Anionic Tocopherol Esters as Antioxidants and Cytoprotecants

Abstract

In light of the enormous cost of health care in the United States and the considerable role of oxidative stress in causing and exacerbating human disease, it is clear that therapeutic strategies to combat oxidative injury are required. To develop pharmaceuticals that protect us from the adverse effects of oxidative stress, the critical cellular and molecular processes that (1) are responsible for acute and chronic oxidative damage and disease and (2) are responsible for protection against such damage, must be defined. By augmenting the intracellular content of an “essential” protective component at the appropriate concentration, time, and subcellular site, it may be possible to diminish or eliminate oxidative stress-mediated injury and disease. This chapter reviews the scientific evidence suggesting that anionic tocopherol esters provide mammalian cells with a form of d-α-tocopherol that enhances the effectiveness of this important endogenous antioxidant. Postulated mechanisms to explain anionic tocopherol-mediated cytoprotection will also be examined. The anionic tocopherol esters considered in this chapter include d-a-tocopheryl hemisuccinate (TS), and dl-α-tocopheryl phosphate (TP). The structures of these compounds are illustrated in Fig. 1.