Neuroprotection by sodium salicylate against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity

Kochupurackal P. Mohanakumar, Dhanasekharan Muralikrishnan, Bobby Thomas

Research output: Contribution to journalArticle

101 Scopus citations

Abstract

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. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)281-290
Number of pages10
JournalBrain Research
Volume864
Issue number2
DOIs
StatePublished - May 12 2000

Keywords

  • Dopamine depletion
  • Free radical scavenger
  • Glutathione
  • Hydroxyl radicals
  • MPTP
  • Neuroprotection
  • Nucleus caudatus putamen
  • Salicylic acid

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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