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

The present study was examined the antioxidant effect of tamoxifen, a synthetic non-steroidal antiestrogen, on cromakalim or nicorandil (ATP-sensitive K+ (K-ATP) channels opener)-enhanced hydroxyl radical (center dot OH) generation induced by 1-methyl-4-phenylpyridinium ion (MPP+) in extracellular fluid of rat stria turn. Rats were anesthetized, and sodium salicylate in Ringer's solution (0.5 mM or 0.5 nmol/mu l/min) was infused through a microdialysis probe to detect the generation of center dot OH as reflected by the non-enzymatic formation of 2,3-dihydroxybenzoic acid (DHBA) in the striatum. Cromakalim (100 mu M) or nicorandil (1 mM) enhanced the formation of center dot OH trapped as DHBA induced by MPP+ (5 mM). Concomitantly, these drugs enhanced dopamine (DA) efflux induced by MPP+. Tamoxifen (30 PM) 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 K-ATP channels enhances center dot 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. (C) 2019 Published by Elsevier Ltd.