EVALUATING OXIDATION PROCESSES IN RELATION TO CARDIOVASCULAR-DISEASE - A CURRENT REVIEW OF OXIDANT ANTIOXIDANT METHODOLOGY/

Evidence has now been accumulated of the involvement of reactive oxyge n species (ROS)(1) in the onset of several pathological conditions, in cluding atherosclerosis (1, 2), cancer (3-5), cataract (6), postischem ic reoxygenation injury (3), rheumatoid arthritis (7), and complicatio ns associated with aging (8). However, the implication of ROS in the a bove mentioned diseases has often been hypothesized on the basis of in direct observations, ie antioxidant supplementation contributing to th e alleviation of certain diseases. Furthermore, negative results of cl inical trials have been published, dampening enthusiasm and calling fo r a more cautious approach to antioxidant therapy (2, 9, 10). Intrinsi c uncertainties in the selection of appropriate markers of ROS-mediate d processes, related to diseases, as well as in the dosage and duratio n of treatments, make it difficult to plan interventional studies and to evaluate the results.ROS, such as hydroxyl (OH.), superoxide (O-2-) , or peroxyl (RO2.) radicals, are produced in the body under physiolog ical conditions or in response to external injuries and they become to xic when their levels exceed the antioxidant capacity of the body: it should be clear to the reader that a continuous production of free rad icals and ROS is a perfectly physiological process (the human body can produce over 2 Kg of superoxide per year (11)) in addition to being a defense mechanism by which activated phagocytes destroy noxious invad ers (12). Research concerning the antioxidant(2) activity of individua l compounds, as well as of mixtures and of body fluids, should take at least three interdependent variables into account: (i) the substrate to be studied, (ii) the oxidative system(s) employed, and (iii) the pa rameters of oxidation to be evaluated. Individual substrates generate different products when exposed to different oxidative conditions ((12 ), Bellomo, unpublished data): the widest array of tests should thus b e employed in antioxidant investigation. In addition, different ROS-ge nerated markers may be differentially correlated with pathogenic proce sses. This review is an update of the approaches and methods used in t he evaluation of ROS-mediated processes and it also attempts to outlin e some thought-provoking topics concerning the study of antioxidants a s related to human pathology.