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 (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 K_ATP 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.