Effects of metformin on apoptosis and α-synuclein in a rat model of pentylenetetrazole-induced epilepsy.
Can J Physiol Pharmacol
; 97(1): 37-46, 2019 Jan.
Article
em En
| MEDLINE
| ID: mdl-30308130
ABSTRACT
The present study was designed to examine the possible neuroprotective and antiepileptic effects of metformin (Metf) in a rat model of pentylenetetrazole (PTZ)-induced epilepsy and its possible underlying mechanisms. Forty male albino rats were assigned to 4 groups of equal size (1) normal control (NC) group, (2) Metf group daily treatment with Metf (200 mg/kg, i.p.) for 2 weeks, (3) PTZ group treatment with PTZ (50 mg/kg, i.p.) every other day for 2 weeks, and (4) Metf + PTZ group daily treatment with PTZ and metformin (200 mg/kg, i.p.) for 2 weeks. Administration of PTZ caused a significant increase in seizure score and duration, induced a state of oxidative stress (high malondialdehyde, low reduced glutathione and catalase activity), and led to the upregulation of ß-catenin, caspase-3, and its cleavage products, Hsp70 and α-synuclein, in hippocampal regions as well as a significant reduction in seizure latency. While Metf treatment significantly ameliorated PTZ-induced seizures, attenuated oxidative stress, and upregulated α-synuclein and ß-catenin expression, it also inhibited caspase-3 activation and the release of the cleavage product and caused more upregulation in Hsp70 expression in hippocampal regions (p < 0.05). In conclusion, the antiepileptic and neuroprotective effects of Metf in PTZ-induced epilepsy might be due to the inhibition of apoptosis, attenuation of oxidative stress and α-synuclein expression, and upregulation of Hsp70.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pentilenotetrazol
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Apoptose
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Epilepsia
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Alfa-Sinucleína
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Metformina
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article