We examined the inhibitory effect of tetrahydrobiopterin (BPH 4 ) on L-~-( 3,4-dihydroxyphenyl ) alanine (DOPA)-induced cytotoxicity in PC-12 cells. First in vitro inhibitory efficacy of BPH4 on lipid peroxidation induced by Fe 3 +-DOPA complex was confirmed by using PC-liposomes . Fe 3 +-DOPA complex at 50 /..1M caused drastic lipid peroxidation, which was significantly inhibited by BPH 4 in a dose-dependent manner. Next, we confirmed the ill vitro potency of BPH4 in cultured PC-12 cells .

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... +-DOPA complex exerted time-and dose-dependent cytotoxicity, which was also dose-dependently inhibited by BPH. possessed almost the same potenc\' as dderoxamine and a-tocopherol. We also examined the cytotoxicity of DOPA itself. A higher dose of DOPA (250/..1]\,1 ) was necessary to afford the same cytotoxic potency towards PC-12 cells as that of Fe 3 +-DOPA complex (50/..11\1). The toxicity was essentially abolished by SOD and Bl>B" and ameliorated by catalase . However, deferoxamine did not modifY the toxicity. In conclusion, BPH 4 protects both PC-liposomes and PC-12 cells from damage induced by DOPA with and without ferric ion , and may inhibit the degeneration of dopamine neurons through its antioxidatiye activity.