Protective effect of tamoxifen on 1-methyl-4-phenylpyridine-induced hydroxyl radical generation in the rat striatum.
We examined whether tamoxifen could suppress 1-methyl-4-phenylpyridine (MPP(+))-induced hydroxyl radical generation in the extracellular fluid of rat striatum, using in vivo microdialysis system. MPP(+) (5 mM) enhanced generation of hydroxyl radicals with concomitant increased efflux of dopamine. Tamoxifen (1--100 microM) dose-dependently suppressed the hydroxyl radical formation induced by MPP(+). Tamoxifen (100 microM) significantly attenuated dopamine efflux induced by MPP(+). The result in the present study is the first demonstration showing the protective effect of tamoxifen on hydroxyl radical generation induced by MPP(+) by suppressing dopamine efflux.
Obata
T
T
Department of Pharmacology, Oita Medical University, 1-1, Hasama-machi, Oita 879-5593, Japan.
Kubota
S
S
D015655:1-Methyl-4-phenylpyridinium / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D020734:Parkinsonian Disorders / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology*
D018696:Neuroprotective Agents; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D017665:Hydroxyl Radical; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine