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Antidepressant and Antioxidative Effect of Ibuprofen in the Rotenone Model of Parkinson’s Disease

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Abstract

Idiopathic Parkinson’s disease is a neurodegenerative disorder that affects approximately 1 % of the population over 55 years of age. The disease manifests itself through motor and nonmotor symptoms induced mainly by the neurodegeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The possible mechanisms involved in this pathology include mitochondrial dysfunction, neuroinflammation, and oxidative stress. The present study evaluated the effects of the nonselective cyclooxygenase inhibitor ibuprofen on motor and depressive-like behavior induced by rotenone in rats. Rotenone (2.5 mg/kg, i.p., for 10 days) decreased tyrosine hydroxylase immunoreactivity in the SNpc, and ibuprofen treatment (15 mg/kg, p.o., for 22 days) blocked this impairment. We also found that rotenone-induced motor deficits (hypolocomotion) and depressive-like behavior, and ibuprofen was able to reverse these deficits. In addition to motor and nonmotor behaviors, we evaluated oxidative stress induced by rotenone. Rotenone administration depleted glutathione levels in the hippocampus and reduced catalase activity in both the hippocampus and striatum. Post treatment with ibuprofen blocked the depletion of glutathione induced by rotenone and increased the basal levels of this antioxidant in the striatum. Ibuprofen also restored catalase activity. The neuroprotective effects of ibuprofen against toxicity induced by rotenone appear to be attributable to its antioxidant properties, in addition to cyclooxygenase inhibition.

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Acknowledgments

This work was supported by grants from CNPq, CAPES, and REUNI, which had no further role in the study design, in the collection, analysis, and interpretation of the data, in writing the report, or in the decision to submit the paper for publication. MABFV is a recipient of a CNPq fellowship.

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We declare that we have no conflicts of interest.

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Correspondence to Maria A. B. F. Vital.

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Zaminelli, T., Gradowski, R.W., Bassani, T.B. et al. Antidepressant and Antioxidative Effect of Ibuprofen in the Rotenone Model of Parkinson’s Disease. Neurotox Res 26, 351–362 (2014). https://doi.org/10.1007/s12640-014-9467-y

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  • DOI: https://doi.org/10.1007/s12640-014-9467-y

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