Effects of metformin on apoptosis and α-synuclein in a rat model of pentylenetetrazole-induced epilepsy.

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 β-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 β-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.

authors

Hussein AM,Eldosoky M,El-Shafey M,El-Mesery M,Ali AN,Abbas KM,Abulseoud OA

doi

10.1139/cjpp-2018-0266

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

37-46

issue

1

eissn

0008-4212

issn

1205-7541

journal_volume

97

pub_type

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