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J Pharm Pharmacol ; 71(8): 1271-1281, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31144300

RESUMO

OBJECTIVE: To investigate the effect of desferrioxamine (DFO) and dextromethorphan (DXM) combination in animal model of Parkinson's disease (PD). METHODS: The PD was induced in rats through intracerebroventricular administration of 6-hydroxydopamine (6-OHDA) using stereotaxic apparatus. The animals were subjected to behavioural assessments and neurobiochemicals estimation followed by immunohistochemistry staining of neuron specific enolase (NSE) in striatum. KEY FINDINGS: Desferrioxamine and DXM combination has significantly reversed the catalepsy behaviour and elevated the antioxidant enzymes (SOD, CAT, GSH) and dopamine levels. Interestingly, the level of glutamate, nitric oxide, cytokines (IL-1ß, TNF-α) and NSE expressions were found to be decreased in striatum region of 6-OHDA-administered rats. The combination of DFO and DXM has shown synergism in most of the parameters studied, when compared to per se treatment. CONCLUSIONS: The reversal of catalepsy behaviour represents the protective effect of above combination on dopamine neurons in striatum from 6-OHDA toxicity. The mechanism of DFO and DXM combination might be attributed through attenuation of glutamate-induced excitotoxicity in neurons through ameliorating the reactive oxygen species and pro-inflammatory cytokines release. Treatment with DFO and DXM combination could control the multiple events in the pathogenesis of PD.


Assuntos
Catalepsia/tratamento farmacológico , Corpo Estriado/efeitos dos fármacos , Desferroxamina/farmacologia , Dextrometorfano/farmacologia , Ácido Glutâmico/metabolismo , Hidroxidopaminas/farmacologia , Animais , Antioxidantes/farmacologia , Catalepsia/metabolismo , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Dopamina/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Combinação de Medicamentos , Sinergismo Farmacológico , Masculino , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Ratos , Ratos Wistar
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