ANTIOXIDANTS (synonym: antioxidants, anti-oxygenes) — the substances of various chemical nature capable to brake or eliminate non-enzymatic free radical oxidation of organic matters with molecular oxygen. Are widely used in the industry for increase in shelf-lifes of various substances subject to oxidation.
And., (bioantioxidants) functioning in a live organism, play an important role, protecting from non-enzymatic autooxidation biological substrates, napr, the easily oxidized lipids and, in particular, fats and fatty acids of membrane formations of a cell. Bioantioxidants are necessary components of all fabrics and cells of live organisms where they in normal physiological concentrations support free radical autooxidizing processes on low stationary level. The expenditure and replenishment are normal And. in fabrics of live organisms it is balanced.
Bioantioxidants are, as a rule, multifunctional connections which anti-oxidizing function is expressed in different degree. In this regard distinguish antioxidants — connections which main biological function is defined or it is connected with anti-oxidizing activity, napr, tokoferola, and the substances possessing anti-oxidizing action which main biological function is not connected with anti-oxidizing properties. The antibiotics possessing first of all bactericidal action, but showing also aitiokislitelny properties concern to the last, e.g.
Individual bioantioxidants create the system defining anti-oxidizing activity of living tissues.
In parallel there are three classifications And., constructed on the different principles: 1) by origin, 2) to chemical constitution and 3) to the mechanism of action.
By origin And. in the most habit view are divided into natural (bioantioxidants) and synthetic.
The accounting of number of aromatic rings in structure of the chemical connection having anti-oxidizing activity and the number of deputies in a ring is the basis for chemical classification. However this classification far does not cover all variety of connections with anti-oxidizing properties.
On the third type of classification to And. carry actually And., synergists (i.e. substances which poorly or at all without slowing down oxidation, strengthen action true And.) and group of connections with the mixed properties.
belong To number of the most effective and eurysynusic bioantioxidants first of all tokoferola (vitamin E), a number of phenols (eugenol and its derivatives) and polyphenols (konidendrin, pirokakhetin, derivatives gallic to - you, etc.), flavonoids (Rutinum, meletin), ubikhinona, some steroid hormones, phospholipids, including lecithin and kephalin. Here it is necessary to carry also ascorbic, lemon, nicotinic, degidrokofeinovy and benzoic acids and their salts, sulfur-containing amino acids (cysteine, glutathione), serotonin, adrenaline, bilirubin, some antibiotics etc.
From synthetic antioxidants in the industry, biology and medicine numerous connections of the phenolic nature are used (butyl hydroxyanisol, butyl oxytoluene-ionol), naphthols, organic compounds are gray and first of all aminothiols (beta mercaptoethylamine, beta mercaptopropylamine), derivatives barbituric to - you etc.
Now many are synthesized natural And. (tocopherol, derivatives gallic to - you, etc.) also their industrial production is arranged.
The mechanism of action
Primary mechanism of effect of antioxidants consists in interaction:
a) with active radicals (R ·, ROO ·),
b) with hydroperoxides (ROOH),
c) in blocking of catalysts of free radical oxidation, first of all ions of metals of variable valency.
Anti-oxidizing activity of the majority of individual connections is defined by existence at them mobile hydrogen atom. Molecule such And. present in the form And — N where H — mobile hydrogen atom which determines interaction of Ampere-second by radicals by the scheme:
ROO · + A — N → ROOH + A'
R · + A — H → RH + A'.
There is a replacement of active radicals of substrate (ROO ·, R ·) on a low-active radical of antioxidant A' which is not capable to continuation of a chain and turns into stable molecular products due to polymerization (see):
And' + And' → And — A
A' + R · → A — R.
K A., reacting with hydroperoxides, sulfur-containing connections belong. Decomposing hydroperoxides, they exclude a possibility of dissociation of hydroperoxide on two active radicals which could begin a chain of new oxidation reactions. The similar mechanism is developed on the example of dialkylsulfides (R — S — R):
Reduction of catalytic influence of ions of metals of variable valency (e.g., ions of iron, a cut in various connections can be two - or trivalent) happens due to ability of a number of substances (e.g., lemon to - that, cyanic connections, etc.) to connect these ions in complex connections.
Free radical oxidation, though with very small speed, continuously proceeds normal in fabrics of a live organism with formation of active products: free radicals (see), peroxide radicals, hydroperoxides, aldehydes, ketones is also followed by radical polymerization.
All-biological justification of a role of antioxidants as protective preventive and remedy at morbid conditions with sharp strengthening of free radical oxidation was for the first time given on the example of radiation injury (B. N. Tarusov, 1954). Toxic action of products of free radical oxidation is shown in an inactivation of sulphhydryl groups of proteins, activation of lipases, emergence in cells of large drops of fat, dissociation and suppression of oxidizing phosphorylation, deformation, swelling, adhesion, and in certain cases and in final fracture of mitochondrions, in aberation chromosomes, in activation of autolytic processes. There is a nonspecific disturbance of integrity p functioning of biological membranes (see Membranes biological) and as a result disturbance of cellular metabolism, and also process of cell fission. On the whole organism reduction of body weight is observed, slackness, weakening of reaction to external irritants, an ulceration of a mucous membrane of eyes, a nose, anemia, disorder of function went. - kish. a path, arrhythmia of breath, a leukopenia, dominance of dystrophic processes over regenerative etc.
Bioantiokisliteli regulate extent of influence of free radical oxidation in the majority of metabolic processes. The final result of effect of bioantioxidants is creation of optimal conditions for metabolism and ensuring normal growth of cells and fabrics.
General or local change of contents And. in fabrics of a live organism it is, as a rule, connected with changes of intensity of metabolism and a condition of an organism. It is possible to allocate several main types of change of level of bioantioxidants.
Decrease in level of bioantioxidants
Long decrease or total disappearance in fabrics of some bioantioxidants happens at avitaminosis E, and also at avitaminosis of C, P, K. At these morbid conditions resistance to such factors as ionizing radiation or poisoning with oxygen activating radical oxidation sharply decreases. Anti-oxidizing action serves, obviously, to one of the main properties of tokoferol (see) defining their biological functions. Accumulation of lipidic peroxides in tissues of animals on initial phases of E-avitaminosis and a community of symptoms of E-avitaminosis with the symptoms arising during the feeding by an animal of oxidates of fats and also decrease in level of lipidic peroxides and removal of the main symptoms of E-avitaminosis introduction of some connections (e.g., difenilparafenilendiamin) testifies at which the general with tocopherol are only anti-oxidizing properties to it.
Long decrease in total anti-oxidizing activity of fabrics of a live organism happens at radiation injury.
Constant, though insignificant, decrease in anti-oxidizing activity of lipids of muscular tissue happens during the aging.
The general for the studied cases of considerable or long lowering of the level of bioantioxidants in fabrics of a live organism is disturbance of normal metabolism and as a result of it decrease in growth rates, weakening of regenerative and proliferative processes, and also decrease in adaptation opportunities of an organism.
Increase in level of bioantioxidants
In experiences short-term artificial increase in contents in an organism of antioxidants (due to introduction to mice in nontoxic concentration of glutathione, thiourea, a betaaminoetilizotiuroniya, propyl gallate, nordihydroguaiaretic to - you) gave unambiguous effect — increased resistance of animals to poisoning with oxygen.
The majority of radio protective agents (see. Radioprotectors ) has anti-oxidizing properties. Introduction them in an organism increases anti-oxidizing activity of fabrics and increases resistance of animals to action of ionizing radiation.
The increased level of anti-oxidizing activity of lipids of a number of tumors is found in the period of the maximum growth rate of these tumors. At the same time in tumors accumulation of one of the strongest bioantioxidants — tocopherol is noted.
Short-term increase in anti-oxidizing activity is followed by usually general activation of metabolism with strengthening of proliferative processes and increase in adaptation opportunities of an organism. Long increase in level of bioantioxidants is followed by disturbance of normal metabolism and is observed with a malignant growth.
Constancy of level of total anti-oxidizing activity of fabrics, identity of this level for each body serve, obviously, to one of the main indicators of a homeostasis (see. Homeostasis ). The available experimental data show that considerable and long change of anti-oxidizing activity both towards increase, and towards decrease is led to pathological changes in an organism.
Methodical bases of definition of anti-oxidizing effect of fabrics, aqueous and lipidic extracts and individual connections at their introduction to an organism or to model systems are under construction: 1) on definition of reduction of amount of the formed peroxides at presence And. in comparison with control; 2) on change of breakdown rate of some connections by products of free radical oxidation [e.g., dioxyphenylalanine (DOFA) at oxidation forms products with other properties]; 3) on increase in time (induction period), during to-rogo a certain amount of peroxides is formed; 4) on change of intensity of chemiluminescence; 5) on reduction of volume of radical copolymerization; 6) on reduction of toxicity of the oxidized samples; 7) on registration by method of an electronic paramagnetic resonance (see) loudspeakers of accumulation of rather stable radicals And'.
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