Novel action of vinpocetine in the prevention of paraquat-induced parkinsonism in mice: involvement of oxidative stress and neuroinflammation

摘要

Parkinson's disease (PD) is a multifactorial chronic progressive neurodegenerative disease caused by age, genetic and environmental factors such as paraquat (PQT). PQT (a quartenary nitrogen herbicide) is implicated in some form of idiopathic PD. This study sought to investigate the protective effect of vinpocetine on paraquat-induced Parkinsonism in mice. Forty-eight male albino mice were randomly divided into 6 groups and treated orally as follows for 21 days; Group 1: vehicle normal (10 ml/kg), group 2: vehicle control (10 ml/kg); groups 3-5: vinpocetine (5, 10 or 20 mg/kg); group 6: vinpocetine (20 mg/kg). Animals in groups 2-5 were given PQT (10 mg/kg, i.p.) every 3 days for 3 weeks. The effect of treatments on spontaneous motor activity (open field test), muscle coordination (rotarod tests), cataleptic behaviour (bar test), and working memory (Y-maze test) were assayed. After the behavioural assay on day 21, the midbrain was isolated for estimation of oxidative stress and TNF-alpha. Intraperitoneal injection of paraquat significantly induced motor deficits, muscle incoordination, catalepsy and working memory impairment which was ameliorated by the pretreatment of mice with vinpocetine. In addition, paraquat injection caused marked increase in nitroso-oxidative stress markers with concomitant deficits in antioxidant enzymes activities (GSH and SOD) as well as induction of tumour necrotic factor-alpha (TNF-alpha) in the mid-brain which were attenuated by the pretreatment of mice with vinpocetine. Findings from this study showed that vinpocetine prevented paraquat-induced motor deficits, memory impairment, oxidative stress and neuroinflammation through enhancement of antioxidant defense system and inhibition of neuroinflammatory cytokine. Thus, could be a potential drug in the management of Parkinsonism.