Neuroprotective effect of the iron chelator desferrioxamine against MPP+ toxicity on striatal dopaminergic terminals.
Microdialysis was used to evaluate the effect of desferrioxamine (DES) against 1-methyl-4-phenylpyridinium (MPP+) toxicity. The presence of DES (40 fmol-40 nmol/15 min for a total of 90 min) in the Ringer solution, coperfused with MPP+ (40 nmol/15 min) on day 1, produced on day 2 a higher extracellular dopamine output after perfusion of MPP+ than in control MPP+ perfusion experiments, in which no DES was administered on day 1. Both Ringer perfusion alone (control Ringer) and coperfusion of 40 nmol DES with 40 nmol MPP+ on day 1 produced on day 2 similar increases in extracellular dopamine 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 800 fmol FeCl3/15 min along with 40 nmol MPP+ and 400 fmol DES on day 1 completely abolished on day 2 the neuroprotective effect found with 40 nmol MPP+ and 400 fmol DES; 800 fmol FeCl3 did not increase the neurotoxic effect of 40 nmol MPP+ perfusion. The ability of DES to protect against MPP+ toxicity may indicate a therapeutic strategy in the treatment of diseases when iron is implicated.
Santiago
M
M
Departamento de Bioquímica, Bromatología y Toxicología, Facultad de Farmacia, Universidad de Sevilla, Spain.
Matarredona
E R
ER
Granero
L
L
Cano
J
J
Machado
A
A
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology / Q000633:toxicity; D015259:Dopamine Agents / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D007501:Iron / Q000737:chemistry; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000737:chemistry; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010477:Perfusion; D017729:Presynaptic Terminals / Q000737:chemistry / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017262:Siderophores / Q000494:pharmacology*
D002614:Chelating Agents; D015259:Dopamine Agents; D018696:Neuroprotective Agents; D017262:Siderophores; D007501:Iron; D003676:Deferoxamine; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine