title: Protection against oxidative damage and cell death by the natural antioxidant ergothioneine.
abstract: The natural antioxidant ergothioneine (EGT) was tested for its ability to inhibit cell death caused by hydrogen peroxide (H2O2) and to inhibit DNA oxidation 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-105 cells. N-acetylcysteine (NAC) was not well tolerated by the cells at concentrations greater than 3 mM (cell viability averaged 50%). Increasing concentrations of EGT increases cell viability in the presence of NAC. 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 significantly, the viability of the cells. At a higher concentration of 5 mM, NAC weakly protected the neuronal cells against the H2O2-induced cell death. The protection was significantly enhanced by preincubation with EGT. Ergothioneine inhibited ONOO(-)-induced oxidative damage in isolated calf thymus DNA and DNA in N-18-RE-105 cells. The concentration of EGT in human and mammalian 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 applications in pharmaceutical preparations where oxidative stability is desired.
authors.affiliation: Department of Biology, Imperial College of Science, Technology and Medicine, London, UK.
authors.forename: O I
authors.initials: OI
authors.lastname: Aruoma
authors.forename: J P
authors.initials: JP
authors.lastname: Spencer
authors.forename: N
authors.initials: N
authors.lastname: Mahmood
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002417:Cattle; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D004880:Ergothioneine / Q000494:pharmacology*; D006801:Humans; D006825:Hybridomas; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000633:toxicity; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009566:Nitrates / Q000037:antagonists & inhibitors / Q000633:toxicity; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats
chemical_list: D000975:Antioxidants; D009566:Nitrates; C039642:peroxynitric acid; D004247:DNA; D006861:Hydrogen Peroxide; D004880:Ergothioneine