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.
Matarredona
E R
ER
Departamento de Bioquimica, Bromatologia y Toxicologia, Facultad de Farmacia, Universidad de Sevilla, Spain.
Santiago
M
M
Cano
J
J
Machado
A
A
D015655:1-Methyl-4-phenylpyridinium / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000818:Animals; D002712:Chlorides; D003676:Deferoxamine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D005290:Ferric Compounds / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D002712:Chlorides; D005290:Ferric Compounds; D018696:Neuroprotective Agents; D003676:Deferoxamine; D015655:1-Methyl-4-phenylpyridinium; C024555:ferric chloride; D004298:Dopamine