[Antioxidant and antiaggregant effects of covalent bienzyme superoxide dismutase-chondroitin sulfate-catalase conjugate in platelet interactions].

A covalent bienzyme superoxide dismutase-chondroitin sulfate-catalase conjugate (SOD-CHS-CAT) demonstrated the dose-dependent inhibitory action on induced aggregation of platelets in the presence of hydrogen peroxide. Antioxidant activity of SOD-CHS-CAT appeared at much lower doses than for other CAT derivatives. We detected the antiaggregation effect of SOD-CHS-CAT for platelet aggregation induced by ADP, serotonin, TRAP (with their different mechanism of action). Novel properties of SOD-CHS-CAT confirmed with its action agains spread-eagle platelets on glass surface. The new characteristics of SOD-CHS-CAT conjugate underline the prospects of its biopharmaceutical development for antioxidant therapy.

Effect of hydrogen peroxide and catalase derivatives on functional activity of platelets.

Effects of H(2)O(2) on platelet aggregation were estimated in vitro in the presence and absence of inductors (ADP, serotonin, TRAP) and native and modified catalase. Dose-dependent effect of H(2)O(2) (50 µM or more) was investigated in a pathophysiological concentration of 300 µM inducing platelet aggregation. H(2)O(2) modulated aggregation induced by ADP, serotonin, and TRAP significantly increasing the initial platelet aggregation followed by disaggregation, which was always more pronounced than in control. Catalase derivatives (native and modified forms) dose-dependently reduced the effect of H(2)O(2) and completely abolished it in a dose of 9000 U catalase activity per 1 ml of solution for native catalase and 1200 U/ml for modified one. Modified catalase, in contrast to native one, produced an independent inhibitory effect on induced platelet aggregation. Components of modified catalase (individual substance and simple mixture) had no antiaggregant effect.

[Do electrostatic interactions determine glycation of hyaluronidase derivatives with N-acethylhexosamines?].

Glycation of native hyaluronidase and its chondroitin sulfate modified form was studied with N-acethylglucosamine, N-acethylgalactosamine and their mixture, as well as hyaluronan fragments (n = 0-4) and their mixture. The modified form of hyaluronidase exhibited higher inactivation than native enzyme. The chondroitin sulfate modification of hyaluronidase altered its surface electrostatic potential, but this effect was not crucial for inactivation of hyaluronidase derivatives. The observed picture of the glycation action on hyaluronidase derivatives was opposite for glycation with mono- and di-saccharides. Such results give us the informative enzyme test for in vivo system in order to determine the dominant type of glycation agents in bloodstream and its origin.

[Antithrombotic effect of catalase and chondroitin sulfate derivatives in arterial damage in rats]. / Antitromboticheskoe deistvie proizvodnykh katalazy i khondroitinsul' fata pri arterial'nom porazhenii u krys.

The antithrombotic action of catalase and chondroitin sulfate derivatives was studied on the rat arterial thrombosis induced by treatment of vessel with ferrous chloride solution. The effect of native or chondroitin sulfate modified catalase, as well as the mixture of native catalase and free chondroitin sulfate in ratio which is equal to their content in conjugate was compared in respect to corresponding doses according to active catalase content. The antithrombotic action of conjugate and its component mixture is rather similar with each other and significantly exceeds the effect of native enzyme. The conjugate was the most effective in respect to retarding/prevention of arterial occlusion. The action of catalase preparations was altered the thrombus structure conducting blood stream retention at the low doses used. The directions of further studies of antithrombotic activity for catalase, superoxide dismutase and chondroitin sulfate derivatives were founded.

[Antithrombotic activity of complexes of superoxide dismutase with chondroitin sulfate in arterial damage in rats]. / Antitromboticheskaia aktivnost' kompleksov superoksidismutazy s khondroitinsul'fatom pri arterial'nom porazhenii u krys.

The comparative antithrombotic activity of superoxide dismutase and chondroitin sulfate in the form of covalent or noncovalent complexes was studied on the rat arterial thrombosis induced by treatment of vessel with ferrous chloride solution. The covalent conjugate between superoxide dismutase and chondroitin sulfate has been shown to exert the highest antithrombotic effect. The higher antithrombotic activity of covalent conjugate is stipulated by its coupling on the glycocalyx of vascular wall and by the stability of the covalent bond between superoxide dismutase subunits and chondroitin sulfate.

[Alimentary modification of catecholamine levels and status of the thiol-dependent protective system in the brain in convulsive syndrome]. / Alimentarnaia modifikatsiia urovnei katekholaminov i sostoianiia sistemy tiolzavisimoi zashchity v mozge v usloviiakh éksperimental'nogo sudorozhnogo sindroma.

Alimentary modification of CA metabolism and the activity of thiol-depended protective systems in corazol seizures have been studied. Chronic seizures causes the decrease in tissue CA levels. Rations enriched with regulators of inhibitory neurotransmitters metabolism significantly diminished above mentioned effect. Protective influence of rations could be attributed at least partly to the activation of thiol-depended mechanisms prevented the excess CA oxidation.

[Biochemical bases of prevention of the cytotoxic effect of xenobiotics]. / Biokhimicheskie osnovy profilaktiki tsitotoksicheskogo deistviia ksenobiotikov.

Possible sources of cytotoxicity of xenobiotics and main mechanisms of realization of their damaging effect are briefly considered. Protective system of a cell is characterized with regard for the peculiarities essential for development of principles of alimentary prophylaxis of cytotoxic effects of foreign compounds. Modern approaches to alimentary modification of the processes of biotransformation of xenobiotics and promotion of protective capacities of a cell are discussed.

[Antifibrosis effect of modified forms of catalase and superoxide dismutase in experimental silicosis]. / Antifibroznoe deistvie modifitsirovannykh form katalazy i superoksiddismutazy pri éksperimental'nom silikoze.

The forms of catalase modified by treatment with dextran aldehyde were obtained and studied. Efficacy of the preparations containing native and modified forms of catalase and superoxide dismutase as well as their covalent bienzyme conjugate containing catalase-dextran aldehyde-superoxide dismutase was studied in rats with simulated silicosis. The preparations were administered into rats by means of inhalation and intraperitoneal injection. Positive protective effect exhibited a mixture of native enzymes and their covalent conjugate. The most pronounced additional effect was caused by the mixture of native catalase and superoxide dismutase as compared with modified preparation of superoxide dismutase. The preparation of bienzyme containing conjugate was less effective.

[Antifibrotic effects of aldehyde dextran modified superoxide dismutase in experimental silicosis]. / Antifibroznoe deistvie modifitsirovannoi al'degiddekstranom superoksiddismutazy pri éksperimental'nom silikoze.

The present paper dwells on biomedical study of aldehyde dextran modified superoxide dismutase. Pharmacokinetic data demonstrated that modification of superoxide dismutase increased its half-time. A rat model of experimental silicosis showed that aldehyde dextran modified superoxide dismutase inhibited evolving fibrosis in the lungs. The same dose of native enzyme produced no therapeutic effect. Thus, superoxide dismutase can be considered as a potential agent for treatment of fibrosis due to its modification.

[Assessment of the composition and structure of covalent complexes of superoxide dismutase with aldehyde dextran by analytical ultracentrifugation]. / Otsenka sostava i stroeniia kovalentnykh kompleksov superoksiddismutazy s al'degiddekstranom metodom analiticheskogo ul'tratsentrifugirovaniia.

Superoxide dismutase was covalently coupled wih aldehyde dextran, a polymeric carrier of molecular mass of 70 kDa. Modification produced an increase in the enzyme thermostability. Modified preparations retained a high specific activity. The composition of the thus obtained conjugates was analyzed by the ultracentrifugation and diffusion methods. The protein induced the destruction of aldehyde dextran, the enzyme being modified by its fragments. The presence of aldehyde dextran excess in the incubation medium promoted superoxide dismutase dissociation into individual subunits. At the enzyme/carrier ratio of 1:02 modification occurred as covalent coupling of the biocatalyst subunits and its one-point modification.

[Drug preparations of immobilized enzymes with enhanced affinity for the site of action]. / Lekarstvennye preparaty immobilizovannykh fermentov s povyshennym srodstvom k mestu deistviia.

Several approaches to development of systems for directed transport of drugs are illustrated by an example of thrombolytic therapy. Preparation and properties of enzyme derivatives with increased tropism to the thrombus material due to modification of enzymes by fibrinogen or specific antibodies are discussed. The data on directed transport of drugs under the action of the magnetic field and on the selective action of drugs on culture cells are also presented.

[Fibrinolytic action of an enzyme preparation conjugated with specific antibodies]. / Fibrinoliticheskoe deistvie fermentnogo preparata, kon"iugirovannogo so spetsificheskimi antitelami.

The authors have modified alpha-chymotrypsin covalently bound via aldehyde dextran with polyclonal antibodies to fibrinogen. Modification does not lead to any substantial changes in the catalytic properties of the enzymes or to appreciable losses in specific activity of antibodies. At the same time in experimental thrombolysis in vitro, the derivatives obtained exhibit a higher fibrinolytic action as compared with control preparations. It is assumed that the effect observed is accounted for by an increase in tropism of the conjugate obtained to the fibrin clot.

[Qualitative and quantitative composition of protein fractions in the serum of rats based on the data of polyacrylamide gel electrophoresis]. / Kachestvennyi i kolichestvennyi sostav belkovykh fraktsii syvorotki krovi krys po dannym élektroforeza v poliakrilamidnom gele.

The protein spectrum of rat blood serum was studied by disc-electrophoresis in polyacrylamide gel. The obtained proteinograms of the blood serum contained 16-18 protein fractions which were identified for haptoglobin, ceruloplasmin, transferrin; the coefficient of mobility for albumin was also calculated for them. The rat blood serum proteinogram and the human blood serum proteinogram obtained under analogous conditions of electrophoresis are discussed for their peculiarities and similarity.