Selenium Species: Uptake, Transformation and Toxicities in Differing Substrates and Their Pharmaceutical Applications

,I, Introduction A. Characteristics of Se Selenium is a member of the oxygen group of elements; it is primarily anionic but may form cations in non-aqueous solvents. Its normal oxidation states are selenate, the 6+ form (Se (VI); selenite, the 4+ (Se (IV); the very transient 2+ form, and the selenide 2 form, to which it is easily reduced. Pulse radiolysis studies (e.g., Kl&ning and Sehested, 1986) reveal the presence of Se (V) forms in aqueous selenate/selenites, reflecting the rapid reduction or oxidation of the two higher forms. The structures of Se clusters have been investigated by Hohl, et aL, (1987). Selenium is an essential micronutrient; its biochemical functions have been reviewed briefly by Wendel (1992), and by Burk (1991) and Nve (1991) amongst others. It reduces the toxicities of Hg, Pb, Cd, Cu, Ni, and As (Cuvinaralar and Furness, 1991; Parizek, 1990; Paulsson and Lundbergh, 1991; Taketani, et aL, 1991; Ingersoll, et aL, 1990; HSgberg and Alexander, 1986) and the nephrotoxicity of cisplatin (Baldew, et al., 1991). By contrast, Se deficiency enhances the nephrotoxicity of cephaloridine, a betalactam antibiotic (Kays, et aL, 1991). It is strongly nucleophilic in biological systems and usually more reactive in biological molecules than its sulfur analogues (see, for example, Nosz&l, et aL, 1991).