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J Biochem Mol Toxicol ; 30(7): 360-9, 2016 Jul.
Article in English | MEDLINE | ID: mdl-27252111

ABSTRACT

Autophagy is necessary for neuronal homeostasis and its dysfunction has been implicated in Parkinson's disease (PD) as it can exacerbate endoplasmic reticulum (ER) stress and ER stress-induced apoptosis. Quercetin is a flavonoid known for its neuroprotective and antioxidant effects. The present study investigated the protective, autophagy-modulating effects of quercetin in the rotenone rat model of PD. Rotenone was intraperitoneally injected at dose of 2 ml/kg/day for 4 weeks. Simultaneous intraperitoneal injection of quercetin was given at a dose of 50 mg/kg/day also for 4 weeks. Neurobehavioral changes were studied. Oxidative/antioxidant status, C/EBP homologous protein (CHOP), Beclin-1, and dopamine levels were assessed. DNA fragmentation and histopathological changes were evaluated. This research work revealed that quercetin significantly attenuated rotenone-induced behavioral impairment, augmented autophagy, ameliorated ER stress- induced apoptosis with attenuated oxidative stress. From the current study, quercetin can act as an autophagy enhancer in PD rat model and modulates the microenvironment that leads to neuronal death.


Subject(s)
Antioxidants/pharmacology , Autophagy/drug effects , Catalepsy/drug therapy , Cognitive Dysfunction/drug therapy , Neuroprotective Agents/pharmacology , Parkinsonian Disorders/drug therapy , Quercetin/pharmacology , Animals , Beclin-1/genetics , Beclin-1/metabolism , Body Weight/drug effects , Catalepsy/chemically induced , Catalepsy/genetics , Catalepsy/physiopathology , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/genetics , Cognitive Dysfunction/physiopathology , Dopamine/metabolism , Endoplasmic Reticulum/drug effects , Endoplasmic Reticulum/metabolism , Endoplasmic Reticulum/pathology , Endoplasmic Reticulum Stress/drug effects , Gene Expression Regulation , Injections, Intraperitoneal , Male , Oxidative Stress , Parkinsonian Disorders/chemically induced , Parkinsonian Disorders/genetics , Parkinsonian Disorders/physiopathology , Rats , Rotenone , Signal Transduction , Thioredoxin-Disulfide Reductase/genetics , Thioredoxin-Disulfide Reductase/metabolism , Transcription Factor CHOP/genetics , Transcription Factor CHOP/metabolism
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