Document Detail


Sodium salicylate protects against rotenone-induced parkinsonism in rats.
MedLine Citation:
PMID:  23447126     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Complex I deficiency culminating in oxidative stress is proposed as one of the upstream mechanisms of nigral neuronal death in Parkinson's disease. We investigated whether sodium salicylate, an active metabolite of aspirin, could afford protection against rotenone-induced oxidative stress, neuronal degeneration, and behavioral dysfunction in rats, because it has the potential to accept a molecule each of hydroxyl radical (•OH) at the third or fifth position of its benzyl ring. Rotenone caused dose-dependent increase in •OH in isolated mitochondria from the cerebral cortex and time- (24-48 h) and dose-dependent (0.1-100 µM) increase in the substantia nigra and the striatum, ipsilateral to the side of rotenone infusion. Administration of sodium salicylate at 12-h intervals for 4 days showed dose-dependent (50-100 mg/kg, i.p) reductions in the levels of •OH in the nigra on the fifth day. These animals showed significant attenuation in rotenone-induced loss in striatal dopamine levels, number of nigral dopaminergic neurons, reduced and oxidized glutathione levels, and complex I activity loss, but superoxide dismutase activity was increased further. Amphetamine- or apomorphine-induced ipsilateral rotations in rotenone-treated rats were significantly reduced in rats treated with sodium salicylate. Our results indicate a direct role of •OH in mediating nigral neuronal death by rotenone and confirm the neuroprotective potential of salicylate in a rodent model of parkinsonism.
Authors:
Sindhu K Madathil; Saravanan S Karuppagounder; Kochupurackal P Mohanakumar
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-03-27
Journal Detail:
Title:  Synapse (New York, N.Y.)     Volume:  67     ISSN:  1098-2396     ISO Abbreviation:  Synapse     Publication Date:  2013 Aug 
Date Detail:
Created Date:  2013-06-24     Completed Date:  2013-11-07     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  8806914     Medline TA:  Synapse     Country:  United States    
Other Details:
Languages:  eng     Pagination:  502-14     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Wiley Periodicals, Inc.
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MeSH Terms
Descriptor/Qualifier:
Amphetamine / pharmacology
Animals
Apomorphine / pharmacology
Corpus Striatum / cytology,  drug effects,  metabolism
Cyclooxygenase Inhibitors / pharmacology*,  therapeutic use
Dopamine / metabolism
Dose-Response Relationship, Drug
Electron Transport Complex I / metabolism
Glutathione / metabolism
Hydroxyl Radical / metabolism
Male
Neurons / metabolism
Oxidative Stress
Parkinsonian Disorders / chemically induced,  drug therapy*
Rats
Rats, Sprague-Dawley
Rotenone / toxicity*
Sodium Salicylate / pharmacology*,  therapeutic use
Substantia Nigra / cytology,  drug effects,  metabolism
Superoxide Dismutase / metabolism
Uncoupling Agents / toxicity*
Chemical
Reg. No./Substance:
0/Cyclooxygenase Inhibitors; 0/Uncoupling Agents; 03L9OT429T/Rotenone; 3352-57-6/Hydroxyl Radical; CK833KGX7E/Amphetamine; EC 1.15.1.1/Superoxide Dismutase; EC 1.6.5.3/Electron Transport Complex I; GAN16C9B8O/Glutathione; N21FAR7B4S/Apomorphine; VTD58H1Z2X/Dopamine; WIQ1H85SYP/Sodium Salicylate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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