Antioxidant and prooxidant activity of α-tocopherol in human plasma and low density lipoprotein

α-Tocopherol is a classical lipophilic antioxidant well known as a scavenger of free radicals in a hydrophobic milieu. However, it can develop both anti- and prooxidant activity in isolated low density lipoprotein (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 deficiency and supplemented with α- tocopherol in vivo or in vitro. We found that α-tocopherol supplementation decreased plasma and LDL oxidizability under strong oxidative conditions when oxidation was initiated by high amounts of Cu²⁺ or 2,2'-azobis-(2- amidinopropane) hydrochloride (AAPH). The effect was independent of the presence of ascorbate in the samples. Under conditions of mild oxidation by low amounts of Cu²⁺ or AAPH, α-tocopherol supplementation decreased plasma oxidizability only in the presence of physiological amounts of ascorbate. A prooxidant effect of α-tocopherol was found trader mild oxidative conditions in highly diluted (150-fold) plasma and in isolated LDL. These results indicate that the level of oxidative stress and concentration of co- antioxidants, such as ascorbate, capable of regenerating α-tocopherol in the oxidizing lipoprotein particle, appear to represent major factors determining α-tocopherol activity towards oxidation both in human plasma and LDL. In vivo, in the presence of high concentrations of co-antioxidants and under mild oxidative conditions, α-tocopherol should normally behave as an antioxidant. This antioxidant activity is also expected to prevail under strong oxidative conditions independently of the presence of co-antioxidants but it may evolve into prooxidant, when the co-antioxidants are exhausted under conditions of mild oxidation. It remains to be shown whether such a transformation is physiologically relevant and can occur in vivo.