Protective effects of Auranofin on the 6-hydroxydopamine model of Parkinson's disease in rats
1 Federal University of Piaui, CSHNB, Picos, Brazil.
2 Faculty of Medicine Estácio of Juazeiro do Norte, Ceará, Brazil.
3 Institute of Biology, University of Brasilia, Brasilia, DF, Brazil.
4 Department of Biology, University of British Columbia Okanagan Campus, Kelowna, BC, Canada.
5 Department of Physiology and Pharmacology, Faculty of Medicine of the Federal University of Ceará, Ceará, Brazil.
Research Article
World Journal of Biology Pharmacy and Health Sciences, 2023, 13(03), 106–119.
Article DOI: 10.30574/wjbphs.2023.13.3.0111
Publication history:
Received on 17 January 2023; revised on 07 March 2023; accepted on 10 March 2023
Abstract:
Auranofin (AU) presents anti-inflammatory effects and was shown to have a neuroprotective action. The objectives were to investigate the actions of AU in the 6-OHDA model of Parkinson’s disease (PD). Methods: Male Wistar rats were distributed into sham-operated (SO, control), untreated 6-OHDA lesioned and 6-OHDA lesioned, and treated with AU (3 and 10 mg/kg, p.o. for 2 weeks) groups. Then, animals were euthanized, the striatum dissected and processed for measurements of dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), as well as immunohistochemical assays for inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and the Nuclear factor erythroid 2-related factor 2 (Nrf2). The influence of AU on the activation of the brain NrF2 was also pursued by molecular docking experiments. Results: While the 6-OHDA lesioned rats presented a decrease in the striatal DA and DOPAC concentrations, these effects were prevented after AU treatment. The 6-OHDA group showed increased expressions of iNOS and COX-2 and these effects were highly prevented by AU. While Nrf2 expression was significantly decreased in the 6-OHDA lesioned animals, values came back to those close to the SO group after AU treatment. Auranofin may bind to the Kelch domain of the Kelch-like ECH-associated Protein 1 (Keap1) and possibly inhibit Keap1/Nrf2 interaction. Significance: AU by decreasing iNOS and COX-2 expressions and by increasing the expression of Nrf2, emerge as a potential neuroprotective drug for the treatment of PD.
Keywords:
Parkinson’s disease; 6-OHDA; Patients; Oxidative stress; Neuroinflammation, Transcription factor; Auranofin
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