Sodium salicylate protects against rotenone-induced Parkinsonism in rats

Authors

  • Sindhu K. Madathil,

    1. Division of Cell Biology and Physiology, Laboratory of Clinical and Experimental Neuroscience, CSIR-Indian Institute of Chemical Biology, Kolkata, West Bengal, India
    Current affiliation:
    1. Spinal Cord and Brain Injury Research Center, University of Kentucky, B416 Biomedical and Biological Sciences Research Building, Lexington, KY
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    • S.K.M. and. S.S.K. contributed equally to this work.

  • Saravanan S. Karuppagounder,

    1. Division of Cell Biology and Physiology, Laboratory of Clinical and Experimental Neuroscience, CSIR-Indian Institute of Chemical Biology, Kolkata, West Bengal, India
    Current affiliation:
    1. Department of Neurology and Neuroscience, Weill Medical College of Cornell University, Burke Medical Research Institute, White Plains, NY
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    • S.K.M. and. S.S.K. contributed equally to this work.

  • Kochupurackal P. Mohanakumar

    Corresponding author
    • Division of Cell Biology and Physiology, Laboratory of Clinical and Experimental Neuroscience, CSIR-Indian Institute of Chemical Biology, Kolkata, West Bengal, India
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  • No conflicts of interest declared for any authors.

Correspondence to: K.P. Mohanakumar, Division of Cell Biology and Physiology, Laboratory of Clinical and Experimental Neuroscience, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Kolkata 700032, West Bengal, India. E-mail: mohankumar@iicb.res.in/kpmohanakumar@yahoo.com

ABSTRACT

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- (24–48h) 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. Synapse 67:502–514, 2013. © 2013 Wiley Periodicals, Inc.

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