbine oils, transformer oils, hydraulic fluids, waxes, and greases
AO-24 N,N'-di-2-butyl-1,4-phenylenediamine Low-temperature oils
AO-29 2,6-di-tert-butyl-4-methylphenol Turbine oils, transformer oils, hydraulic fluids, waxes, greases, and gasolines
AO-30 2,4-dimethyl-6-tert-butylphenol Jet fuels and gasolines, including aviation gasolines
AO-31 2,4-dimethyl-6-tert-butylphenol Jet fuels and gasolines, including aviation gasolines
AO-32 2,4-dimethyl-6-tert-butylphenol and 2,6-di-tert-butyl-4-methylphenol Jet fuels and gasolines, including aviation gasolines
AO-37 2,6-di-tert-butylphenol Jet fuels and gasolines, widely approved for aviation fuels

See also


Further reading

  • Nick Lane Oxygen: The Molecule That Made the World (Oxford University Press, 2003) ISBN 0-198-60783-0
  • Barry Halliwell and John M.C. Gutteridge Free Radicals in Biology and Medicine(Oxford University Press, 2007) ISBN 0-198-56869-X
  • Jan Pokorny, Nelly Yanishlieva and Michael H. Gordon Antioxidants in Food: Practical Applications (CRC Press Inc, 2001) ISBN 0-849-31222-1

References

  1. ^ Matill HA (1947). Antioxidants. Annu Rev Biochem 16: 177–192.
  2. ^ German J (1999). "Food processing and lipid oxidation". Adv Exp Med Biol 459: 23–50. PMID 10335367.
  3. ^ Jacob R (1996). "Three eras of vitamin C discovery". Subcell Biochem 25: 1–16. PMID 8821966.
  4. ^ Knight J (1998). "Free radicals: their history and current status in aging and disease". Ann Clin Lab Sci 28 (6): 331-46. PMID 9846200.
  5. ^ Moreau and Dufraisse, (1922) Comptes Rendus des Séances et Mémoires de la Société de Biologie, 86, 321.
  6. ^ Wolf G (2005). "The discovery of the antioxidant function of vitamin E: the contribution of Henry A. Mattill". J Nutr 135 (3): 363-6. PMID 15735064.
  7. ^ a b c Davies K (1995). "Oxidative stress: the paradox of aerobic life". Biochem Soc Symp 61: 1–31. PMID 8660387.
  8. ^ a b c d e f Sies H (1997). "Oxidative stress: oxidants and antioxidants". Exp Physiol 82 (2): 291-5. PMID 9129943.
  9. ^ a b c d Vertuani S, Angusti A, Manfredini S (2004). "The antioxidants and pro-antioxidants network: an overview". Curr Pharm Des 10 (14): 1677–94. PMID 15134565.
  10. ^ Valko M, Leibfritz D, Moncol J, Cronin M, Mazur M, Telser J (2007). "Free radicals and antioxidants in normal physiological functions and human disease". Int J Biochem Cell Biol 39 (1): 44–84. PMID 16978905.
  11. ^ Stohs S, Bagchi D (1995). "Oxidative mechanisms in the toxicity of metal ions". Free Radic Biol Med 18 (2): 321-36. PMID 7744317.
  12. ^ Nakabeppu Y, Sakumi K, Sakamoto K, Tsuchimoto D, Tsuzuki T, Nakatsu Y (2006). "Mutagenesis and carcinogenesis caused by the oxidation of nucleic acids". Biol Chem 387 (4): 373-9. PMID 16606334.
  13. ^ Valko M, Izakovic M, Mazur M, Rhodes C, Telser J (2004). "Role of oxygen radicals in DNA damage and cancer incidence". Mol Cell Biochem 266 (1–2): 37–56. PMID 15646026.
  14. ^ Stadtman E (1992). "Protein oxidation and aging". Science 257 (5074): 1220–4. PMID 1355616.
  15. ^ Raha S, Robinson B (2000). "Mitochondria, oxygen free radicals, disease and ageing". Trends Biochem Sci 25 (10): 502-8. PMID 11050436.
  16. ^ Lenaz G (2001). "The mitochondrial production of reactive oxygen species: mechanisms and implications in human pathology". IUBMB Life 52 (3–5): 159-64. PMID 11798028.
  17. ^ Finkel T, Holbrook NJ (2000). "Oxidants, oxidative stress and the biology of ageing". Nature 408 (6809): 239-47. PMID 11089981.
  18. ^ Krieger-Liszkay A (2005). "Singlet oxygen production in photosynthesis". J Exp Bot 56 (411): 337-46. PMID 15310815.
  19. ^ Szabó I, Bergantino E, Giacometti G (2005). "Light and oxygenic photosynthesis: energy dissipation as a protection mechanism against photo-oxidation". EMBO Rep 6 (7): 629-34. PMID 15995679.
  20. ^ Chaudière J, Ferrari-Iliou R (1999). "Intracellular antioxidants: from chemical to biochemical mechanisms". Food Chem Toxicol 37 (9–10): 949 – 62. PMID 10541450.
  21. ^ Sies H (1993). "Strategies of antioxidant defense". Eur J Biochem 215 (2): 213 – 9. PMID 7688300.
  22. ^ Imlay J (2003). "Pathways of oxidative damage". Annu Rev Microbiol 57: 395–418. PMID 14527285.
  23. ^ Ames B, Cathcart R, Schwiers E, Hochstein P (1981). "Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis". Proc Natl Acad Sci U S A 78 (11): 6858 – 62. PMID 6947260.
  24. ^ Khaw K, Woodhouse P (1995). "Interrelation of vitamin C, infection, haemostatic factors, and cardiovascular disease". BMJ 310 (6994): 1559 – 63. PMID 7787643.
  25. ^ a b c d Evelson P, Travacio M, Repetto M, Escobar J, Llesuy S, Lissi E (2001). "Evaluation of total reactive antioxidant potential (TRAP) of tissue homogenates and their cytosols". Arch Biochem Biophys 388 (2): 261 – 6. PMID 11368163.
  26. ^ Chen C, Qu L, Li B, Xing L, Jia G, Wang T, Gao Y, Zhang P, Li M, Chen W, Chai Z (2005). "Increased oxidative DNA damage, as assessed by urinary 8-hydroxy-2'-deoxyguanosine concentrations, and serum redox status in persons exposed to mercury". Clin Chem 51 (4): 759 – 67. PMID 15695327.
  27. ^ Teichert J, Preiss R (1992). "HPLC-methods for determination of lipoic acid and its reduced form in human plasma". Int J Clin Pharmacol Ther Toxicol 30 (11): 511 – 2. PMID 1490813.
  28. ^ Akiba S, Matsugo S, Packer L, Konishi T (1998). "Assay of protein-bound lipoic acid in tissues by a new enzymatic method". Anal Biochem 258 (2): 299 – 304. PMID 9570844.
  29. ^ Glantzounis G, Tsimoyiannis E, Kappas A, Galaris D (2005). "Uric acid and oxidative stress". Curr Pharm Des 11 (32): 4145 – 51. PMID 16375736.
  30. ^ El-Sohemy A, Baylin A, Kabagambe E, Ascherio A, Spiegelman D, Campos H (2002). "Individual carotenoid concentrations in adipose tissue and plasma as biomarkers of dietary intake". Am J Clin Nutr 76 (1): 172 – 9. PMID 12081831.
  31. ^ a b Sowell A, Huff D, Yeager P, Caudill S, Gunter E (1994). "Retinol, alpha-tocopherol, lutein/zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, trans-beta-carotene, and four retinyl esters in serum determined simultaneously by reversed-phase HPLC with multiwavelength detection". Clin Chem 40 (3): 411 – 6. PMID 8131277.
  32. ^ Stahl W, Schwarz W, Sundquist A, Sies H (1992). "cis-trans isomers of lycopene and beta-carotene in human serum and tissues". Arch Biochem Biophys 294 (1): 173 – 7. PMID 1550343.
  33. ^ Zita C, Overvad K, Mortensen S, Sindberg C, Moesgaard S, Hunter D (2003). "Serum coenzyme Q10 concentrations in healthy men supplemented with 30 mg or 100 mg coenzyme Q10 for two months in a randomised controlled study". Biofactors 18 (1 – 4): 185 – 93. PMID 14695934.
  34. ^ a b Turunen M, Olsson J, Dallner G (2004). "Metabolism and function of coenzyme Q". Biochim Biophys Acta 1660 (1 – 2): 171 – 99. PMID 14757233.
  35. ^ Smirnoff N (2001). "L-ascorbic acid biosynthesis". Vitam Horm 61: 241 – 66. PMID 11153268.
  36. ^ Linster CL, Van Schaftingen E (2007). "Vitamin C. Biosynthesis, recycling and degradation in mammals". FEBS J. 274 (1): 1-22. PMID 17222174.
  37. ^ a b Meister A (1994). "Glutathione-ascorbic acid antioxidant system in animals". J Biol Chem 269 (13): 9397 – 400. PMID 8144521.
  38. ^ Wells W, Xu D, Yang Y, Rocque P (1990). "Mammalian thioltransferase (glutaredoxin) and protein disulfide isomerase have dehydroascorbate reductase activity". J Biol Chem 265 (26): 15361 – 4. PMID 2394726.
  39. ^ Padayatty S, Katz A, Wang Y, Eck P, Kwon O, Lee J, Chen S, Corpe C, Dutta A, Dutta S, Levine M (2003). "Vitamin C as an antioxidant: evaluation of its role in disease prevention". J Am Coll Nutr 22 (1): 18 – 35. PMID 12569111.
  40. ^ Shigeoka S, Ishikawa T, Tamoi M, Miyagawa Y, Takeda T, Yabuta Y, Yoshimura K (2002). "Regulation and function of ascorbate peroxidase isoenzymes". J Exp Bot 53 (372): 1305 – 19. PMID 11997377.
  41. ^ a b c d Meister A, Anderson M (1983). "Glutathione". Annu Rev Biochem 52: 711 – 60. PMID 6137189.
  42. ^ Meister A (1988). "Glutathione metabolism and its selective modification". J Biol Chem 263 (33): 17205 – 8. PMID 3053703.
  43. ^ Reiter RJ, Carneiro RC, Oh CS (1997). "Melatonin in relation to cellular antioxidative defense mechanisms". Horm. Metab. Res. 29 (8): 363-72. PMID 9288572.
  44. ^ Tan DX, Manchester LC, Reiter RJ, Qi WB, Karbownik M, Calvo JR (2000). "Significance of melatonin in antioxidative defense system: reactions and products". Biological signals and receptors 9 (3–4): 137-59. PMID 10899700.
  45. ^ a b Herrera E, Barbas C (2001). "Vitamin E: action, metabolism and perspectives". J Physiol Biochem 57 (2): 43 – 56. PMID 11579997.
  46. ^ a b Brigelius-Flohé R, Traber M (1999). "Vitamin E: function and metabolism". FASEB J 13 (10): 1145 – 55. PMID 10385606.
  47. ^ Traber MG, Atkinson J (2007). "Vitamin E, antioxidant and nothing more". Free Radic. Biol. Med. 43 (1): 4–15. PMID 17561088.
  48. ^ Wang X, Quinn P (1999). "Vitamin E and its function in membranes". Prog Lipid Res 38 (4): 309 – 36. PMID 10793887.
  49. ^ Sen C, Khanna S, Roy S (2006). "Tocotrienols: Vitamin E beyond tocopherols". Life Sci 78 (18): 2088 – 98. PMID 16458936.
  50. ^ Brigelius-Flohé R, Davies KJ (2007). "Is vitamin E an antioxidant, a regulator of signal transduction and gene expression, or a 'junk' food? Comments on the two accompanying papers: "Molecular mechanism of alpha-tocopherol action" by A. Azzi and "Vitamin E, antioxidant and nothing more" by M. Traber and J. Atkinson". Free Radic. Biol. Med. 43 (1): 2–3. PMID 17561087.
  51. ^ Azzi A (2007). "Molecular mechanism of alpha-tocopherol action". Free Radic. Biol. Med. 43 (1): 16–21. PMID 17561089.
  52. ^ Duarte TL, Lunec J (2005). "Review: When is an antioxidant not an antioxidant? A review of novel actions and reactions of vitamin C". Free Radic. Res. 39 (7): 671-86. PMID 16036346.
  53. ^ a b Carr A, Frei B (1999). "Does vitamin C act as a pro-oxidant under physiological conditions?". FASEB J. 13 (9): 1007-24. PMID 10336883.
  54. ^ Stohs SJ, Bagchi D (1995). "Oxidative mechanisms in the toxicity of metal ions". Free Radic. Biol. Med. 18 (2): 321-36. PMID 7744317.
  55. ^ Valko M, Morris H, Cronin MT (2005). "Metals, toxicity and oxidative stress". Curr. Med. Chem. 12 (10): 1161-208. PMID 15892631.
  56. ^ Halliwell B (2007). "Dietary polyphenols: good, bad, or indifferent for your health?". Cardiovasc. Res. 73 (2): 341-7. PMID 17141749.
  57. ^ Hao Q, Maret W (2005). "Imbalance between pro-oxidant and pro-antioxidant functions of zinc in disease". J. Alzheimers Dis. 8 (2): 161-70; discussion 209-15. PMID 16308485.
  58. ^ Schneider C (2005). "Chemistry and biology of vitamin E". Mol Nutr Food Res 49 (1): 7-30. PMID 15580660.
  59. ^ a b Ho Y, Magnenat J, Gargano M, Cao J (9788901). "The nature of antioxidant defense mechanisms: a lesson from transgenic studies". Environ Health Perspect 106 Suppl 5: 1219–28. PMID 9788901.
  60. ^ Zelko I, Mariani T, Folz R (2002). "Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression". Free Radic Biol Med 33 (3): 337-49. PMID 12126755.
  61. ^ a b Bannister J, Bannister W, Rotilio G (1987). "Aspects of the structure, function, and applications of superoxide dismutase". CRC Crit Rev Biochem 22 (2): 111-80. PMID 3315461.
  62. ^ Johnson F, Giulivi C (2005). "Superoxide dismutases and their impact upon human health". Mol Aspects Med 26 (4–5): 340-52. PMID 16099495.
  63. ^ Nozik-Grayck E, Suliman H, Piantadosi C (2005). "Extracellular superoxide dismutase". Int J Biochem Cell Biol 37 (12): 2466–71. PMID 16087389.
  64. ^ Melov S, Schneider J, Day B, Hinerfeld D, Coskun P, Mirra S, Crapo J, Wallace D (1998). "A novel neurological phenotype in mice lacking mitochondrial manganese superoxide dismutase". Nat Genet 18 (2): 159-63. PMID 9462746.
  65. ^ Reaume A, Elliott J, Hoffman E, Kowall N, Ferrante R, Siwek D, Wilcox H, Flood D, Beal M, Brown R, Scott R, Snider W (1996). "Motor neurons in Cu/Zn superoxide dismutase-deficient mice develop normally but exhibit enhanced cell death after axonal injury". Nat Genet 13 (1): 43-7. PMID 8673102.
  66. ^ Van Camp W, Inzé D, Van Montagu M (1997). "The regulation and function of tobacco superoxide dismutases". Free Radic Biol Med 23 (3): 515-20. PMID 9214590.
  67. ^ Chelikani P, Fita I, Loewen P (2004). "Diversity of structures and properties among catalases". Cell Mol Life Sci 61 (2): 192–208. PMID 14745498.
  68. ^ Zámocký M, Koller F (1999). "Understanding the structure and function of catalases: clues from molecular evolution and in vitro mutagenesis". Prog Biophys Mol Biol 72 (1): 19–66. PMID 10446501.
  69. ^ del Río L, Sandalio L, Palma J, Bueno P, Corpas F (1992). "Metabolism of oxygen radicals in peroxisomes and cellular implications". Free Radic Biol Med 13 (5): 557-80. PMID 1334030.
  70. ^ Hiner A, Raven E, Thorneley R, García-Cánovas F, Rodríguez-López J (2002). "Mechanisms of compound I formation in heme peroxidases". J Inorg Biochem 91 (1): 27–34. PMID 12121759.
  71. ^ Mueller S, Riedel H, Stremmel W (1997). "Direct evidence for catalase as the predominant H2O2 -removing enzyme in human erythrocytes". Blood 90 (12): 4973–8. PMID 9389716.
  72. ^ Ogata M (1991). "Acatalasemia". Hum Genet 86 (4): 331-40. PMID 1999334.
  73. ^ Parsonage D, Youngblood D, Sarma G, Wood Z, Karplus P, Poole L (2005). "Analysis of the link between enzymatic activity and oligomeric state in AhpC, a bacterial peroxiredoxin". Biochemistry 44 (31): 10583-92. PMID 16060667. PDB 1YEX
  74. ^ Rhee S, Chae H, Kim K (2005). "Peroxiredoxins: a historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling". Free Radic Biol Med 38 (12): 1543–52. PMID 15917183.
  75. ^ Wood Z, Schröder E, Robin Harris J, Poole L (2003). "Structure, mechanism and regulation of peroxiredoxins". Trends Biochem Sci 28 (1): 32–40. PMID 12517450.
  76. ^ Claiborne A, Yeh J, Mallett T, Luba J, Crane E, Charrier V, Parsonage D (1999). "Protein-sulfenic acids: diverse roles for an unlikely player in enzyme catalysis and redox regulation". Biochemistry 38 (47): 15407-16. PMID 10569923.
  77. ^ Neumann C, Krause D, Carman C, Das S, Dubey D, Abraham J, Bronson R, Fujiwara Y, Orkin S, Van Etten R (2003). "Essential role for the peroxiredoxin Prdx1 in erythrocyte antioxidant defence and tumour suppression". Nature 424 (6948): 561-5. PMID 12891360.
  78. ^ Lee T, Kim S, Yu S, Kim S, Park D, Moon H, Dho S, Kwon K, Kwon H, Han Y, Jeong S, Kang S, Shin H, Lee K, Rhee S, Yu D (2003). "Peroxiredoxin II is essential for sustaining life span of erythrocytes in mice". Blood 101 (12): 5033–8. PMID 12586629.
  79. ^ Dietz K, Jacob S, Oelze M, Laxa M, Tognetti V, de Miranda S, Baier M, Finkemeier I (2006). "The function of peroxiredoxins in plant organelle redox metabolism". J Exp Bot 57 (8): 1697-709. PMID 16606633.
  80. ^ Nordberg J, Arner ES (2001). "Reactive oxygen species, antioxidants, and the mammalian thioredoxin system". Free Radic Biol Med 31 (11): 1287-312. PMID 11728801.
  81. ^ Vieira Dos Santos C, Rey P (2006). "Plant thioredoxins are key actors in the oxidative stress response". Trends Plant Sci 11 (7): 329-34. PMID 16782394.
  82. ^ Arnér E, Holmgren A (2000). "Physiological functions of thioredoxin and thioredoxin reductase". Eur J Biochem 267 (20): 6102–9. PMID 11012661.
  83. ^ Mustacich D, Powis G (2000). "Thioredoxin reductase". Biochem J 346 Pt 1: 1–8. PMID 10657232.
  84. ^ Creissen G, Broadbent P, Stevens R, Wellburn A, Mullineaux P (1996). "Manipulation of glutathione metabolism in transgenic plants". Biochem Soc Trans 24 (2): 465-9. PMID 8736785.
  85. ^ Brigelius-Flohé R (1999). "Tissue-specific functions of individual glutathione peroxidases". Free Radic Biol Med 27 (9–10): 951-65. PMID 10569628.
  86. ^ Ho Y, Magnenat J, Bronson R, Cao J, Gargano M, Sugawara M, Funk C (1997). "Mice deficient in cellular glutathione peroxidase develop normally and show no increased sensitivity to hyperoxia". J Biol Chem 272 (26): 16644-51. PMID 9195979.
  87. ^ de Haan J, Bladier C, Griffiths P, Kelner M, O'Shea R, Cheung N, Bronson R, Silvestro M, Wild S, Zheng S, Beart P, Hertzog P, Kola I (1998). "Mice with a homozygous null mutation for the most abundant glutathione peroxidase, Gpx1, show increased susceptibility to the oxidative stress-inducing agents paraquat and hydrogen peroxide". J Biol Chem 273 (35): 22528-36. PMID 9712879.
  88. ^ Sharma R, Yang Y, Sharma A, Awasthi S, Awasthi Y (2004). "Antioxidant role of glutathione S-transferases: protection against oxidant toxicity and regulation of stress-mediated apoptosis". Antioxid Redox Signal 6 (2): 289–300. PMID 15025930.
  89. ^ Hayes J, Flanagan J, Jowsey I (2005). "Glutathione transferases". Annu Rev Pharmacol Toxicol 45: 51–88. PMID 15822171.
  90. ^ Christen Y (2000). "Oxidative stress and Alzheimer disease". Am J Clin Nutr 71 (2): 621S-629S. PMID 10681270.
  91. ^ Nunomura A, Castellani R, Zhu X, Moreira P, Perry G, Smith M (2006). "Involvement of oxidative stress in Alzheimer disease". J Neuropathol Exp Neurol 65 (7): 631-41. PMID 16825950.
  92. ^ Wood-Kaczmar A, Gandhi S, Wood N (2006). "Understanding the molecular causes of Parkinson's disease". Trends Mol Med 12 (11): 521-8. PMID 17027339.
  93. ^ Davì G, Falco A, Patrono C (2005). "Lipid peroxidation in diabetes mellitus". Antioxid Redox Signal 7 (1–2): 256-68. PMID 15650413.
  94. ^ Giugliano D, Ceriello A, Paolisso G (1996). "Oxidative stress and diabetic vascular complications". Diabetes Care 19 (3): 257-67. PMID 8742574.
  95. ^ Hitchon C, El-Gabalawy H (2004). "Oxidation in rheumatoid arthritis". Arthritis Res Ther 6 (6): 265-78. PMID 15535839.
  96. ^ Cookson M, Shaw P (1999). "Oxidative stress and motor neurone disease". Brain Pathol 9 (1): 165-86. PMID 9989458.
  97. ^ Valko M, Leibfritz D, Moncol J, Cronin M, Mazur M, Telser J (2007). "Free radicals and antioxidants in normal physiological functions and human disease". Int J Biochem Cell Biol 39 (1): 44–84. PMID 16978905.
  98. ^ Van Gaal L, Mertens I, De Block C (2006). "Mechanisms linking obesity with cardiovascular disease". Nature 444 (7121): 875-80. PMID 17167476.
  99. ^ Aviram M (2000). "Review of human studies on oxidative damage and antioxidant protection related to cardiovascular diseases". Free Radic Res 33 Suppl: S85–97. PMID 11191279.
  100. ^ G. López-Lluch, N. Hunt, B. Jones, M. Zhu, H. Jamieson, S. Hilmer, M. V. Cascajo, J. Allard, D. K. Ingram, P. Navas, and R. de Cabo (2006). "Calorie restriction induces mitochondrial biogenesis and bioenergetic efficiency". Proc Natl Acad Sci U S A 103 (6): 1768 – 1773. doi:10.1073/pnas.0510452103. PMID 16446459.
  101. ^ Larsen P (1993). "Aging and resistance to oxidative damage in Caenorhabditis elegans". Proc Natl Acad Sci U S A 90 (19): 8905–9. PMID 8415630.
  102. ^ Helfand S, Rogina B (2003). "Genetics of aging in the fruit fly, Drosophila melanogaster". Annu Rev Genet 37: 329-48. PMID 14616064.
  103. ^ Sohal R, Mockett R, Orr W (2002). "Mechanisms of aging: an appraisal of the oxidative stress hypothesis". Free Radic Biol Med 33 (5): 575-86. PMID 12208343.
  104. ^ Sohal R (2002). "Role of oxidative stress and protein oxidation in the aging process". Free Radic Biol Med 33 (1): 37–44. PMID 12086680.
  105. ^ Rattan S (2006). "Theories of biological aging: genes, proteins, and free radicals". Free Radic Res 40 (12): 1230–8. PMID 17090411.
  106. ^ Thomas D (2004). "Vitamins in health and aging". Clin Geriatr Med 20 (2): 259-74. PMID 15182881.
  107. ^ Ward J (1998). "Should antioxidant vitamins be routinely recommended for older people?". Drugs Aging 12 (3): 169-75. PMID 9534018.
  108. ^ Reiter R (1995). "Oxidative processes and antioxidative defense mechanisms in the aging brain". FASEB J 9 (7): 526-33. PMID 7737461.
  109. ^ Warner D, Sheng H, Batinić-Haberle I (2004). "Oxidants, antioxidants and the ischemic brain". J Exp Biol 207 (Pt 18): 3221–31. PMID 15299043.
  110. ^ Wilson J, Gelb A (2002). "Free radicals, antioxidants, and neurologic injury: possible relationship to cerebral protection by anesthetics". J Neurosurg Anesthesiol 14 (1): 66–79. PMID 11773828.
  111. ^ Lees K, Davalos A, Davis S, Diener H, Grotta J, Lyden P, Shuaib A, Ashwood T, Hardemark H, Wasiewski W, Emeribe U, Zivin J (2006). "Additional outcomes and subgroup analyses of NXY-059 for acute ischemic stroke in the SAINT I trial". Stroke 37 (12): 2970–8. PMID 17068304.
  112. ^ Lees K, Zivin J, Ashwood T, Davalos A, Davis S, Diener H, Grotta J, Lyden P, Shuaib A, Hårdemark H, Wasiewski W (2006). "NXY-059 for acute ischemic stroke". N Engl J Med 354 (6): 588–600. PMID 16467546.
  113. ^ Yamaguchi T, Sano K, Takakura K, Saito I, Shinohara Y, Asano T, Yasuhara H (1998). "Ebselen in acute ischemic stroke: a placebo-controlled, double-blind clinical trial. Ebselen Study Group". Stroke 29 (1): 12-7. PMID 9445321.
  114. ^ Di Matteo V, Esposito E (2003). "Biochemical and therapeutic effects of antioxidants in the treatment of Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis". Curr Drug Targets CNS Neurol Disord 2 (2): 95–107. PMID 12769802.
  115. ^ Rao A, Balachandran B (2002). "Role of oxidative stress and antioxidants in neurodegenerative diseases". Nutr Neurosci 5 (5): 291–309. PMID 12385592.
  116. ^ a b c Stanner SA, Hughes J, Kelly CN, Buttriss J (2004). "A review of the epidemiological evidence for the 'antioxidant hypothesis'". Public Health Nutr 7 (3): 407-22. PMID 15153272.
  117. ^ Bartlett H, Eperjesi F (2003). "Age-related macular degeneration and nutritional supplementation: a review of randomised controlled trials". Ophthalmic Physiol Opt 23 (5): 383-99. PMID 12950886.
  118. ^ Wintergerst E, Maggini S, Hornig D (2006). "Immune-enhancing role of vitamin C and zinc and effect on clinical conditions". Ann Nutr Metab 50 (2): 85–94. PMID 16373990.
  119. ^ Wang J, Wen L, Huang Y, Chen Y, Ku M (2006). "Dual effects of antioxidants in neurodegeneration: direct neuroprotection against oxidative stress and indirect protection via suppression of glia-mediated inflammation". Curr Pharm Des 12 (27): 3521–33. PMID 17017945.
  120. ^ Bleys J, Miller E, Pastor-Barriuso R, Appel L, Guallar E (2006). "Vitamin-mineral supplementation and the progression of atherosclerosis: a meta-analysis of randomized controlled trials". Am. J. Clin. Nutr. 84 (4): 880–7; quiz 954-5. PMID 17023716.
  121. ^ Cook NR, Albert CM, Gaziano JM, et al (2007). "A randomized factorial trial of vitamins C and E and beta carotene in the secondary prevention of cardiovascular events in women: results from the Women's Antioxidant Cardiovascular Study". Arch. Intern. Med. 167 (15): 1610–8. PMID 17698683.
  122. ^ Cherubini A, Vigna G, Zuliani G, Ruggiero C, Senin U, Fellin R (2005). "Role of antioxidants in atherosclerosis: epidemiological and clinical update". Curr Pharm Des 11 (16): 2017–32. PMID 15974956.
  123. ^ Rimm EB, Stampfer MJ, Ascherio A, Giovannucci E, Colditz GA, Willett WC (1993). "Vitamin E consumption and the risk of coronary heart disease in men". N Engl J Med 328 (20): 1450–6. PMID 8479464.
  124. ^ Vivekananthan DP, Penn MS, Sapp SK, Hsu A, Topol EJ (2003). "Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials". Lancet 361 (9374): 2017–23. PMID 12814711.
  125. ^ Roberts LJ, Oates JA, Linton MF, et al (2007). "The relationship between dose of vitamin E and suppression of oxidative stress in humans". Free Radic. Biol. Med. 43 (10): 1388–93. PMID 17936185.
  126. ^ a b Hercberg S, Galan P, Preziosi P, Bertrais S, Mennen L, Malvy D, Roussel AM, Favier A, Briancon S (2004). "The SU.VI.MAX Study: a randomized, placebo-controlled trial of the health effects of antioxidant vitamins and minerals". Arch Intern Med 164 (21): 2335–42. PMID 15557412.
  127. ^ Radimer K, Bindewald B, Hughes J, Ervin B, Swanson C, Picciano M (2004). "Dietary supplement use by US adults: data from the National Health and Nutrition Examination Survey, 1999–2000". Am J Epidemiol 160 (4): 339-49. PMID 15286019.
  128. ^ a b Shenkin A (2006). "The key role of micronutrients". Clin Nutr 25 (1): 1–13. PMID 16376462.
  129. ^ Woodside J, McCall D, McGartland C, Young I (2005). "Micronutrients: dietary intake v. supplement use". Proc Nutr Soc 64 (4): 543-53. PMID 16313697.
  130. ^ Schulz TJ, Zarse K, Voigt A, Urban N, Birringer M, Ristow M (2007). "Glucose Restriction Extends Caenorhabditis elegans Life Span by Inducing Mitochondrial Respiration and Increasing Oxidative Stress". Cell Metab. 6 (4): 280–93. PMID 17908557.
  131. ^ Barros MH, Bandy B, Tahara EB, Kowaltowski AJ (2004). "Higher respiratory activity decreases mitochondrial reactive oxygen release and increases life span in Saccharomyces cerevisiae". J. Biol. Chem. 279 (48): 49883–8. PMID 15383542.
  132. ^ Sohal R, Mockett R, Orr W (2002). "Mechanisms of aging: an appraisal of the oxidative stress hypothesis". Free Radic Biol Med 33 (5): 575-86. PMID 12208343.
  133. ^ Sohal R (2002). "Role of oxidative stress and protein oxidation in the aging process". Free Radic Biol Med 33 (1): 37-44. PMID 12086680.
  134. ^ Rattan S (2006). "Theories of biological aging: genes, proteins, and free radicals". Free Radic Res 40 (12): 1230-8. PMID 17090411.
  135. ^ Dekkers J, van Doornen L, Kemper H (1996). "The role of antioxidant vitamins and enzymes in the prevention of exercise-induced muscle damage". Sports Med 21 (3): 213-38. PMID 8776010.
  136. ^ Tiidus P (1998). "Radical species in inflammation and overtraining". Can J Physiol Pharmacol 76 (5): 533-8. PMID 9839079.
  137. ^ Leeuwenburgh C, Fiebig R, Chandwaney R, Ji L (1994). "Aging and exercise training in skeletal muscle: responses of glutathione and antioxidant enzyme systems". Am J Physiol 267 (2 Pt 2): R439-45. PMID 8067452.
  138. ^ Leeuwenburgh C, Heinecke J (2001). "Oxidative stress and antioxidants in exercise". Curr Med Chem 8 (7): 829-38. PMID 11375753.
  139. ^ Takanami Y, Iwane H, Kawai Y, Shimomitsu T (2000). "Vitamin E supplementation and endurance exercise: are there benefits?". Sports Med 29 (2): 73–83. PMID 10701711.
  140. ^ Mastaloudis A, Traber M, Carstensen K, Widrick J (2006). "Antioxidants did not prevent muscle damage in response to an ultramarathon run". Med Sci Sports Exerc 38 (1): 72–80. PMID 16394956.
  141. ^ Peake J (2003). "Vitamin C: effects of exercise and requirements with training". Int J Sport Nutr Exerc Metab 13 (2): 125-51. PMID 12945825.
  142. ^ Jakeman P, Maxwell S (1993). "Effect of antioxidant vitamin supplementation on muscle function after eccentric exercise". Eur J Appl Physiol Occup Physiol 67 (5): 426-30. PMID 8299614.
  143. ^ Close G, Ashton T, Cable T, Doran D, Holloway C, McArdle F, MacLaren D (2006). "Ascorbic acid supplementation does not attenuate post-exercise muscle soreness following muscle-damaging exercise but may delay the recovery process". Br J Nutr 95 (5): 976-81. PMID 16611389.
  144. ^ Hurrell R (2003). "Influence of vegetable protein sources on trace element and mineral bioavailability". J Nutr 133 (9): 2973S-7S. PMID 12949395.
  145. ^ Hunt J (2003). "Bioavailability of iron, zinc, and other trace minerals from vegetarian diets". Am J Clin Nutr 78 (3 Suppl): 633S-639S. PMID 12936958.
  146. ^ Gibson R, Perlas L, Hotz C (2006). "Improving the bioavailability of nutrients in plant foods at the household level". Proc Nutr Soc 65 (2): 160-8. PMID 16672077.
  147. ^ a b Mosha T, Gaga H, Pace R, Laswai H, Mtebe K (1995). "Effect of blanching on the content of antinutritional factors in selected vegetables". Plant Foods Hum Nutr 47 (4): 361-7. PMID 8577655.
  148. ^ Sandberg A (2002). "Bioavailability of minerals in legumes". Br J Nutr 88 Suppl 3: S281-5. PMID 12498628.
  149. ^ a b Beecher G (2003). "Overview of dietary flavonoids: nomenclature, occurrence and intake". J Nutr 133 (10): 3248S-3254S. PMID 14519822.
  150. ^ Prashar A, Locke I, Evans C (2006). "Cytotoxicity of clove (Syzygium aromaticum) oil and its major components to human skin cells". Cell Prolif 39 (4): 241-8. PMID 16872360.
  151. ^ Hornig D, Vuilleumier J, Hartmann D (1980). "Absorption of large, single, oral intakes of ascorbic acid". Int J Vitam Nutr Res 50 (3): 309-14. PMID 7429760.
  152. ^ Omenn G, Goodman G, Thornquist M, Balmes J, Cullen M, Glass A, Keogh J, Meyskens F, Valanis B, Williams J, Barnhart S, Cherniack M, Brodkin C, Hammar S (1996). "Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial". J Natl Cancer Inst 88 (21): 1550–9. PMID 8901853.
  153. ^ Albanes D (1999). "Beta-carotene and lung cancer: a case study". Am J Clin Nutr 69 (6): 1345S-1350S. PMID 10359235.
  154. ^ a b Bjelakovic G, Nikolova D, Gluud L, Simonetti R, 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. PMID 17327526.
  155. ^ Study Citing Antioxidant Vitamin Risks Based On Flawed Methodology, Experts Argue News release from Oregon State University published on ScienceDaily, Accessed 19 April 2007
  156. ^ Miller E, Pastor-Barriuso R, Dalal D, Riemersma R, Appel L, Guallar E (2005). "Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality". Ann Intern Med 142 (1): 37–46. PMID 15537682.
  157. ^ Bjelakovic G, Nagorni A, Nikolova D, Simonetti R, Bjelakovic M, Gluud C (2006). "Meta-analysis: antioxidant supplements for primary and secondary prevention of colorectal adenoma". Aliment Pharmacol Ther 24 (2): 281-91. PMID 16842454.
  158. ^ Caraballoso M, Sacristan M, Serra C, Bonfill X (2003). "Drugs for preventing lung cancer in healthy people". Cochrane Database Syst Rev: CD002141. PMID 12804424.
  159. ^ Bjelakovic G, Nagorni A, Nikolova D, Simonetti R, Bjelakovic M, Gluud C (2006). "Meta-analysis: antioxidant supplements for primary and secondary prevention of colorectal adenoma". Aliment. Pharmacol. Ther. 24 (2): 281-91. PMID 16842454.
  160. ^ Coulter I, Hardy M, Morton S, Hilton L, Tu W, Valentine D, Shekelle P (2006). "Antioxidants vitamin C and vitamin e for the prevention and treatment of cancer". Journal of general internal medicine: official journal of the Society for Research and Education in Primary Care Internal Medicine 21 (7): 735-44. PMID 16808775.
  161. ^ Schumacker P (2006). "Reactive oxygen species in cancer cells: Live by the sword, die by the sword.". Cancer Cell 10 (3): 175-6. PMID 16959608.
  162. ^ Seifried H, McDonald S, Anderson D, Greenwald P, Milner J (2003). "The antioxidant conundrum in cancer". Cancer Res 63 (15): 4295–8. PMID 12907593.
  163. ^ Simone C, Simone N, Simone V, Simone C (2007). "Antioxidants and other nutrients do not interfere with chemotherapy or radiation therapy and can increase kill and increase survival, part 1". Alternative therapies in health and medicine 13 (1): 22-8. PMID 17283738.
  164. ^ Moss R (2006). "Should patients undergoing chemotherapy and radiotherapy be prescribed antioxidants?". Integrative cancer therapies 5 (1): 63–82. PMID 16484715.
  165. ^ Cao G, Alessio H, Cutler R (1993). "Oxygen-radical absorbance capacity assay for antioxidants". Free Radic Biol Med 14 (3): 303-11. PMID 8458588.
  166. ^ Ou B, Hampsch-Woodill M, Prior R (2001). "Development and validation of an improved oxygen radical absorbance capacity assay using fluorescein as the fluorescent probe". J Agric Food Chem 49 (10): 4619–26. PMID 11599998.
  167. ^ Prior R, Wu X, Schaich K (2005). "Standardized methods for the determination of antioxidant capacity and phenolics in foods and dietary supplements". J Agric Food Chem 53 (10): 4290-302. PMID 15884874.
  168. ^ Cao G, Prior R (1998). "Comparison of different analytical methods for assessing total antioxidant capacity of human serum". Clin Chem 44 (6 Pt 1): 1309–15. PMID 9625058.
  169. ^ Xianquan S, Shi J, Kakuda Y, Yueming J (2005). "Stability of lycopene during food processing and storage". J Med Food 8 (4): 413-22. PMID 16379550.
  170. ^ Rodriguez-Amaya D (2003). "Food carotenoids: analysis, composition and alterations during storage and processing of foods". Forum Nutr 56: 35-7. PMID 15806788.
  171. ^ Baublis A, Lu C, Clydesdale F, Decker E (2000). "Potential of wheat-based breakfast cereals as a source of dietary antioxidants". J Am Coll Nutr 19 (3 Suppl): 308S-311S. PMID 10875602.
  172. ^ Rietveld A, Wiseman S (2003). "Antioxidant effects of tea: evidence from human clinical trials". J Nutr 133 (10): 3285S-3292S. PMID 14519827.
  173. ^ Henry C, Heppell N (2002). "Nutritional losses and gains during processing: future problems and issues". Proc Nutr Soc 61 (1): 145-8. PMID 12002789.
  174. ^ Antioxidants and Cancer Prevention: Fact Sheet. National Cancer Institute. Retrieved on 2007-02-27.
  175. ^ Witschi A, Reddy S, Stofer B, Lauterburg B (1992). "The systemic availability of oral glutathione". Eur J Clin Pharmacol 43 (6): 667-9. PMID 1362956.
  176. ^ Kader A, Zagory D, Kerbel E (1989). "Modified atmosphere packaging of fruits and vegetables". Crit Rev Food Sci Nutr 28 (1): 1–30. PMID 2647417.
  177. ^ Zallen E, Hitchcock M, Goertz G (1975). "Chilled food systems. Effects of chilled holding on quality of beef loaves". J Am Diet Assoc 67 (6): 552-7. PMID 1184900.
  178. ^ Iverson F (1995). "Phenolic antioxidants: Health Protection Branch studies on butylated hydroxyanisole". Cancer Lett 93 (1): 49–54. PMID 7600543.
  179. ^ E number index. UK food guide. Retrieved on 2007-03-05.
  180. ^ Robards K, Kerr A, Patsalides E (1988). "Rancidity and its measurement in edible oils and snack foods. A review". Analyst 113 (2): 213-24. PMID 3288002.
  181. ^ Del Carlo M, Sacchetti G, Di Mattia C, Compagnone D, Mastrocola D, Liberatore L, Cichelli A (2004). "Contribution of the phenolic fraction to the antioxidant activity and oxidative stability of olive oil". J Agric Food Chem 52 (13): 4072–9. PMID 15212450.
  182. ^ CE Boozer, GS Hammond, CE Hamilton (1955) "Air Oxidation of Hydrocarbons. The Stoichiometry and Fate of Inhibitors in Benzene and Chlorobenzene". Journal of the American Chemical Society, 3233–3235
  183. ^ Why use Antioxidants?. SpecialChem Adhesives. Retrieved on 2007-02-27.
  184. ^ a b Fuel antioxidants. Innospec Chemicals. Retrieved on 2007-02-27.
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Antioxidant". A list of authors is available in Wikipedia.
Your browser is not current. Microsoft Internet Explorer 6.0 does not support some functions on Chemie.DE