ANTIOXIDANT AND PROOXIDANT ACTIVITY OF ALPHA-TOCOPHEROL IN HUMAN PLASMA AND LOW-DENSITY-LIPOPROTEIN

alpha-Tocopherol is a classical lipophilic antioxidant well known as a scavenger of free radicals in a hydrophobic milieu. However, it can d evelop both anti- and prooxidant activity in isolated low density lipo protein (LDL). It is unknown how these activities are balanced in vivo in human plasma. We studied oxidation of plasma and LDL isolated from healthy donors or from a patient with familial isolated vitamin E def iciency and supplemented with alpha-tocopherol in vivo or in vitro. We found that alpha-tocopherol supplementation decreased plasma and LDL oxidizability under strong oxidative conditions when oxidation was ini tiated by high amounts of Cu2+ or 2,2'-azobis-(2-amidinopropane) hydro chloride (AAPH). Tile effect was independent of the presence of ascorb ate in the samples. Under conditions of mild oxidation by low amounts or Cu2+ or AAPH, alpha-tocopherol supplementation decreased plasma oxi dizability only in the presence of physiological amounts of ascorbate. A prooxidant effect of a-tocopherol was found under mild oxidative co nditions in highly diluted (150-fold) plasma and in isolated LDL. Thes e results indicate that the level of oxidative stress and concentratio n of co-antioxidants, such as ascorbate, capable of regenerating alpha -tocopherol in the oxidizing lipoprotein particle, appear to represent major factors determining alpha-tocopherol activity towards oxidation both in human plasma and LDL. in vivo, in the presence of high concen trations of co-antioxidants and under mild oxidative conditions, alpha -tocopherol should normally behave as an antioxidant. This antioxidant activity is also expected to prevail under strong oxidative condition s independently of the presence of co-antioxidants bur it may evolve i nto prooxidant, when tile co-antioxidants are exhausted under conditio ns of mild oxidation. It remains to be shown whether such a transforma tion is physiologically relevant and can occur in vivo.