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

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.

Geroprotective and Radioprotective Activity of Quercetin, (-)-Epicatechin, and Ibuprofen in Drosophila melanogaster

“…It must be noted that ibuprofen demonstrated the most significant antioxidant effect. Previously minor data demonstrated that this anti-inflammatory drug can exercise antioxidant properties predominantly through the COX inhibition (Milatovic et al, 2011; Zaminelli et al, 2014). However, this mechanism is absented in flies.…”

Translating GWAS Findings Into Therapies For Depression And Anxiety Disorders: Drug Repositioning Using Gene-Set Analyses Reveals Enrichment Of Psychiatric Drug Classes

“…Some repositioning hits for MDD-CONVERGE included oxotremorine-M, a muscarinic acetylcholine receptor agonist that may ameliorate depressive symptoms and restore hippocampal neurogenesis in an animal model 51 and capeserod, a 5-HT4 receptor agonist shown effective in a mouse model 52 . For MDD-PGC, top-listed drugs include three NSAIDs, namely ibuprofen, meclofenamate and flufenamic acid, which possess anti-inflammatory actions that may also be beneficial for depression 53,54 . Remarkably, our analysis recovered a known augmentation therapy for depression, namely Cytomel (or synthetic triiodothyronine [T3]) 55 .…”

Ibuprofen targets neuronal pentraxins expresion and improves cognitive function in mouse model of AlCl3-induced neurotoxicity

“…P<0.05 was considered to indicate a statistically significant difference. 3 -induced neurotoxicity mouse model. In order to analyze the pharmacological effects of ibuprofen on the learning and memory abilities of AlCl 3 -treated mice, ibuprofen (100 mg/kg/day) and AlCl 3 (150 mg/kg/day) were administered to the appropriate groups for 12 days, after which the mice were subjected to memory testing using the Morris water maze test for the final 7 days of treatment, prior to sacrifice.…”