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L-deprenyl protects against rotenone-induced, oxidative stress-mediated dopaminergic neurodegeneration in rats.
Neurochem Int. 2006 Jul; 49(1):28-40.NI

Abstract

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 P2 fraction were dose-dependently attenuated by L-deprenyl. L-deprenyl (0.1-10mg/kg; i.p.) treatment dose-dependently attenuated rotenone-induced reductions in complex-I activity and glutathione (GSH) levels in the SN, tyrosine hydroxylase immunoreactivity 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.

Authors+Show Affiliations

Division of Clinical and Experimental Neuroscience, Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Calcutta 700032, India.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16490285

Citation

Saravanan, Karuppagounder S., et al. "L-deprenyl Protects Against Rotenone-induced, Oxidative Stress-mediated Dopaminergic Neurodegeneration in Rats." Neurochemistry International, vol. 49, no. 1, 2006, pp. 28-40.
Saravanan KS, Sindhu KM, Senthilkumar KS, et al. L-deprenyl protects against rotenone-induced, oxidative stress-mediated dopaminergic neurodegeneration in rats. Neurochem Int. 2006;49(1):28-40.
Saravanan, K. S., Sindhu, K. M., Senthilkumar, K. S., & Mohanakumar, K. P. (2006). L-deprenyl protects against rotenone-induced, oxidative stress-mediated dopaminergic neurodegeneration in rats. Neurochemistry International, 49(1), 28-40.
Saravanan KS, et al. L-deprenyl Protects Against Rotenone-induced, Oxidative Stress-mediated Dopaminergic Neurodegeneration in Rats. Neurochem Int. 2006;49(1):28-40. PubMed PMID: 16490285.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - L-deprenyl protects against rotenone-induced, oxidative stress-mediated dopaminergic neurodegeneration in rats. AU - Saravanan,Karuppagounder S, AU - Sindhu,Kizhakke M, AU - Senthilkumar,Karuppagounder S, AU - Mohanakumar,Kochupurackal P, Y1 - 2006/02/21/ PY - 2005/10/25/received PY - 2005/12/04/revised PY - 2005/12/20/accepted PY - 2006/2/24/pubmed PY - 2006/8/25/medline PY - 2006/2/24/entrez SP - 28 EP - 40 JF - Neurochemistry international JO - Neurochem Int VL - 49 IS - 1 N2 - 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 P2 fraction were dose-dependently attenuated by L-deprenyl. L-deprenyl (0.1-10mg/kg; i.p.) treatment dose-dependently attenuated rotenone-induced reductions in complex-I activity and glutathione (GSH) levels in the SN, tyrosine hydroxylase immunoreactivity 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. SN - 0197-0186 UR - https://www.unboundmedicine.com/medline/citation/16490285/L_deprenyl_protects_against_rotenone_induced_oxidative_stress_mediated_dopaminergic_neurodegeneration_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-0186(06)00023-4 DB - PRIME DP - Unbound Medicine ER -