| Project/Area Number |
07672335
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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 |
Physical pharmacy
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
FUJII Hirotada Tokyo Metropolitan Institute of Medical Science, Department of Inflammation, Researcher, 炎症研究部門, 研究員 (70209013)
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| Co-Investigator(Kenkyū-buntansha) |
MIKI Toshiaki Tokyo Metropolitan Institute of Medical Science, Department of physiological che, 医化学研究部門, 研究員 (10239204)
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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 |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | free radicals / non-invasive analysis / L-band ESR / aging / spin trapping / NO |
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| Research Abstract |
Although the existence of free radicals in drug metabolites can be inferred from end product analysis in our modern environment, no study on the effects of these xenobiotic free radicals on aging has been carried out.In this project, we have studied the effects of xenobiotic free radicals generated from several drugs on aging of mice using low-frequency in vivo electron spin resonance (ESR) spectroscopy.
(1) We have employed the ESR spin trapping technique in vivo to detect the formation of the 5,5-dimethyl-1-pyrroline-N-oxide (DMPO)/hemoglobin thiyl free radical in rats following administration of either hydrazine or phenylhydrazine. Six line, strongly immobilized ESR spectra of hemoglobin thiyl radicals were observed in rats by L-band ESR spectrometer.
(2) Non-invasive detection of nitric oxide (NO) which is generated by induced NO synthase : We have carried out direct, real-time, in vivo measurement of NO in mice using the water soluble metal chelator complex, N-methyl-D-glucamine dithiocarbamate (MGD), and Fe (II) as monitored by ESR at L-band microwave frequency. The three-line ESR spectrum from the product [(MGD)_2-Fe (II)-NO] was obtained non-invasively in lipopolysaccharide (LPS)-treated mice. The spectrum was markedly suppressed by the administration, prior to LPS injection, of phenyl N-tert-butyl nitrone (PBN), an inhibitor of the expression of induced no synthase.
(3) In vivo ESR measurements of [(MGD)_2-Fe (II)-NO] at several regions in the body (from the head to the tail) indicated that the NO was generated mostly in the upper abdomen near the liver. The concentration of NO complex detected in the liver was about 100 mu M at maximum.
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