Aspirin and salicylate protect against MPTP-induced dopamine depletion in mice.
The neurotoxic effects of the dopamine-selective neurotoxin MPTP (15 mg/kg, s.c.), in mice, were totally prevented by systemic administration of salicylate (ED50 = 40 mg/kg, i.p.), aspirin (ED50 = 60 mg/kg, i.p.), or the soluble lysine salt of aspirin, Aspegic (ED50 = 80 mg/kg, i.p.). The protective effects of aspirin are unlikely to be related to cyclooxygenase inhibition as paracetamol (100 mg/kg, i.p.), diclofenac (100 mg/kg, i.p.), ibuprofen (20 mg/kg, i.p.) and indomethacin (100 mg/kg, i.p.) were ineffective. Dexamethasone (3-30 mg/kg, i.p.), which, like aspirin and salicylate, has been reported to inhibit the transcription factor NF-kappaB, was also ineffective. Aspirin or salicylate (100 microM) had no effect on dopamine uptake into striatal synaptosomes or on monoamine oxidase B activity. The neuroprotective effects of salicylate derivatives could perhaps be related to hydroxyl radical scavenging. This was suggested by the fact that hydroxylated metabolites of salicylate (2,3- and 2,5-dihydrobenzoic acid) were recovered in brain tissue following the combined administration of MPTP and aspirin to a greater extent than following aspirin alone. The surprising neuroprotective effects of aspirin in an animal model of Parkinson's disease warrant further clinical investigation.
Aubin
N
N
Central Nervous System Research Department, Synthélabo Recherche, Bagneux, France.
Curet
O
O
Deffois
A
A
Carter
C
C
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors*; D000818:Animals; D001241:Aspirin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000633:toxicity; D001831:Body Temperature / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004298:Dopamine / Q000172:deficiency* / Q000378:metabolism; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical / Q000037:antagonists & inhibitors / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives / Q000494:pharmacology; D020267:MPTP Poisoning; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000187:drug effects / Q000378:metabolism; D012459:Salicylates / Q000494:pharmacology*; D020156:Salicylic Acid; D012701:Serotonin / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology
D016861:Cyclooxygenase Inhibitors; D062385:Hydroxybenzoates; D012459:Salicylates; D012701:Serotonin; D017665:Hydroxyl Radical; D003907:Dexamethasone; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008995:Monoamine Oxidase; D008239:Lysine; D020156:Salicylic Acid; D001241:Aspirin; D004298:Dopamine; C010395:acetylsalicylic acid lysinate