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/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. Induction of desferrioxamine (50 μM) 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 μM). 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.