Studies on the behavior of free radicals as a neurotoxin in the central nervous system

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Free radicals have toxic effects to the central nervous system. To assess this effects, we studied the behavior of free radicals in the living biological system using novel methods.(1)in vivo ESR studyMetabolism of a stable nitroxide radical, TEMPOL, in living rats was observed using an L-band ESR system. TEMPOL was repeatedly injected at a 5-min interval via tail vein. The metabolism was analyzed in terms of the half-lives of TEMPOL elimination from the rat. In control animals, repeated injection of TEMPOL caused gradual prolongation of the half-lives. On the ontrary for rats receiving oral idebenone (a therapeutic agent for cerebro-vascular diseases) or vitamin E for 2-4 weeks, the prolongation was not found.In addition, analysis of the half-lives of TEMPOL in rats ranging from 4 to 16 weeks-old suggests a lower ability to eliminate radicals in older rats.(2)developments of microelectrode for bioradicalsNitric oxide(NO) is a important bioreguratory molecules. And it is assumed that NO also have toxic effects in the central nervous systems. The technology, however, is not available for direct analysis of the release and/or distributions of NO.We developed a microelectrode based on polymeric metalloporphyrin and carbon fibers. Using this electrode we have detected NO occuring in the rat brain by administratrion of NMDA.