Aspirin protects striatal dopaminergic neurons from neurotoxin-induced degeneration: an in vivo microdialysis study.
The effect of aspirin on dopaminergic neuronal damage induced by in vivo infusion of 1-methyl-4-phenylpiridinium iodide (MPP(+)) and 6-hydroxydopamine (6-OHDA) was studied in rats, using microdialysis. Rat striata were perfused with 1 mM MPP(+) or 6-OHDA for 10 min, causing peak levels of dopamine (DA) in the dialytic fluid, after 40 min. After 24 h, 1 mM MPP(+) was perfused again for 10 min and DA levels measured in the dialytic fluid, as an index of neuronal cell integrity. Pretreatment with Aspidol (lysine acetylsalicylate), 180 mg/kg i.p., 1 h before MPP(+) or 6-OHDA perfusion, did not modify DA extracellular output, on day 1, but restored MPP(+)-induced DA release on day 2, indicating a neuroprotective effect of Aspidol. Conversion of 0.5 mM 4-hydroxybenzoic acid (4-HBA) to 3,4-dihydroxybenzoic acid (3,4-DHBA) was measured as an index of reactive oxygen species (ROS). 6-OHDA, but not MPP(+), significantly enhanced 3,4-DHBA levels in the perfusion fluid. Aspidol (180 mg/kg, i.p.) reduced 6-OHDA-dependent increase of 3,4-DHBA levels. Meloxicam (50 mg/kg, i.p.), a specific cyclooxygenase-2 (COX-2) inhibitor, was ineffective against both neurotoxins. These data suggest that the protective effect of aspirin is due to different mechanisms of action according to the neurotoxin used, and it is independent from COX-2 inhibition.
Di Matteo
Vincenzo
V
Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, 66030 Santa Maria Imbaro, Chieti, Italy. vdimatteo@negrisud.it
Pierucci
Massimo
M
Di Giovanni
Giuseppe
G
Di Santo
Angelo
A
Poggi
Andreina
A
Benigno
Arcangelo
A
Esposito
Ennio
E
D000704:Analysis of Variance; D000818:Animals; D001241:Aspirin / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology*; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D062385:Hydroxybenzoates / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D017551:Microdialysis / Q000379:methods; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009498:Neurotoxins; D051381:Rats; D017207:Rats, Sprague-Dawley; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D062385:Hydroxybenzoates; D018696:Neuroprotective Agents; D009498:Neurotoxins; C009091:protocatechuic acid; D014446:Tyrosine 3-Monooxygenase; D001241:Aspirin; D004298:Dopamine