The mechanism of action of antioxidants against lipoprotein peroxidation, evaluation based on kinetic experiments.
Peroxidation of blood lipoproteins is regarded as a key event in the development of atherosclerosis. Hence, attenuation of the oxidative modification of lipoproteins by natural and synthetic antioxidants in vivo is considered a possible way of prevention of cardiovascular disorders. The assessment of the susceptibility of lipoproteins to oxidation is commonly based on in vitro oxidation experiments. Monitoring of oxidation provides the kinetic profile characteristic for the given lipoprotein preparation. The kinetic profile of peroxidation is characterized by three major parameters: the lag preceding rapid oxidation, the maximal rate of oxidation (V(max)) and the maximal accumulation of oxidation products (OD(max)). Addition of antioxidants alters this pattern, affecting the kinetic parameters of oxidation. In particular, antioxidants may prolong the lag and/or decrease the V(max) and/or decrease the OD(max). Such specific variation of the set of kinetic parameters may provide important information on the mechanism of the inhibitory action of a given antioxidant (scavenging free radicals, metal-binding or other mechanisms). Numerous natural and synthetic compounds were reported to inhibit oxidation of lipoproteins. Based on the analysis of reported effects and theoretical considerations, we propose a simple protocol that relates the kinetic effects of a given antioxidant to the mechanism of its action.
Pinchuk
Ilya
I
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, PO Box 39040, 69978, Tel Aviv, Israel.
Lichtenberg
Dov
D
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003300:Copper / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects*; D008074:Lipoproteins / Q000097:blood*; D018384:Oxidative Stress / Q000187:drug effects
D000975:Antioxidants; D016166:Free Radical Scavengers; D008074:Lipoproteins; D003300:Copper