Allopurinol suppresses 2-bromoethylamine and 1-methyl-4-phenylpyridinium ion (MPP(+))-induced hydroxyl radical generation in rat striatum.
The present study was examined whether or not 2-bromoethyamine, a semicarbazide-sensitive amine oxidase (SSAO, EC; 1.4.3.6) inhibitor, would increase an active dopaminergic neurotoxin, 1-methyl-4-phenylpyridinium ion (MPP(+))-induced hydroxyl radical ((*)OH) generation in the rat striatum. Rats were anesthetized, and sodium salicylate (0.5 mM or 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 2-bromoethylamine (100 microM or 100 pmol/microl/min) into the striatum drastically increased the formation of (*)OH products, trapped as DHBA by the action of MPP(+). Further, I studied the effect of allopurinol, a xanthine oxidase inhibitor, an 2-bromoethylamine and MPP(+)-induced (*)OH generation. Allopurinol (10 microM or 10 pmol/microl/min) significantly suppressed 2-bromoethyamine and MPP(+)-induced (*)OH. These results suggest that a definite mechanism is not clear at the moment, after inhibition of tissue-bound and/or blood plasma SSAO activity, with consequent increases in bioactive amine levels, enhances the formation of (*)OH products of efflux/oxidation due to MPP(+).
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*; D000493:Allopurinol / Q000494:pharmacology*; D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005021:Ethylamines / Q000633:toxicity*; D017665:Hydroxyl Radical / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D005021:Ethylamines; C004504:2-bromoethylamine; D017665:Hydroxyl Radical; D000493:Allopurinol; D006631:Amine Oxidase (Copper-Containing); D015655:1-Methyl-4-phenylpyridinium