In vitro and in vivo evidences that antioxidant action contributes to the neuroprotective effects of the neuronal nitric oxide synthase and monoamine oxidase-B inhibitor, 7-nitroindazole

Bobby Thomas, Karuppagounder S. Saravanan, Kochupurackal P. Mohanakumar

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

The neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole (7-NI) is neuroprotective against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism. Monoamine oxidase (MAO)-B inhibitory action partially contributes to this effect. We tested the hypothesis that 7-NI could be a powerful hydroxyl radical ({radical dot}OH) scavenger, and interferes with oxidative stress caused by MPTP. We measured {radical dot}OH, reduced glutathione (GSH), as well as superoxide dismutase (SOD) and catalase activities in the nucleus caudatus putamen and substantia nigra of Balb/c mice following MPTP and/or 7-NI administration. The nNOS inhibitor caused dose-dependent inhibition in the production of {radical dot}OH in (i) Fenton-like reaction employing ferrous citrate in a cell-free system in test tubes, (ii) in isolated mitochondrial preparation in presence of MPP+, and (iii) in the striatum of mice systemically treated with MPTP. An MPTP-induced depletion of GSH in both the nuclei was blocked by 7-NI, which was dose-dependent (10-50 mg/kg), but independent of MAO-B inhibition. The nNOS-mediated recovery of GSH paralleled attenuation of MPTP-induced depletion of striatal dopamine. MPTP-induced increase in the activities of striatal or nigral SOD and catalase were significantly attenuated by 7-NI treatment. These results suggest potent antioxidant action of 7-NI in its neuroprotective effects against MPTP-induced neurotoxicity.

Original languageEnglish (US)
Pages (from-to)990-1001
Number of pages12
JournalNeurochemistry International
Volume52
Issue number6
DOIs
StatePublished - May 1 2008

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Nitric Oxide Synthase Type I
Monoamine Oxidase Inhibitors
Monoamine Oxidase
Neuroprotective Agents
Antioxidants
Corpus Striatum
Substantia Nigra
Catalase
Superoxide Dismutase
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Cell-Free System
Caudate Nucleus
Putamen
Parkinsonian Disorders
4-phenyl-1,2,3,6-tetrahydropyridine
In Vitro Techniques
7-nitroindazole
Hydroxyl Radical
Glutathione
Dopamine

Keywords

  • Antioxidant enzymes
  • Endogenous antioxidant molecules
  • Experimental Parkinson's disease
  • Ferrous citrate
  • Free radical scavenger
  • MPP-induced {radical dot}OH generation
  • Neuroprotective therapy
  • Oxidative stress
  • Striatal dopamine depletion

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

In vitro and in vivo evidences that antioxidant action contributes to the neuroprotective effects of the neuronal nitric oxide synthase and monoamine oxidase-B inhibitor, 7-nitroindazole. / Thomas, Bobby; Saravanan, Karuppagounder S.; Mohanakumar, Kochupurackal P.

In: Neurochemistry International, Vol. 52, No. 6, 01.05.2008, p. 990-1001.

Research output: Contribution to journalArticle

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