Antioxidant Activity of 5,6,7,8-Tetrahydrobiopterin (BPH4) and Its Effect on Brain Damages

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The in vitro antioxidative activity of 5,6,7,8-tetrahydrobiopterin (BPH4) and its possible efficacy to brain damages were examined.BPH4 showed an extremely strong superoxide anion radical-scavenging activity in both xanthine/xanthine oxidase and rat macrophage/phorbol myristate acetate radical-generating systems. The antioxidative activity of BPH4 against both superoxide anion and hydroxyl radicals were confirmed by spin trapping-ESR spectrometry. BPH4 also protected rat brain homogenate against autooxidation.The paraquat-induced elevation of the release of lactate dehydrogenase (LDH) in cultured rat hepatocytes was suppressed by BPH4 in a dose-dependent manner. Besides, BPH4 suppressed the cell damages caused by MPTP.The effect of BPH4 on ischemic neuronal damage was examined. Cerebral ischemia was produced in the Fischer 344 rat by bilateral common carotid arteries occlusion for 60 min, which resulted in delayd neuronal death in the CA1 region of the hippocampus. Pretreatment with BPH4 reduced hippocampal neuronal damage.Finally, the effect of BPH4 on DOPA-induced cytotoxicity was examined in PC-12 cells.The toxicity of DOPA was essentially abolished by SOD and BPH4, and ameliorated by catalase, suggesting that BPH4 protects PC-12 cells from damage induced by DOPA and may inhibit the degeneration of dopamine neurons through its antioxidative activity.It is concluded that BPH4 may also have therapeutic potentials against various other diseases such as Parkinson's disease, where active oxygen radicals are involved in the pathogenesis.