The effect of tamoxifen on opening ATP-sensitive K+ channels enhances hydroxyl radical generation in rat striatum

Autor: Toshio Obata
Rok vydání: 2019
Předmět:
Zdroj: Journal of Clinical Neuroscience. 63:196-201
ISSN: 0967-5868
DOI: 10.1016/j.jocn.2019.01.053
Popis: The present study was examined the antioxidant effect of tamoxifen, a synthetic non-steroidal antiestrogen, on cromakalim or nicorandil (ATP-sensitive K+ (KATP) channels opener)-enhanced hydroxyl radical ( OH) generation induced by 1-methyl-4-phenylpyridinium ion (MPP+) in extracellular fluid of rat striatum. Rats were anesthetized, and sodium salicylate in Ringer's solution (0.5 mM or 0.5 nmol/µl/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. Cromakalim (100 µM) or nicorandil (1 mM) enhanced the formation of OH trapped as DHBA induced by MPP+ (5 mM). Concomitantly, these drugs enhanced dopamine (DA) efflux induced by MPP+. Tamoxifen (30 µM) significantly decreased the level of DA enhanced by cromakalim or nicorandil. Tamoxifen suppressed DHBA formation induced by MPP+ and cromakalim or nicorandil. When iron(II) was administered to cromakalim treated animals, a marked elevation of DHBA was observed, compared with the tamoxifen-treated rats These results indicated that the effects of tamoxifen on opening of KATP channels enhances OH generation in the extracellular space of striatum during of DA release by MPP+. These results indicated that estrogen protects against neuronal degeneration by as an anti-oxidant.
Databáze: OpenAIRE
Externí odkaz: