Protective Effects of Synthesis Compounds for Rotenone Neurotoxicity

Background: Rotenone, a natural pesticide, and insecticide is a specific inhibitor of complex I of the mitochondrial respiratory chain. Many studies have demonstrated that systemic administration of rotenone induces selective degeneration of nigral DA neurons, alpha-synuclein aggregation, and Parkinson disease-like symptoms in animal models.Method: We completed a search using PUBMED, SCOPUS, and ISI databases on 12 May 2019 with the following keywords: rotenone and prevent, ameliorate, attenuate, protective. Results: The total number of references found after automatically and manually excluding duplicates was 252 references. After the primary and secondary screening, 72 articles selected. Regarding, various compounds showed protective effects against neurotoxicity of rotenone such as D2 receptors (ropinirole), valproic acid, Sitagliptin, Liraglutide, Duloxetine, Pramipexole, Cilostazol, Febuxostat, Calcipotriol, Nicardipine, Diltiazem, Verapamil and so on.Discussion: Generally, the protective effects of these compounds create via various signaling pathways as autophagy activation, antiapoptotic, antioxidation, and anti-inflammatory effects. These compounds play essential roles in neuronal cell survival and demonstrated several neuroprotective effects via various signaling pathways such as protecting dopaminergic neuronal cells against oxidative damage, regulation tyrosine hydroxylase in the substantia nigra and reversed dopamine (DA) content, inhibition of NF-κB activation via regulating phosphorylation. The significant protective effects of these mediated through the ameliorated of a-synuclein aggregation because of dopaminergic neuronal. α-synuclein cumulation leads to inducing intracellular Ca+2, ROS, and stress oxidative. Also, disordering in homeostatic ionic Ca2+ homeostasis results in PD and dyskinesia.Conclusion There is a requirement of well-designed clinical trials to prove the clinical indications of these for the treatment of neurodegenerative disorders.

Keywords:

rotenone , neurotoxicity , synthesis compounds , Parkinson disease