We have investigated the protective effect of (-)-epigallocatechin gallate (EGCG) on alpha-amino-3-hydroxy-5-methyl-4-isoxazolo propionate (AMPA)-induced toxicity in cultured rat hippocampal neurons. Treatment of 24 h AMPA (10 muM) reduced the neuronal viability in both survival neuron counting and MTT reduction assay compared with control, with increase in cellular concentrations of hydrogen peroxide and malondialdehyde. These responses to AMPA were significantly blocked by co-treatments with EGCG (10 muM), which effect was very similar to the protective ability of a known antioxidant catalase (2000 U/ml). AMPA (50 muM) elicited the increase in intracellular calcium concentration ([Ca2+](i)) on which EGCG significantly attenuated both peak amplitude and sustained nature of that [Ca2+](i) increase in a dose-dependent manner. These data suggest that EGCG has a neuroprotective effect against AMPA through inhibition of AMPA-induced [Ca2+](i) increase and consequent attenuation of reactive oxygen species production and lipid peroxidation as an antioxidant and a radical scavenger. (C) 2002 Elsevier Science (USA).