Antioxidant Enzymes as Potential Targets in Cardioprotection and Treatment of Cardiovascular Diseases. Enzyme Antioxidants: The Next Stage of Pharmacological Counterwork to the Oxidative Stress

Abstract

The focus in antioxidant research is on enzyme derivative investigations. Extracellular superoxide dismutase (EC-SOD) is of particular interest, as it demonstrates in vivo the protective action against development of atherosclerosis, hypertension, heart failure, diabetes mellitus. The reliable association of coronary artery disease with decreased level of heparin-released EC-SOD was established in clinical research. To create a base for and to develop antioxidant therapy, various SOD isozymes, catalase (CAT), methods of gene therapy, and combined applications of enzymes are used. Covalent bienzyme SOD-CHS-CAT conjugate (CHS, chondroitin sulphate) showed high efficacy and safety as the drug candidate. There is an evident trend to use the components of glycocalyx and extra-cellular matrix for target delivery of medical substances. Development of new enzyme antioxidants for therapeutic application is closely connected with progress in medical biotechnology, the pharmaceutical industry, and the bioeconomy.

Functional benefits of PLGA particulates carrying VEGF and CoQ10 in an animal of myocardial ischemia

“…Cardioprotection is more of a prophylactic measure to prevent or reduce myocardial damage and the use of antioxidants is gaining importance in this area (Burgoyne et al, 2012, Maksimenko andVavaev, 2012). Coenzyme Q 10 (CoQ 10 ), also known as ubiquinone, is a molecule that is responsible of the electron flow between complexes one and two with complex three in the electron transport chain (Sohal and Forster, 2007).…”

Ratio of S-adenosylmethionine to S-adenosylhomocysteine as a sensitive indicator of atherosclerosis

“…EC-SOD regulates baseline cardiac morphology and protects the heart from fibrosis, apoptosis and loss of function following oxidative injury caused by HHcy (24). As shown in Fig.…”

Translational research into vascular wall function: regulatory effects of systemic and specific factors

“…Specific features of chondroitin sulfate [58][59][60] render it into a productive linking agent for antioxidant enzymes [45] and facilitate targeting of the resulting conjugates at the glycocalyx over vascular lesions. This may account for the effectiveness of SOD-CHS-CAT conjugate at small doses [45,46]. It should be noted that in an animal model of endotoxic shock SOD-CHS-CAT significantly increases viability after preventive and therapeutic administration [56].…”

“…Formation of antioxidant therapy implies investigation and development of new antioxidant drugs [45,46]. Protective effects of ascorbic acid, trolox, melatonin, polyphenols [47], human recombinant Mn-SOD [48] in hepatic disorders, the effects of chemically modified SOD in lipid oxidation and antioxidant status in diabetic rats [49], changes in SOD and catalase (CAT) activities due to cadmium-induced incorrect folding [50] have been examined.…”

“…The antithrombotic effect in vivo produced by the conjugate is higher than those of various combinations and mixtures of its components (native or modified) [46,56], is achieved at low doses (25-50 U SOD and 55-110 U CAT per rat), which is one or two orders of magnitude lower than those for native or modified enzymes [57]. Chondroitin sulfate content on the vascular surface over atherosclerotic lesions increases at the initial stages of atherogenesis [58].…”