salicylates and Parkinson-Disease--Secondary

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.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 3,4-Dihydroxyphenylacetic Acid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Count; Disease Models, Animal; Dopamine; Dopamine Agents; Dose-Response Relationship, Drug; Free Radical Scavengers; Homovanillic Acid; Immunohistochemistry; Male; Mice; Mice, Inbred C57BL; Neostriatum; Neurons; Parkinson Disease, Secondary; Protective Agents; Salicylates; Substantia Nigra; Synaptic Transmission; Tyrosine 3-Monooxygenase

The effect of protection of dopaminergic neurons by talipexole, a dopamine (DA) agonist, is investigated on a methamphetamine (MA)-induced parkinsonism model of mice (C57BL/6N). The reduction of tyrosine hydroxylase activity in the striatum 72 h after MA (5 mg/kg every 2 h, four times) treatment was attenuated by the administration of talipexole (0.25 mg/kg or 1.0 mg/kg) prior to the administration of MA. In an in vitro experiment, talipexole inhibited the adduction reaction of hydroxyl radicals to salicylate. Taken together, these data suggest that the protective effect of talipexole on DA neurons is, in part, caused by the hydroxyl radical-scavenging action of the drug.

Topics: Animals; Azepines; Central Nervous System Stimulants; Chromatography, High Pressure Liquid; Dopamine; Dopamine Agonists; Enzyme Induction; Free Radical Scavengers; Gentisates; Hydroxybenzoates; Hydroxyl Radical; Male; Methamphetamine; Mice; Mice, Inbred C57BL; Nerve Tissue Proteins; Neurons; Neuroprotective Agents; Parkinson Disease, Secondary; Receptors, Dopamine D2; Salicylates; Salicylic Acid; Tyrosine 3-Monooxygenase

Topics: Adult; Antiparkinson Agents; Chlorpromazine; Drug Hypersensitivity; Extrapyramidal Tracts; Female; Handwriting; Humans; Male; Mental Disorders; Neurologic Examination; Parkinson Disease; Parkinson Disease, Secondary; Physostigmine; Salicylates; Schizophrenia; Substance-Related Disorders; Time Factors; Trifluoperazine; Tropanes