Management of oxidative stress in the CNS: the many roles of glutathione.

An outline is given of mechanisms that generate oxidative stress and inflammation. Considered are the metabolic mechanisms that give rise to peroxides, the source of strong oxidants; the production of dicarbonyls that interact with macromolecules to form advanced glycation endproducts; and the role that activation of the transcription factor NF(Kappa)B has in the expression of pro-inflammatory genes. Management of oxidative stress is considered by outlining the central role of reduced glutathione (GSH) in peroxide scavenging, dicarbonyl scavenging and activation of NF(Kappa)B. Cellular GSH levels are dictated by the balance between consumption, oxidation of GSH, reduction of oxidized-glutathione, and synthesis. The rate-limiting enzyme in GSH synthesis is L-gamma-glutamyl-L-cysteine synthase, a phase II enzyme. Phase II enzyme inducers are found in many fruits and vegetables. It is suggested that dietary phase II enzyme inducers be investigated for their potential for preventing or retarding the development of degenerative diseases that have an underlying oxidative stress and inflammatory component.