[The effect of carnosine and carcinine on platelet function].
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Biomedical subjects
Publications and source records attributed to R P Evstigneeva.
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Data concerning lipid peroxidation and mechanism of the vitamin E inhibiting action are reviewed. Steps of initiated lipid autooxidation, formation of primary and secondary oxidation products, destabilizing the membrane structure and possessing cytotoxic effects are described. The mechanism of the antioxidant action of alpha-tocopherol, dependence of its activity on the structure and composition of the products of cooxidation of lipids and alpha-tocopherol in biological and model systems are also discussed.
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Acetylenic fatty acids, 8,11,14-eicosatrienoic, 5,8,11,14-eicosatetraenoic and 5,8,11,14,17-eicosapentaenoic acids, were compared with respect to their effects on the particulate prostaglandin H synthase. All the acetylenic acids inactivated the enzyme in a time-dependent manner. The eicosatriynoic and eicosatetraynoic acids exhibited comparable efficacies, whereas the eicosapentaenoic acid proved to be a weaker inactivator. The time-courses of inactivation fitted a kinetic model suggest an enzyme-catalysed conversion of the compounds via alternative suicidal and non-suicidal routes. The characteristics of inactivation of prostaglandin H synthase differ from those of lipoxygenases.
Fluorescence spectra of alpha-tocopherol and its mixtures with oxygenated derivatives of fatty acids--linoleic acid hydroperoxide, hydroxylinoleic and ricinoleic acids--were investigated in terms of the excitation and emission dependence on the concentration of components in acetonitrile solution. In accordance with our results, formation of the alpha-tocopherol excimer and exciplex with the oxygen-containing derivatives of polyunsaturated fatty acids was suggested. The character of the interaction between components of the excited complexes and their possible role in peroxidation of lipids are discussed.
Interaction of alpha-tocopherol with phospholipids, oleic, ricinoleic acids and linoleic acid hydroperoxides was investigated by means of 31P NMR spectroscopy on a model artificial membranes containing egg phosphatidylcholine and lysophosphatidylcholine. alpha-Tocopherol was shown to support the bilayer organization of lysophospholipids, whereas its introduction into the lecithin-water system stimulated the hexagonal phase formation. Free fatty acids exhibited a synergism to alpha-tocopherol, the effect of the hexagonal phase formation being at most increased by oxygenated acids--ricinoleic acid and linoleic acid hydroperoxides. In accordance with the experimental data, a conclusion about modifying and structuring action of alpha-tocopherol was made. Origin of the alpha-tocopherol's modulating effect on the membrane structure and a possible role of hexagonal phase forming upon its action in the course of peroxidation of lipids was discussed.
Formation of a complex between alpha-tocopherol or its analogues in the excited state and fatty acids or their hydroperoxides has been suggested basing on the fluorescence quenching experimental data. The possible mechanism of the complex formation, its nature and role in the fatty acid peroxidation is discussed.
Spirodimers, dimers, quinones of alpha-tocopherol and chroman C1 have been synthesized by the alpha-tocopherol and chroman Ci oxidation with K3[Fe(CN)6] and FeCl3. Products of the oxidative transformation of alpha-tocopherol and chroman Ci, viz. dimers, quinones and trimers, in the media of ethyllinoleate and nonane have been identified by HPLC, TLC, UV, IR and 1H NMR spectroscopy. The mechanism of the transformation and modifying activity of chromans under various oxidation conditions are discussed with regards to the experimental data.
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Hepatitis delta virus (HDV), a recently discovered infectious agent, participates in severe, often lethal forms of acute and chronic hepatitis and liver cirrhosis. Based on theoretical analysis of secondary structure, hydrophilicity and acrophilicity data, several regions of HDV antigen, presumably containing B-epitopes, have been revealed and the corresponding peptides have been synthesized by the solid phase method. All the peptides obtained reacted with the respective antipeptide rabbit sera. The peptides and their conjugates with BSA or KLH were used for ELISA with individual and pooled anti-HD-positive sera from patients with chronic delta hepatitis. The high antigenicity of the peptide 65-80 shows that one of the antigenically active regions of HDAg is situated between these amino acid residues and that the peptide may be used for detection of anti-HD antibodies in patients blood sera.
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We synthesized the 24-41, 30-36, 31-36, 24-30 fragments of the preS1-region of the hepatitis B (subtype ayw) envelope. The peptides were prepared by the solid phase synthesis on perfluorpolyethylene polymer grafted with polystyrene. The peptide chains were elongated from C-terminus using activated esters and symmetrical anhydrides of Boc-amino acids, cleaved off the solid phase by HBr or TFMSA in TFA, purified by gel filtration, and, after conjugation with protein carriers, inoculated into test animals. The resultant antibodies were shown to react with peptides. The blood sera from patients with acute hepatitis B reacted with the conjugates of peptides 24-41, 30-36, 31-36 in the immunoenzymic solid phase assay. The monoclonal antibodies for the preS1-polypeptide were shown to react with peptides 24-41, 30-36, 31-36 and with their conjugates. The results obtained were proved by the data of the epitope-mapping with overlapping hexapeptides.
The review deals with the basic features of the fatty acid lipoxygenation resulting in the formation of leukotrienes, hydroxy fatty acids, lipoxins, hepoxylins. The biological role, prospects for the further studies of this class of bioregulators are discussed.
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The effects of phosphocreatine and tocopheryl phosphate and their combined use in ischemia and reperfusion of the heart were studied in anesthetized dogs. The investigation focused on the size of myocardial infarction and left ventricular contractility, ischemic and reperfusion arrhythmias were assessed using Holter monitoring. Phosphocreatine was found to reduce the number of arrhythmias and to prevent the fatal outcomes in myocardial ischemia animals but not to influence the reperfusion rhythm disturbances. Combined administration of tocopheryl phosphate and phosphocreatine, in contrast to their isolated use, completely prevented the development of ventricular fibrillations and fatal outcomes in the animals with reconstructed coronary flow. Administration of phosphocreatine restricted the infarction size, combined use of the drugs facilitated its further reduction, while the group with isolated administration of tocopheryl phosphate showed the infarction size to differ insignificantly from the control values. Combined administration of the drugs, unlike their use alone, improved left ventricular contractility in reperfusion of ischemic myocardium. The cardioprotective effect observed in combined administration of the drugs was attended with depressed lipid peroxidation in reperfused myocardium.