eISSN: 1509-572x
ISSN: 1641-4640
Folia Neuropathologica
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SCImago Journal & Country Rank
2/2019
vol. 57
 
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abstract:
Original paper

Neuroprotective effect of nilotinib on pentylenetetrazol-induced epilepsy in adult rat hippocampus: involvement of oxidative stress, autophagy, inflammation, and apoptosis

Ghalia Mahfouz Attia
1, 2
,
Rasha Ahmed Elmansy
3, 4
,
Wael M. Elsaed
1, 5

1.
Department of Anatomy, Faculty of Medicine, Taibah University, Madinah, Kingdom of Saudi Arabia
2.
Department of Histology and Cell Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
3.
Department of Anatomy and Embryology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
4.
Department of Anatomy, Faculty of Medicine, Unaizah College of Medicine, Al Qassim University, Kingdom of Saudi Arabia
5.
Anatomy and Embryology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
Folia Neuropathol 2019; 57 (2): 146-160
Online publish date: 2019/05/08
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Introduction
Neuronal cell death and glial cell activation are the main pathological findings induced by seizures secondary to oxidative stress. Previous studies have explained neuronal cell death on the basis of cell necrosis and apoptosis. Recent studies have attributed the neuronal loss to autophagy. The proved antioxidant and antifibrotic effect of nilotinib favours its use in the management of epileptic seizures.

Aim of the study
was to analyse the neuroprotective and antiepileptic effect of nilotinib and explain its mechanism of action.

Material and methods
Forty adult male rats were divided into four groups: control, pentylenetetrazol (PTZ) group (injected with PTZ 60 mg/kg, s.c.), pregabalin (Pregb)-PTZ group (pretreated with pregabalin daily 30 mg/kg; orally for 1 week) and nilotinib (NIL)-PTZ group (pretreated with nilotinib, 25 mg/kg daily for 1 week) prior to PTZ. Seizure latency was evaluated, the hippocampus tissue level of antioxidant enzymes was assessed. The histopathological changes in the hippocampus were studied using hematoxylin and eosin stain and immunohistochemical stain for brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), beclin-1, nuclear factor kappa-B (NF-κB) and Bcl-2-like protein 4 (BAX).

Results
Nilotinib induced an increase in the latency of seizures, enhanced the antioxidant levels of the γ-aminobutyric acid and nuclear factor (erythroid-derived 2)-like 2 activities together with the improvement of the hippocampal histology. A reduction was reported for BDNF, GFAP, beclin-1, NF-κB and BAX expression in nerve cells.

Conclusions
Nilotinib may have promising neuroprotective and antiepileptic effects against pentylenetetrazolinduced seizures through promoting the antioxidant, antifibrotic, anti-inflammatory, antiapoptotic pathways and inhibiting autophagy.

keywords:

autophagy, apoptosis, hippocampus, epilepsy, nilotinib

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