Session Speaker

Enzymatic Antioxidants: Next Phase Of Pharmacological Effort To Fight Oxidative Stress?
Alexander Vasilievich Maksimenko, Vavaev A.V., Tischenko E.G.

The focus in the research of antioxidants is notably displaced in favour of research of enzyme derivatives at present. Extracellular superoxide dismutase (EC-SOD) is of the particular interest, as it demonstrates in vivo the protective action against development of atherosclerosis, hypertension, heart failure, and diabetes mellitus. The reliable association of coronary artery disease with the decreased level of heparin-released EC-SOD was established in clinical researches. To base and develop antioxidant therapy, various SOD isozymes, catalase (CAT), the methods of experimental gene therapy, combined use of SOD- and CAT-activities are used.

We prepared by ?ovalent binding the Cu,Zn-SOD to CAT via the vascular wall glycosaminoglycan chondroitin sulfate (CHS) the bienzyme conjugate (SOD-CHS-CAT) which manifests in vivo the highest antithrombotic activity. The bienzyme conjugate was effective at doses two orders of magnitude smaller than those for native SOD and CAT and an order of magnitude smaller than that for CHS-modified derivatives, administered either individually or as a mixture. Our results demonstrate the importance of the attachment of a bioantioxidant to the vascular wall and the connection of superoxide dismutase and catalase activities on its surface. Pre-clinical research data approve the reliable option to gain for it the status of drug candidate.