Neuroprotective Mechanisms of Three Natural Antioxidants on a Rat Model of Parkinson’s Disease: A Comparative Study
Lyubka Tancheva, Maria Lazarova, Albena Alexandrova, Stela Dragomanova, Ferdinando Nicoletti, Elina Tzvetanova, Yordan Hodzhev, Reni Kalfin, Simona Miteva, Emanuela Mazzon, Nikolay Tzvetkov, Atanas G. Atanasov
Abstract
We compared the neuroprotective action of three natural bio-antioxidants (AOs): ellagic acid (EA), α-lipoic acid (LA), and myrtenal (Myrt) in an experimental model of Parkinson's disease (PD) that was induced in male Wistar rats through an intrastriatal injection of 6-hydroxydopamine (6-OHDA). The animals were divided into five groups: the sham-operated (SO) control group; striatal 6-OHDA-lesioned control group; and three groups of 6-OHDA-lesioned rats pre-treated for five days with EA, LA, and Myrt (50 mg/kg; intraperitoneally- i.p.), respectively. On the 2nd and the 3rd week post lesion, the animals were subjected to several behavioral tests: apomorphine-induced rotation; rotarod; and the passive avoidance test. Biochemical evaluation included assessment of main oxidative stress parameters as well as dopamine (DA) levels in brain homogenates. The results showed that all three test compounds improved learning and memory performance as well as neuromuscular coordination. Biochemical assays showed that all three compounds substantially decreased lipid peroxidation (LPO) levels, and restored catalase (CAT) activity and DA levels that were impaired by the challenge with 6-OHDA. Based on these results, we can conclude that the studied AOs demonstrate properties that are consistent with significant antiparkinsonian effects. The most powerful neuroprotective effect was observed with Myrt, and this work represents the first demonstration of its anti-Parkinsonian impact.