Desferrioxamine and dextromethorphan combination exhibited synergistic effect and reversed the catalepsy behaviour in 6-hydroxydopamine hydroydopamine administered rats through regulating brain glutamate levels.
Animals
Antioxidants
/ pharmacology
Catalepsy
/ drug therapy
Corpus Striatum
/ drug effects
Deferoxamine
/ pharmacology
Dextromethorphan
/ pharmacology
Disease Models, Animal
Dopamine
/ metabolism
Dopaminergic Neurons
/ drug effects
Drug Combinations
Drug Synergism
Glutamic Acid
/ metabolism
Hydroxydopamines
/ pharmacology
Male
Neuroprotective Agents
/ pharmacology
Parkinson Disease
/ drug therapy
Rats
Rats, Wistar
catalepsy
cytokines
excitotoxicity
glutamate
striatum
synergism
Journal
The Journal of pharmacy and pharmacology
ISSN: 2042-7158
Titre abrégé: J Pharm Pharmacol
Pays: England
ID NLM: 0376363
Informations de publication
Date de publication:
Aug 2019
Aug 2019
Historique:
received:
25
01
2019
accepted:
05
05
2019
pubmed:
31
5
2019
medline:
20
12
2019
entrez:
31
5
2019
Statut:
ppublish
Résumé
To investigate the effect of desferrioxamine (DFO) and dextromethorphan (DXM) combination in animal model of Parkinson's disease (PD). 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. 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-1β, 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. 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.
Substances chimiques
Antioxidants
0
Drug Combinations
0
Hydroxydopamines
0
Neuroprotective Agents
0
Glutamic Acid
3KX376GY7L
Dextromethorphan
7355X3ROTS
Deferoxamine
J06Y7MXW4D
Dopamine
VTD58H1Z2X
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1271-1281Informations de copyright
© 2019 Royal Pharmaceutical Society.