Effect of desferrioxamine, a strong iron (III) chelator, on 1-methyl-4-phenylpyridinium ion (MPP+)-induced hydroxyl radical generation in the rat striatum.
The present study was examined that the desferrioxamine, a strong iron (III) chelator, enhanced 1 methyl-4-phenylpyridinium ion (MPP+)-induced hydroxyl radical (*OH) generation in the extracellular fluid of caudate nucleus anesthetized rats. Rats were anesthetized, and sodium salicylate in Ringer's solution (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. Induction of desferrioxamine (50 microM) drastically increased the formation of *OH trapped as 2,3-DHBA by the action of MPP+, as compared with MPP+-only-treated animals. Although desferrioxamine did not change the levels of MPP+-induced dopamine, a marked elevation of *OH formation trapped as 2,3-DHBA was observed. When corresponding experiments were performed with reserpinized animals, the level of dopamine and 2,3-DHBA drastically decreased. However, the level of dopamine did not change, but desferrioxamine significantly increased the level of 2,3-DHBA in reserpinized animals. Iron (III) decreased MPP+-induced 2,3-DHBA formations in the presence of dopamine (10 microM). Moreover, when iron (II) was administered to desferrioxamine-treated animals, a marked elevation of 2,3-DHBA was observed, compared with MPP+-only-treated animals, that showed a positive linear correlation between iron (II) and *OH formation trapped as 2,3-DHBA (R2=0.981) in the dialysate. The present study indicates that the suppression of MPP+-induced *OH formation by iron (III) may play a key role in protective effect of iron (III) on the rat brain.
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*; D000818:Animals; D002412:Cations; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D005290:Ferric Compounds / Q000378:metabolism*; D017665:Hydroxyl Radical / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D051381:Rats; D017208:Rats, Wistar
D002412:Cations; D005290:Ferric Compounds; D007502:Iron Chelating Agents; D017665:Hydroxyl Radical; D003676:Deferoxamine; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine