| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
Free radicals such as superoxide, hydroyl radical, and peroxy radical have been implicated in a wide variety of diseases such as cancer. Radiation-induced damages of protein, DNA, lipid, and tissue are also a direct result of free radical-mediated toxicity. In this study, the explorative study on scavenging the free radicals was investigated. The scavenging abilities were estimated with ESR spin-trapping method using DMPO, and for peroxyradical, decay of cumylperoxyradical was directry measured with ESR The antioxidants used in this study were the cathechin derivative, thiol containing compounds, nitroxides, and vitamin derivatives. The evaluation of the radical scavenging mechanism for nitroxides was done and the development of new chatechin derivatives as an antioxidant was studied based on the information for radical scavenging mechanism for natural phenol compounds previously explored. The scavenging reaction of free radical such as cumylperoxyl radical by nitroxides was significan
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tly accelerated by the presence of scandium ion, indicating that the reaction proceeded via an electron transfer rather than via a radical coupling reaction. Novel catechin derivatives, in which the catechol and chroman structure in (+)-catechin were constrained to be planar, was also synthesized based on previous mechanistic information about the radical-scavenging reactions by phenolic antioxidant. The radical-scavenging activity of the planar catechin derivatives thus obtained was found to be 5-10 times higher than that of (+)-catechin. Radioprotective effect of TMG (2-(α-D-glucopyranosyDmethyl-2,5,7,8-tetramethy-chroman-6-ol, a water-soluble vitamin E derivative) was studied in mice following whole-body X-ray irradiation. TMG shows excellent antioxidant activity with strong superoxide and hydroxyl radical scavenging ability. A solution of TMG (dissolved in saline) was administered intraperitoneally to C3H mice (male, 10 weeks old) before or after whole-body X-ray irradiation, and the protection for TMG against lethal irradiation was evaluated from 30-day mouse survival rate. TMG (650 mg/Kg ) was injected ip just before or after the X-ray irradiation(7 Gy), the survival rate was about 80% showing a significantly high survival rate compared to the control experiment (25%). The survival rate was 50% even when administrated 60 min after irradiation. yielding a DRF for TMG (650 mg/kg bw) was about 1.18. The radioprotective effect of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) was also investigated. When injected 30 min before the X-ray irradiation, it had the greatest radioprotective effect (DRF for edaravone (450 mg/kg bw) is about 1.3), whereas an injection after the irradiation showed no protective effect. In vivo radioprotective activity of Zn-, Mn-, Cu-, or Se-containing heat-treated Saccharomyces serevisiae yeast (Zn-yeast, Mn-yeast, Cu-yeast, Se-yeast, respectively) was examined. The 30-day survival of mice without injection of mineral-yeast was about 7%. The survival of mice to which mineral-yeast was injected at 30 min before irradiation was 65-90%, while it was more than 90% when Zn-or Cu-yeast was injected immediately after the irradiation. The Zn-yeast showed radioprotection (>80%) when injected at 60 min post-irradiation. The DRF of Zn-yeast (100 mg/kg, i. p. immediately after irradiation) was about 1.2. Less
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