Protection against oxidative damage and cell death by the natural antioxidant ergothioneine

The natural antioxidant ergothioneine (EGT) was tested for its ability to i nhibit cell death caused by hydrogen peroxide (H2O2) and to inhibit DNA oxi dation by peroxynitrite (ONOO-) in human neuronal hybridoma cell line (N-18 -RE-105). High concentrations of EGT (5 mM) were tolerated by the N-18-RE-1 05 cells. N-acetylcysteine (NAC) was not well tolerated by the cells at con centrations greater than 3 mM (cell viability averaged 50%). increasing con centrations of EGT increases cell viability in the presence of NAG. EGT at concentrations up to 2 mM weakly improved cell viability in the presence of H2O2. NAC at concentrations up to 2 mM weakly decreased, but not significa ntly, the viability of the cells. At a higher concentration of 5 man, NAC w eakly protected the neuronal cells against the H2O2-induced cell death. The protection was significantly enhanced by preincubation with EGT. Ergothion eine inhibited ONOO--induced oxidative damage in isolated calf thymus DNA a nd DNA in N-18-RE-105 cells. The concentration of EGT in human and mammalia n tissue has been estimated to be 1-2 mM, which suggests that EGT may serve as a non-toxic thiol buffering antioxidant in vivo and may find applicatio ns in pharmaceutical preparations where oxidative stability is desired. (C) 1999 Elsevier Science Ltd All rights reserved.