[Intermolecular interactions of dipeptide triterpene derivatives and natural quinones with alpha-tocopherol]. / Mezhmolekuliarnye vzaimodeistviia dipeptidnykh proizvodnykh triterpenoidov i prirodnykh khinonov s tokoferolom.

In modeling system of the initiated oxidation of methyl oleate the antioxidation activity of a series of dipeptide derivatives of betulonic and glycyrrhetic acids, natural quinones (ubiquinone, philloquinone and menadione) and the kinetic effects of their combined action with alpha-tocopherol were studied. The same extreme character of the dependence of inhibitory action on the concentration of all investigated substances was found. Combined addition of triterpenoids or quinones together with alpha-tocopherol attenuated their effect. The mechanism of intermolecular interactions of tocopherol with quinones and triterpenoids is offered. The biological importance of these effects is discussed.

The role of tocopherols in biomembrane lipid peroxidation.

The rate constants of elementary reactions of oxidation inhibition by tocopherols of different structures (peroxy radical destruction by antioxidant molecules, interaction of inhibitor radicals with one another and with oxidation substrate) are discussed. In contrast with most synthetic phenol antioxidants, tocopherols exhibit a high affinity to peroxy radicals (the rate constants for their reactions with these radicals are one or two orders of magnitude greater than those for reactions involving most synthetic phenols: they possess a fairly high stability of phenoxyl radicals formed and activity in the reaction of oxidation-chain transfer). The activity of tocopherol radicals in chain transfer reactions depends on their structure and manifests itself in a marked dependence of the extent of inhibition on oxidation conditions and the antioxidant concentration, up to an opposite effect. This can be used to control the oxidation rate: the radicals formed from tocopherols can serve as a buffer maintaining the oxidation rate at a certain level in systems with different antioxidant concentrations (concentration control) and with substrates of various unsaturation extent (substrate control). Tocopherols exhibit a unique set of properties which allow them to control the rate of lipid peroxidation and the physico-chemical properties of biological membranes. This dual effect provides the feedback relations and thereby maintains homeostasis in the organism.

Characterization of bilirubin inhibitory properties in free radical oxidation reactions.

The rate constant of the reaction between bilirubin (BR), the end product of heme catabolism, and alkylperoxyl radical was estimated by the chemiluminescence method in the model reaction of ethyl benzene induced oxidation. The constant was determined to be 1.5.10(4) M-1.s-1. The data on the decrease in the absorbance at 450 mn (as a result of BR oxidation) give the same rate constant. A marked antioxidant action of BR, which was comparable to that of ionol (4-methyl-2,6-di-tert-butyl-phenol), was demonstrated in the methyl oleate oxidation model. The results indicate that each molecule of BR breaks more than two chains of oxidation. Oxidation of BR results in the formation of colourless reaction products without significant amounts of biliverdin being formed. BR oxidation products, hypothetically, dipyrrole fragments of the tetrapyrrole BR molecule, also demonstrate the radical trapping activity (the rate constant, 0.5.10(4) M-1.s-1). Our data show that BR is a very efficient peroxyl radical scavenger and can protect membrane lipids from oxidation by these radicals. It is suggested that elevation of the BR level in different physiological and pathological states can be considered to be a protective reaction.

[Antioxidant activity of natural and synthetic quinones]. / Antioksidantnaia aktivnost' prirodnykh i sinteticheskikh khinonov.

Antioxidation activity (AOA) of ubiquinone (Q10), phylloquinone (vitamin K1), menadione as well as of the newly synthesized analogues of vitamin K1--N-derivatives of 2-methyl-3-aminomethyl 1.4-naphthoquinone, producing autocomplexes with intramolecular transfer of electrons, was studied in the model system of the methyl oleate initiated oxidation. The menadione AOA was shown to be 2-fold higher as compared with the inhibitory activity of natural quinones. Activity of AK-40 and AK-49, artificial analogues of vitamin K1, was higher 2.6-fold than that of ubiquinone and phylloquinone and 1.4-fold higher than menadione activity. At the same time, AOA of ubiquinone and phylloquinone was 1.5-fold lower than the tocopherol activity, while naphthoquinones AK-40 and AK-49 were 2-fold more active as compared with tocopherol but their activity was 2-fold lower than ionol. Mechanism of natural and synthetic quinones action as well as properties of their long chain analogues are discussed.

[Synergistic effect of antioxidants and phospholipids during oxidation of natural lipids]. / Sinergicheskii éffekt antioksidantov i fosfolipidov pri okislenii prirodnykh lipidov.

The effect of mixtures of phospholipids (PL) and natural antioxidants (AO)--tocopherol (TP), ubiquinone, ubichromenol, vitamin K, on the value of induction periods and on the rate of initiated oxidation of model substrates (++methyl oleate, mixtures of fatty acid methyl ethers, ethylbenzene) was studied at 60 degrees C. The possibility of synergism of different AO in the presence of PL has been established. It has been shown that the action of bioantioxidants in lipids may be increased 2.5-3.5 times. The dependences of TP and PL synergistic effect values on the concentration of the mixture components were studied. It has been shown that the synergistic++ effect grows proportionally to the amount of TP (in the interval studied up to 5 X 10(-3)M). At a constant concentration of TP the dependence of the value of induction periods increases linearly with the growth of PL concentration at the interval of 0.0-0.2%, and further it does not depend on the amount of PL. It has been shown that the synergism value does not depend on oxidation conditions and the nature of the oxidized substrate.

[The study of the additive antioxidative activity of total natural lipid antioxidants]. / Izuchenie additivnogo antiokislitel'nogo deistviia summy prirodnykh antioksidantov lipidov.

Kinetics of methyl oleate and ethylbenzene oxidation was studied in presence of tocopherol homologues alpha, beta, gamma, delta, tocopherol derivatives C6 and C11, ubichinol QH2-9, which were isolated from natural lipids. Effects of various natural antioxidants in mixtures were interindependent.

[Changes in the physico-chemical characteristics of mouse liver lipids after administration of a mixture of unsaturated fatty acids]. / Izmenenie fiziko-khimicheskikh kharakteristik lipidov pecheni myshei pri vvedenii zhivotnym smesi nenasyshchennykh zhirnykh kislot.

The effects of a mixture of unsaturated fatty acids (UFA) on changes in the lipid oxidation substrate, a system of natural antioxidants and the functioning of a system controlling lipid peroxidation were studied. It was shown that arachidonate induces the incorporation of fatty acids into individual lipid fractions and the dilution of lipids by UFA esters, as a result of which the relative amount of natural antioxidants diminishes. Under these conditions, the oxidative capacity of lipids decreases, which manifests itself in a reduction of the rate of natural antioxidants utilization and an increase in their number. It was shown that purposeful modification of the lipid substrate does not interfere with the interaction between individual parameters of the system controlling lipid peroxidation.

[Relation between activity of antioxidants and oxidation of substrates in natural lipids]. / O vzaimosviazi aktivnosti antioksidantov i okisliaemosti substratov v lipidkh prirodnogo proiskhozhdeniia.

Using chemiluminescence method, the oxidation level of lipids extracted from various organs and tissues of fish Coregonus peled (Gmelin) was investigated. The analysis of interrelation between the oxidation level, quantity and composition of phospholipids (PL), fatty acids (FA), natural antioxidants (NAO) was carried out. The oxidation level of the lipids under investigation is shown to increase in series: first go internal fat lipids, then--lipids of brain, white muscles, immature eggs, red muscles, liver. The lipid oxidation level was found to correlate with the quantity of PL, fraction content of phosphatidylethanolamine and cardiolipin, and concentration of the sum of polyunsaturated FA with the index of (20:5 divided by 22:6). It is shown that there is a regularity in the process of distribution in lipids both the sum of natural inhibitors, and individual AO, such as tocopherol, ubiquinone, ubichromenol, the quantity of which increases in accordance with the rising oxidation level of lipid substrate.

[Study of total activity of natural lipid antioxidants by chemiluminescence method]. / Izuchenie summarnoi aktivnosti prirodnykh antioksidantov lipidov khemiliuminestsentnym metodom.

The total antiradical activity of lipid antioxidants extracted from organs and tissues of fish Coregonus peled (Gmelin) was investigated using chemiluminescence method. It has been established that lipids contain antioxidants of two types. The bioantioxidants of the first type have a comparatively high efficiency constant K7eff. = (2.4-3.2) 10(6) M-1.s-1, whose value is 100 times more than that of the constant of the second type inhibitors K7eff. = (3.5-5.0) 10(4) M-1.s-1. Using the method of thin-layer chromatography such individual antioxidants of lipids as tocopherol, ubiquinon, ubichromenol were separated and quantitatively studied, as well as recorded in the presence of vitamin K, A, cholesterol. It is shown that the quantitative content of high-activity antioxidants in lipid of different kinds substantially varies (0.5-17.1) 10(-4) M; the low level of their content has been recorded for internal fat and brain lipids, the high one--for the lipids present in immature eggs, red muscles and liver.

[Chemiluminescent characteristics of ubiquinones]. / Khemiliuminestsentnye kharakteristiki ubikhinonov.

The paper deals with peculiarities of antioxidative activity of natural antioxidants (exemplified by ubiquinones) which permit their participation in the control of peroxidation intensity of membrane lipids. Ability of different ubiquinone forms to react with peroxide radicals is evaluated by chemiluminescent method. It has been shown that only reduced forms with free hydroxyl groups are highly effective.

[Role of lipid antioxidizing activity in ensuring the viability of microbial cells in air]. / Rol' antiokislitel'noi aktivnosti lipidov v obespechenii zhiznesposobnosti mikrobnykh kletok v vozdukhe.

The study made on various Escherichia coli strains used as experimental models has demonstrated that bacterial lipids possess pronounced antioxidizing activity playing an essential role in the viability of bacterial cells in the air. The content of natural antioxidants in E. coli lipids and their antiradical activity have been determined.

[Effect of lateral wick chain of tocopherols on oxidative reactions in lipids]. / O vliianii bokovoi fitil'noi tsepi tokoferolov na okislitel'nye reaktsii, protekaiushchie v lipidakh.

An injection of a alpha-tocopherol and analog devoid of the lateral chain (C1) at a dose of 90 mg/kg of body weight to experimental animals increases the levels of natural antioxidants and lipid oxidation in mouse liver 4- and 4.5-fold, respectively. The effects of alpha-tocopherol on the lipids possessing a high antiradical activity and containing the lateral chain and that of its analog, C1, also possessing a high antiradical activity but devoid of the lateral chain, were compared. The similarity of alpha-tocopherol and its analog effects on the lipids can be due to their antiradical properties. The degree of this effect is, however, different, which can be accounted for by possible fixation of the molecular in the membrane due to the presence of the lateral chain and a resulting increase of antioxidant concentration in the lipids.

[Interrelationship between the level of natural antioxidants and lipid oxidation in the normal mouse liver and after injection of alpha-tocopherol]. / Vzaimosviaz' mezhdu kolichestvom prirodnykh antioksidantov i okisliaemost'iu lipidov pecheni myshei v norme i pri vvedenii al'fa-tokoferola.

The changes in the level of natural antioxidants and lipid oxidation in normal mouse liver and after injection of the natural antioxidant alpha-tocopherol were studied. The level of natural antioxidants and lipid oxidation were increased 1--2-fold within 24 hrs; after alpha-tocopherol injection these parameters were increased 37- and 39-fold, respectively. A direct correlation between the amount of natural antioxidants and lipid oxidation in normal mouse liver and after alpha-tocopherol injection was established.

[Kinetic characteristics of the action of tocopherols as antioxidants]. / Kineticheskie osobennosti deistviia tokoferolov kak antioksidantov.

Ability of tocoferols to react with free radicals (constant K7) is determined by means of chemoluminescent method. A succession of activities is obtained for tocoferol homologues; this succession coincides with that of their biological activity. The products of oxidative transformations of tocoferols are shown to posess an inhibiting activity. Formation of sufficiently active free radicals is a characteristic feature of the antioxidative action of tocoferols. The extremal dependence of the antioxidative activity of tocoferols on their concentration is explained by the participation of these radicals in the reactions of the continuation of the oxidation chain. According to their kinetic characteristics tocoferols fall into the category of weak antioxidants. Peculiarities of the antioxidative effect of tocoferols help to explain their high biological activity. Since tocoferols have high enough values of the constants K7, even slight changes in their concentration in lipids will essentially affect the rate of oxidative processes. This peculiarity makes them rather unique, since they are first spent in the oxidation reactions proceeding in lipids, and they can be substituted only by the substances which have the constants K7 of the same order. The specificity of antioxidative properties of tocoferols enables their efficient control over peroxide oxidation of lipids.