الفهرس 
Possible potential effect of agmatine in amelioration of L-dopa-induced dyskinesia in rats
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Abstract
Dyskinesia is characterized by abnormal involuntary movements (AIMs) that is still restrictive problem associated with chronic use of L-dopa in Parkinson’s disease (PD) treatment as the definite pathological mechanism involved is still unclear. However, there are correlation between excitotoxicity of glutamatergic NMDARs, neuroinflammation, and oxidative stress in the lesioned nigrostriatal pathway which mediate firing of basal ganglia neurons involved in dyskinesias.
The currentstudy investigated for the first time, the novel neuroprotective effect of agmatine in ameliorating both PD and dyskinesia focusing on its antioxidant, anti-inflammatory, and anti-apoptotic potentiality through Nrf2 activation and suppression of HMGB1/RAGE/TLR4/MyD88/NF-κB signaling pathway. PD is induced in animals by ten consecutive doses of rotenone (3mg/kg/day; s.c.), while agmatine (100mg/kg/day; i.p.) was injected for 16 days after modeling PD either alone or in combination with L-dopa/carbidopa (50/25mg/kg/day; i.p.).
Rotenone lesioned rats showed a statistically significant deteriorating effect on behavioral, neurochemical, histopathological, and immunochemical analysis. Moreover, dyskinesia observed in PD rats that received L-dopa was ameliorated by agmatine treatment. Agmatine improved animals’ behavior and abolished the AIMs, it inhibited NMDARs expression in nigral tissues leading to inhibition of inflammatory and oxidative stress cascades. It increased both nigral TH immunoreactive cells and striatal dopamine contents, besides increased antioxidant defense mechanism of Nrf2/TAC contents along with a significant decrease of HMGB1/RAGE /TLR4 /MyD88/NF-κB protein expression.
The current investigated data signified the novel role of agmatine in ameliorating both PD and dyskinesia through mediating NMDARs, Nrf2, and HMGB1/RAGE/TLR4/NF-κB signaling pathways.