gamma-Tocopherol traps mutagenic electrophiles such as NOx and complements alpha-tocopherol: Physiological implications

Peroxynitrite, a powerful mutagenic oxidant and nitrating species, is formed by the near diffusion-limited reaction of . NO and O-2(.-) during activation of phagocytes. Chronic inflammation induced by phagocytes Is a major contributor to cancer and other degenerative diseases, We examined how gamma-tocopherol (gamma T), the principal form of vitamin E in the United States diet, and alpha-tocopherol (alpha T), the major form in supplements, protect against peroxynitrite-induced lipid oxidation, Lipid hydroperoxide formation in liposomes (but not isolated low-density lipoprotein) exposed to peroxynitrite or the . NO and O-2(.-) generator SIN-1 (3-morpholinosydnonimine) was inhibited more effectively by gamma T than alpha T. More importantly, nitration of gamma T at the nucleophilic 5-position, which proceeded in both liposomes and human low density lipoprotein at yields of approximate to 50% and approximate to 75%, respectively, was not affected by the presence of alpha T, These results suggest that despite alpha T's action as an antioxidant gamma T is required to effectively remove the peroxynitrite-derived nitrating species, We postulate that gamma T acts in vivo as a trap for membrane-soluble electrophilic nitrogen oxides and other electrophilic mutagens, forming stable carbon-centered adducts through the nucleophilic 5-position, which is blocked in alpha T, Because large doses of dietary alpha T displace gamma T in plasma and other tissues, the current wisdom of vitamin E supplementation with primarily alpha T should be reconsidered.