TY - JOUR
T1 - 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
AU - Thomas, Bobby
AU - Saravanan, Karuppagounder S.
AU - Mohanakumar, Kochupurackal P.
N1 - Funding Information:
BT & KSS are recipients of the Council of Scientific & Industrial Research (CSIR) Senior Research Fellowships (SRF). The work was supported from National Bioscientist Award for Career Development (to KPM) from the Department of Biotechnology (DBT), Govt. of India.
PY - 2008/5
Y1 - 2008/5
N2 - 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.
AB - 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.
KW - Antioxidant enzymes
KW - Endogenous antioxidant molecules
KW - Experimental Parkinson's disease
KW - Ferrous citrate
KW - Free radical scavenger
KW - MPP-induced {radical dot}OH generation
KW - Neuroprotective therapy
KW - Oxidative stress
KW - Striatal dopamine depletion
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U2 - 10.1016/j.neuint.2007.10.012
DO - 10.1016/j.neuint.2007.10.012
M3 - Article
C2 - 18164516
AN - SCOPUS:40949144116
SN - 0197-0186
VL - 52
SP - 990
EP - 1001
JO - Neurochemistry International
JF - Neurochemistry International
IS - 6
ER -