| Project/Area Number |
07672426
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
医薬分子機能学
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| Research Institution | Science University of Tokyo |
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Principal Investigator |
KOJIMA Shuji Science Univ.of Tokyo, Research Institute for Biological Sciences, Assistant Professor, 生命科学研究所, 講師 (90119579)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | Tetrahydrobipoterin / Antioxidant / Cytotoxicity / NO / Parkinson's disease / Dopamine / 還元型ビオプリテン / パラコート / 肝細胞傷害 / 神経毒 / PC12細胞傷害 / パーキンソン氏病 |
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| Research Abstract |
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.
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