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) 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 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.