Neuroprotection by sodium salicylate against 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine-induced neurotoxicity.
The potent dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP) is known to produce hydroxyl radicals (OH) in vitro and in vivo. Salicylate (SA) can hydroxylate itself to form 2,3- and 2,5-dihydroxybenzoic acid (DHBA) by utilizing OH. In the present study we investigated the OH scavenging action and neuroprotective effects, if any, of SA in mice treated with MPTP (30 mg/kg i.p. twice, 16 h apart). MPTP treatment resulted in in vivo generation of OH and nigral neuronal insult as evidenced by dopamine depletion in nucleus caudatus putamen (NCP). This also caused significant decrease in glutathione in substantia nigra (SN) and NCP. SA administration alone in mice did not affect total monoamine oxidase (MAO) or MAO-B activities of the mitochondrial fraction or the crude enzyme preparation from SN or NCP. Pre-treatment of these animals with SA (25-100 mg/kg, i.p.) resulted in dose-dependent production of 2,3- and 2,5-DHBA in NCP. SA administration prior to or following MPTP blocked the neurotoxin-induced behavioural dysfunction as well as glutathione and dopamine depletion on the 7th day indicating its potent neuroprotective action. The present study suggests that SA acts as a free radical scavenger in the brain and indicates its strength as a valuable neuroprotectant.
Mohanakumar
K P
KP
Laboratory of Neurochemistry, Division of Pharmacology and Experimental Therapeutics, Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Calcutta, India. iichbio@giasc101.vsnl.net.in
Muralikrishnan
D
D
Thomas
B
B
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced / Q000188:drug therapy; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology; D005841:Gentisates; D005978:Glutathione / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D020267:MPTP Poisoning / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008995:Monoamine Oxidase / Q000378:metabolism; D017072:Neostriatum / Q000187:drug effects / Q000201:enzymology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012980:Sodium Salicylate / Q000494:pharmacology*; D013378:Substantia Nigra / Q000187:drug effects / Q000201:enzymology
D016861:Cyclooxygenase Inhibitors; D015259:Dopamine Agents; D016166:Free Radical Scavengers; D005841:Gentisates; D062385:Hydroxybenzoates; D018696:Neuroprotective Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D017665:Hydroxyl Radical; C009135:2,3-dihydroxybenzoic acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008995:Monoamine Oxidase; D005978:Glutathione; C010925:2,5-dihydroxybenzoic acid; D004298:Dopamine; D012980:Sodium Salicylate; D006719:Homovanillic Acid