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L-deprenyl protects against rotenone-induced, oxidative stress-mediated dopaminergic neurodegeneration in rats

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Title L-deprenyl protects against rotenone-induced, oxidative stress-mediated dopaminergic neurodegeneration in rats
 
Creator Saravanan, KS
Sindhu, KM
Senthilkumar, KS
Mohanakumar, KP
 
Subject Biochemistry & Molecular Biology; Neurosciences
 
Description The present study investigated oxidative damage and neuroprotective effect of the antiparkinsonian drug, L-deprenyl in neuronal death produced by intranigral infusion of a potent mitochondrial complex-I inhibitor, rotenone in rats. Unilateral stereotaxic intranigral infusion of rotenone caused significant decrease of striatal dopamine levels as measured employing HPLC-electrochemistry, and loss of tyrosine hydroxylase immunoreactivity in the perikarya of ipsilateral substantia nigra. (SN) neurons and their terminals in the striatum. Rotenone-induced increases in the salicylate hydroxylation products, 2,3- and 2,5-dihydroxybenzoic acid indicators of hydroxyl radials in mitochondrial P-2 fraction were dose-dependently attenuated by L-deprenyl. L-deprenyl (0.1-10 mg/kg; i.p.) treatment dose-dependently attenuated rotenone-induced reductions in complex-I activity and glutathione (GSH) levels in the SN, tyrosine hydroxylase inummoreactivity in the striatum or SN as well as striatal dopamine. Amphetamine-induced stereotypic rotations in these rats were also significantly inhibited by deprenyl administration. The rotenone-induced elevated activities of cytosolic antioxidant enzymes superoxide dismutase and catalase showed further significant increase following L-deprenyl. Our findings suggest that unilateral intranigral infusion of rotenone reproduces neurochemical, neuropathological and behavioral features of PD in rats and L-deprenyl can rescue the dopaminergic neurons from rotenone-mediated neurodegeneration in them. These results not only establish oxidative stress as one of the major causative factors underlying dopaminergic neurodegeneration as observed in Parkinson's disease, but also support the view that deprenyl is a potent free radical scavenger and an antioxidant. (c) 2006 Elsevier Ltd. All rights reserved.
 
Publisher PERGAMON-ELSEVIER SCIENCE LTDOXFORDTHE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
 
Date 2011-09-20T12:12:12Z
2011-09-20T12:12:12Z
2006
 
Type Review
 
Identifier NEUROCHEMISTRY INTERNATIONAL
0197-0186
http://hdl.handle.net/123456789/14172
 
Language English