Experimental antioxidant biotherapy for protection of the vascular wall by modified forms of superoxide dismutase and catalase.
The antithrombotic activities of superoxide dismutase and catalase are determined by their effects on reactive oxygen species. Modification of these enzymes with chondroitin sulphate enhances the effect due to accumulation of the derivatives on the surface of the vascular wall cells. We have shown that the effects of covalently modified biocatalysts exceed those of native enzymes, free chondroitin sulphate and their mixtures. The superoxide dismutase-chondroitin sulphate conjugate markedly reduced the thrombus mass, while the catalase-chondroitin sulphate conjugate predominantly preserved blood flow. The magnitude and duration of the antithrombotic activity of modified enzymes in a rat arterial thrombosis model allows one to expect a considerable protective effect after their combined application. A single-bolus intravenous injection of the combination between superoxide dismutase-chondroitin sulphate and catalase-chondroitin sulphate covalent conjugates had a significantly lower antithrombotic effect compared with that of the superoxide dismutase-chondroitin sulphate-catalase bienzymic covalent conjugate. This could be explained by different surface distribution of the conjugates in the circulation after their intravenous administration. Biomedical study of this approach promises a new therapeutic strategy of simple and effective protection of the vascular wall against various injuries with the use of the covalent conjugate superoxide dismutase-chondroitin sulphate-catalase. The review analyses the trends of combined application of enzyme preparations to enhance the effect of antioxidant therapy and to develop conjunctive courses of thrombolytic treatment.
Institute of Experimental Cardiology, Russian Cardiology Research Centre, 3rd Cherepkovskaya str., Moscow 121552, Russia. alexmak@cardio.ru
Alexander V
AV
Maksimenko
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001808:Blood Vessels / Q000187:drug effects* / Q000502:physiology; D002374:Catalase / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002809:Chondroitin Sulfates / Q000737:chemistry; D006801:Humans; D013482:Superoxide Dismutase / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D013678:Technology, Pharmaceutical / Q000379:methods / Q000639:trends
D000975:Antioxidants; D002809:Chondroitin Sulfates; D002374:Catalase; D013482:Superoxide Dismutase