Involvement of iron in MPP+ toxicity in substantia nigra: protection by desferrioxamine.

Desferrioxamine (DES) protective effect against 1-methyl-4-phenylpyridinium (MPP+) toxicity was evaluated by microdialysis in the substantia nigra. DES (1 microM to 10 mM) co-perfused with MPP+ (2.5 mM) on day 1, produced on day 2 a higher dopamine extracellular output after perfusion of MPP+ than in control-MPP+ perfusion experiments, in which no DES was administered on day 1. Both Ringer's perfusion alone (control-Ringer) and co-perfusion of DES (10 mM) with MPP+ (2.5 mM) on day 1 produced on day 2 similar increases in dopamine extracellular output after a second MPP+ perfusion. In the control-Ringer experiment, note that the MPP+ on day 2 is the first MPP+ perfusion. Perfusion of FeCl3 (200 microM) along with MPP+ (2.5 mM) and DES (100 microM) on day 1 completely abolished on day 2 the neuroprotective effect found with MPP+ (2.5 mM) and DES (100 microM). The ability of DES to protect against MPP+ toxicity may indicate a therapeutic strategy in the treatment of diseases when iron is implicated.