Aspirin and Salicylate Protect Against MPTP-Induced Dopamine Depletion in Mice
| Autor: | Olivier Curet, Annie Deffois, Nadine Aubin, C.J. Carter |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
Serotonin Dopamine Pharmacology Biochemistry Dexamethasone Body Temperature Mice Cellular and Molecular Neuroscience chemistry.chemical_compound Diclofenac Hydroxybenzoates medicine Animals Cyclooxygenase Inhibitors Monoamine Oxidase Aspirin biology Hydroxyl Radical business.industry Lysine MPTP MPTP Poisoning Ibuprofen Corpus Striatum Salicylates Mice Inbred C57BL chemistry 1-Methyl-4-phenyl-1 2 3 6-tetrahydropyridine Anesthesia biology.protein Cyclooxygenase Monoamine oxidase B Salicylic Acid business Salicylic acid Synaptosomes medicine.drug |
| Zdroj: | ResearcherID |
| ISSN: | 1471-4159 0022-3042 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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