TOKOFEROLA — group of the methyl derivatives of a tokol possessing biol. activity of vitamin E. The term «tokoferola» is not a synonym of the term «vitamin E» since biol. activity of vitamin E, but less expressed also tokotriyenola possess. T. carry out in fabrics a role biol. antioxidants (see. Antioxidants ), inactivating free radicals (see. Radicals free ) and by that the free radical processes of peroxide oxidation interfering development (see. Peroxides ) unsaturated lipids — the major component biol. membranes (see. Membranes biological ). This function T. is of great importance for maintenance of structural integrity and functional activity of membranes of cells and subcellular organellas. Insufficiency of T. in a human body leads to the hypovitaminosis E which is shown muscular weakness and hypotonia up to muscular dystrophy, bent to misbirths (see), a scleroderma (see), etc. (see. Vitamin deficiency). Drugs T. use as pharmaceuticals at a hypovitaminosis E and other diseases.
Basis of all T. is tokol [2-methyl-2 (4', 8', 12 '-trimetiltridetsil) - chroman-6-ol], i.e. 6-oksikhroman, replaced in situation 2 with methyl group (CH 3 - group) and having a side saturated izoprenoidny chain from 16 carbon atoms.
Separate T. — α-, β-, γ-and δ-tokoferola — differ from each other in quantity and position of methyl groups in an aromatic ring of a molecule of a 6-oksikhroman. The most important of them in biol. the relation, alpha tocopherol, is 5,7,8-trimetiltokoly; beta tocopherol is 5,8-dimetiltokoly, gamma tocopherol — 7,8-dimetiltokoly and delta tocopherol — 8 methyltocopherol.
For a molecule T. three asymmetric centers therefore each of T are characteristic. has 8 stereoisomers (see. Isomerism ) and 4 racemates (see. Racemic connections ). Natural alpha tocopherol has a D-configuration at all asymmetric centers and is designated as D - alpha tocopherol.
All T. at the room temperature represent oils of light yellow color; pier. the weight (weight) of alpha tocopherol 430,7, alpha tocopheryl-acetate — 472,8; t°pl D - alpha-tocopherol 2,5 — 3,5 °, D - alpha-tocopheryl acetate 26,5 — 27,5 °; maxima of absorption for D - alpha-tocopherol and DL - a-tocopherol correspond to the wavelength of 292 nanometers, and for D - alpha tocopheryl acetate and DL - alpha-tocopheryl acetate — the wavelength of 284 — 285 and 285,5 nanometers. T. are water-insoluble, well rastvorima in organic solvents — chloroform, ether, hexane, petroleum ether, it is slightly worse — in acetone and alcohol. Solutions T. in organic solvents possess intensive fluorescence with a maximum of excitement at 295 nanometers. and a maximum of the radiation (issue) at 320 — 340 nanometers also rotate the plane of the polarized light to the right. T. are steady against action to - t and alkalis. In vacuum or the atmosphere of any inert gas T. are stable even during the heating to 100 °. T. are sensitive to the Uv-radiation, oxygen of air and other oxidizers, to-rye turn them into the corresponding quinones deprived biol. activities. T. easily form esters with to-tami; ethers T. differ considerably in bigger oxidation stability. The most important of them — alpha tocopheryl acetate (D - alpha-tocopheryl acetate) and DL - alpha-tocopheryl acetate.
T. easily enter interaction - with free radicals and active forms of oxygen, than their antiokspdantny properties are defined.
In the medical industry natural T. receive from vegetable oils, and synthetic T. — condensation of methyl-substituted n-hydrochinones with phytol or isophytol.
T. are eurysynusic in the nature. In a human body they are present at all fabrics, being found hl. obr. in membranes of cells and subcellular organellas. From foodstuff T are richest. vegetable oils, especially corn and cotton, and also the oil received from wheaten germs (tab). Most part of T. sunflower-seed oil it is the share of α-tocopherol ((((((((((60 — 80%), soy and corn — of γ-tocopherol ((((((((((60 and 80% respectively). Animal products, especially milk, are poor in T.
E.g., its contents in food stuffs express total activity of vitamin E during the calculation in a-tokoferolovykh equivalents, activity of 1 equivalent corresponds to activity of 1 mg of natural α-tocopherol.......... As the last is unstable, as the standard for definition biol. activities recommend to use D-α-токоферилацетат.
Biol. activity of T. measure in the international units (ME); 1 ME corresponds to activity of 1 mg D L-α-токоферилацетата entered by per os to the pregnant rats who are contained on the diet deprived of vitamin E (the test on prevention of a resorption of a fruit). Activity of natural D-α-токоферола, the most active of all T., activities of synthetic DL-α-токоферола are about 40% higher. Biol. activity β-, γ-and δ-tokoferol makes respectively 20 — 30, 10 and 1% of activity of natural D-α-токоферола.
Need of the person for vitamin E is definitely not established; the recommended norm of its consumption accepted in the USSR makes 12 — 15 ME a day. Increase in consumption with food of polyunsaturated fatty acids (see) increases the need of a human body for vitamin E.
One of the main methods of assessment of security of the person with vitamin E is definition of concentration of T. in serum or a blood plasma. Usually for this purpose apply spectrophotometric methods (see. Spektrofotometriya ), the T based on oxidation. ferric chloride and definition of the formed ions of Fe2 + in the form of the painted complex with α-, α '-dipiridilom: or au phenanthroline. The wide spread occurance is got by the spektroflyuorimetrichesky methods having bigger sensitivity and allowing to investigate the maintenance of T. in 0,1 ml of blood serum.
As functional methods of assessment of security of an organism with vitamin E use excretion creatine (see) with urine and sensitivity of erythrocytes to reacid hemolysis in the isotonic environment. Both of these indicators significantly increase at deficit of vitamin E. Besides, by method of gas chromatography (see) determine the content in expired air of a pentane and ethane, quantity to-rykh at deficit of vitamin E increases owing to peroxide oxidation unsaturated fat to - t.
Normal concentration of T. in blood serum makes 0,8 — 1,2 mg / 100 ml. Newborns and especially at premature children have a concentration of T. there are 0,2 — 0,4 mg / 100 ml.
A wedge, manifestations of insufficiency of vitamin E usually find at concentration of T. in blood serum it is lower than 0,5 mg / 100 of ml. A hypovitaminosis E (generally because of insufficiency of T.) occurs at adults quite seldom and it is, as a rule, caused by disturbances of absorption of T. in intestines at to a steatorrhea (see), enterectomies, etc. Endogenous deficit of T. arises at an abetali-poproteinemiya (see) — the hereditary disease which is genetically caused by oppression of synthesis of beta lipoproteids, pre - beta lipoproteids and chylomicrons (see. Lipoproteids ) in a liver.
As T. badly pass through a placental barrier, often observe insufficiency of vitamin E at newborns and especially at the premature children who are on artificial feeding. A hypovitaminosis of E at premature, aggravated by oxygenation. can be the cause of anemia (see), retinopathies (see) and vision disorders (see), a bronchopulmonary dysplasia, sudden death of newborns. As cow's milk is much poorer than T., than women's, that inclusion of T.
in complex therapy premature and enrichment of T. mixes for artificial feeding actions mi for prevention of the specified disturbances are important.
In an experiment on animals it is established. that insufficiency of T. leads to dystrophy of a germinal epithelium of seed bubbles, decrease in mobility of spermatozoa, a resorption of embryos and fruits, encephalopathy, exudative catarrally diathesis, accumulation in fabrics of lipofuscin.
Are the cornerstone of all these manifestations bpokhy. the disturbances caused by loss of specific functions T. in an organism, in particular strengthening of peroxide oxidation of lipids biol. membranes, leading to damage of cellular and subcellular membranes. This defect is the reason of such manifestation of insufficiency of vitamin E as sharp strengthening of sensitivity of erythrocytes to peroxide hemolysis, loss by a sarcoplasmic reticulum of ability to accumulation and deduction of ions of Sa 2+ , leading to disturbances in the mechanism of muscular contraction (see) and to an exit in blood of fabric enzymes.
Tocopherol as drug
as medicine with medical and the preventive purposes is used by the solutions of alpha tocopherol of acetate (vitamin E) in oil (Solutio α-Tocopheroli acetatis oleosa) 5, 10 and 30 of % containing in 1 ml respectively 50, 100 p 300 mg of synthetic α-tocopherol of acetate (α-tocopheryl acetate)))))))))).
Tocopherol acetate well influences functions of skeletal muscles, gonads, a liver, cells of a nervous system, connecting fabric and skin. There are data on indirect influence of tocopherol of acetate on oxygen absorption mitochondrions that defines a role of T. in energy balance. Besides, drug has the regulating effect on biosynthesis of proteins, nucleinic to - t and steroids.
Absorption of tocopherol of acetate at introduction inside happens in a small bowel after emulsification by means of bile acids (see) and juice of a pancreas. Passing through a mucous membrane of intestines, according to the mechanism of passive transport of tocopherol acetate comes to a lymph, contacts lipoproteids and is distributed on various bodies and fabrics unevenly. Nevsosavshiys-ya in intestines of a tokode-rol acetate is removed in not changed look, got into blood — is removed from an organism with urine in the form of water-soluble glucuronides; in rezul to a tata of free radical oxidation of tocopherol of acetate also other metabolites of T can be formed tokoferilkhi-non., brought out of an organism with urine.
Tocopherol acetate is applied at muscular atrophies, a dermatomyositis, an amyotrophic side sclerosis, disturbances of a menstrual cycle, threat of abortion, disturbance of functions of gonads at men, diseases of neuromuscular system and connecting fabric (e.g., at a palmar fibromatosis), atherosclerosis and diseases of peripheral vessels. There are data on effective use of tocopherol of acetate at a nek-ry dermatosis, psoriasis, a lupus erythematosus and other diseases of skin, at a myocardial dystrophy and diseases of a liver. In pediatric practice of tocopherol acetate is applied at a sclerodermitis and a hypotrophy.
Appoint tocopherol acetate inside and intramusculary; at diseases of neuromuscular system appoint 15 — 100 mg a day, at disturbances of a spermatogenesis and potentiality — on 100 — 300 mg a day (in combination with hormonal therapy), at a usual abortion — on 10 — 15 mg a day in the first 2 — 3 months of pregnancy, at the menacing abortion — on 100 — 150 mg a day (in combination with progesterone) within 5 — 7 days, at atherosclerosis and diseases of peripheral vessels — on 100 mg (in combination with Retinolum). To babies and children of younger age appoint 5 — 10 mg of tocopherol of acetate a day. Intramusculary the drug is administered in the warmed-up look daily or every other day in cases of disturbance of absorption and exchange of tocopherol of acetate in an organism. Dosages are same, as well as at intake.
Tocopherol acetate — low-toxic connection. At intramuscular introduction sometimes observe allergic and toxic manifestations, and also pain in the place of an injection. Tocopherol acetate is incompatible with benzylpenicillin. It is necessary to show care at its appointment as the patient with a heavy cardiosclerosis and a myocardial infarction.
Forms of release: in bottles of orange color on 10, 20, 25, 50 ml and the capsular, containing 0,1 or 0,2 ml 50% of solution (0,05 or 0,1 g of tocopherol of acetate). For intramuscular introduction solutions of tocopherol of acetate (Solutio α-Tocopheroli acetatis oleosa pro injectionibus) in ampoules on 1 ml produce oil 5, 10 and 30%.
Store in well corked bottles in the cool, dry, protected from light place.
Table. CONTENTS TOKOFEROLOV (in mg on 100 g) In VEGETABLE OILS AND SOME FOODSTUFF (R. N of Bunnell, 1965; W. H. Sebrell, 1972)
Bibliography: Berezovsky V. M. Chemistry of vitamins, M., 1973; Vitamins, under the editorship of M. I. Smirnov, page 125, M., 1974; M and sh to about in with to and y M. D. Pharmaceuticals, t. 2^ page 37, M., 1984; X and l-muradov A. G., Totsky V. N. and Chagoved R. V. Transport of fat-soluble vitamins, Kiev, 1980; Experimental vitaminology, under the editorship of Yu. M. Ostrovsky, page 18, Minsk, 1979; Yakovlev T. N. Treatment-and-prophylactic vitaminology, L., 1981; Tocopherol, oxvgen and biomembranes, ed. by C. de Duve a. O. Hayaisbi, Amsterdam — N. Y., 1978; The vitamins, chemistry, physiology, pathology, methods, ed. by W. H. Sebrell a. R. O. Harris, v. 5, N. Y., 1972.
V. B. Spirichev; V. M. Avakumov (pharm.).