The antioxidant nutrients and disease prevention--what do we know and what do we need to find out?

Abstract

The symposium started with several lectures that outlined and explained the mechanistic background necessary to understand free radical reactions, and especially those reactions that are important in free radical biology. These lectures stressed the widespread nature of radical-mediated oxidative processes in normal biochemistry as well as in pathology and also the role ofantioxidant nutrients in protecting biological systems against oxidative stress. Some speakers addressed the difficulty in proving that a given biological effect results from free radical-mediated processes. Free radicals are so reactive that they cannot be directly observed in biological systems. Thus, we are on the trail ofan elusive species, and we must look for its “footprints.” Although a number of footprints that mark free radical activity in biological samples have been reported (1, 2), there is a need both to validate those that we have and to develop newer methods that are more sensitive and more specific. The task of proving radical involvement in chronic disease conditions is often difficult. For example, smokers do not have a reduced level of vitamin E in blood plasma, but they do have a strikingly lower level of vitamin E in their pulmonary lavage fluid (3). Also, smokers have blood plasma that gives very nearly normal values ofthiobarbaturic acid reactive materials (TBARS), but smokers exhale elevated amounts ofethane and pentane (4). Thus, cigarette smoke puts the greatest oxidative burden on the lung, as seems reasonable. Therefore, methods for detecting radical involvement must be targeted to, and sensitive to, oxidative damage to the lung when probing oxidative stress in smokers. Several speakers provided insights into the rates at which vitamins E and C are oxidized in model systems, ranging from simple phospholipids to human blood serum and the LDL partide. More studies are needed of the mechanisms by which antioxidant nutrients protect model systems against oxidation. For example, Professor Niki presented data on the oxidation of human blood serum, showing that vitamin E in the LDL particle disappears very much faster than does vitamin E in the red blood cell membrane. While reasons for this can be hypothesized, it is an interesting observation that is worthy of further work. Professor Esterbauer presented studies of the oxidation of the LDL particle, a process that may be involved in the development offatty streaks in atherosclerosis. Esterbauer’s group has shown, for example, that oxidation of polyunsaturated fatty acids (PUFAs) leads to the production ofa number ofaldehydes, most notably malonaldehyde and 4-hydroxy-2-nonenal (HNE) (5). These aldehydes can diffuse farther in the cell than can reactive radicals, and HNE therefore may be implicated in damage to LDL.