Salicylate protects against MPTP-induced impairments in dopaminergic neurotransmission at the striatal and nigral level in mice.
The analgesic and anti-inflammatory drug sodium salicylate was studied for its potential protective effects in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. C 57BL/6 mice were treated with a single dose of sodium salicylate (50 mg/kg or 100 mg/kg i.p.) or saline immediately before injection of MPTP (30 mg/kg or 40 mg/kg s.c.) or saline. Analysis of striatal dopamine and metabolites as well as immunostaining for tyrosine hydroxylase of nigral sections was performed 7 days after MPTP treatment. MPTP (30 mg/kg) led to a strong decrease in striatal dopamine levels (1.87+/-0.27 ng/mg) compared to saline-treated controls (15.72+/-0.78 ng/mg), which was significantly attenuated by sodium salicylate 50 mg/kg and 100 mg/kg (5.59+/-0.56 ng/mg and 8.64+/-0.89 ng/mg, respectively). Remarkably, the MPTP-induced loss of tyrosine hydroxylase immunoreactivity in nigral cell bodies was nearly completely prevented by the higher dose of sodium salicylate. Furthermore, salicylate demonstrated radical scavenging effects in an in vitro Fenton system indicated by HPLC determination of the dihydroxylated reaction products of salicylate, namely, 2,3- and 2,5-dihydroxybenzoic acid. The protective effects of salicylate against reversible or irreversible impairments in dopaminergic neurotransmission after MPTP treatment may be related to its radical scavenging properties and other mechanisms which need to be clarified.
Ferger
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B
Institut für Pharmakologie und Toxikologie, Fachbereich Pharmazie, Philipps-Universität Marburg, Germany. ferger@mailer.uni-marburg.de
Teismann
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Earl
C D
CD
Kuschinsky
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K
Oertel
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WH
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects*; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002452:Cell Count / Q000187:drug effects; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology; D006719:Homovanillic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology; D012459:Salicylates / Q000494:pharmacology*; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015259:Dopamine Agents; D016166:Free Radical Scavengers; D020011:Protective Agents; D012459:Salicylates; D015102:3,4-Dihydroxyphenylacetic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine; D006719:Homovanillic Acid