Tamoxifen protect against hydroxyl radical generation induced by phenelzine in rat striatum.
The present study was examined whether tamoxifen, a synthetic nonsteroidal antiestrogen, could suppress antidepressant drug phenelzine can increase an active dopaminergic neurotoxin, 1-methyl-4-phenylpyridinium ion (MPP(+))-induced hydroxyl radical (OH) generation in the extracellular fluid of rat striatum, using in vivo microdialysis system. Rats were anesthetized, and sodium salicylate (0.5 nmol/microl/min) was infused through a microdialysis probe to detect the generation of OH as reflected by the non-enzymatic formation of 2,3-dihydroxybenzoic acid (DHBA) in the striatum. Infusion of phenelzine (100 microM or 0.1 nmol/microl/min) into the striatum drastically increased dopamine (DA) efflux and the OH formation, trapped as 2,3-DHBA by the possible increased production of MPP(+). However, tamoxifen (100 microM) significantly suppressed phenelzine enhanced DA efflux and OH formation by MPP(+). These results in the present study is the first demonstration showing the protective effect of tamoxifen on OH generation induced by phenelzine enhanced MPP(+) by suppressing DA efflux.
Obata
Toshio
T
Department of Analytical Chemistry, Ohu University, School of Pharmaceutical Sciences, Koriyama, Fukushima 963-8611, Japan. t-obata@pha.ohu-u.ac.jp
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000633:toxicity; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D004298:Dopamine / Q000378:metabolism; D004965:Estrogen Antagonists / Q000494:pharmacology; D006540:Herbicides / Q000633:toxicity; D017665:Hydroxyl Radical / Q000378:metabolism*; D008297:Male; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism; D010624:Phenelzine / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013629:Tamoxifen / Q000494:pharmacology*
D000928:Antidepressive Agents; D004965:Estrogen Antagonists; D006540:Herbicides; D013629:Tamoxifen; D017665:Hydroxyl Radical; D006631:Amine Oxidase (Copper-Containing); D010624:Phenelzine; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine