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. 2020 Aug 24:15:6339-6353.
doi: 10.2147/IJN.S259134. eCollection 2020.

Selenium Nanoparticles Pre-Treatment Reverse Behavioral, Oxidative Damage, Neuronal Loss and Neurochemical Alterations in Pentylenetetrazole-Induced Epileptic Seizures in Mice

Xiaona Yuan  1 , Zhenshuai Fu  2 , Pengfei Ji  3 , Lubo Guo  4 , Ali O Al-Ghamdy  5 , Ali Alkandiri  4   6 , Ola A Habotta  7 , Ahmed E Abdel Moneim  8 , Rami B Kassab  8
Affiliations

Selenium Nanoparticles Pre-Treatment Reverse Behavioral, Oxidative Damage, Neuronal Loss and Neurochemical Alterations in Pentylenetetrazole-Induced Epileptic Seizures in Mice

Xiaona Yuan et al. Int J Nanomedicine. .

Abstract

Introduction: Epilepsy is a chronic neurological condition characterized by behavioral, molecular, and neurochemical alterations. Current antiepileptic drugs are associated with various adverse impacts. The main goal of the current study is to investigate the possible anticonvulsant effect of selenium nanoparticles (SeNPs) against pentylenetetrazole (PTZ)-mediated epileptic seizures in mice hippocampus. Sodium valproate (VPA) was used as a standard anti-epileptic drug.

Methods: Mice were assigned into five groups (n=15): control, SeNPs (5 mg/kg, orally), PTZ (60 mg/kg, intraperitoneally), SeNPs+PTZ and VPA (200 mg/kg)+PTZ. All groups were treated for 10 days.

Results: PTZ injection triggered a state of oxidative stress in the hippocampal tissue as represented by the elevated lipoperoxidation, heat shock protein 70 level, and nitric oxide formation while decreased glutathione level and antioxidant enzymes activity. Additionally, the blotting analysis showed downregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in the epileptic mice. A state of neuroinflammation was recorded following the developed seizures represented by the increased pro-inflammatory cytokines. Moreover, neuronal apoptosis was recorded following the development of epileptic convulsions. At the neurochemical level, acetylcholinesterase activity and monoamines content were decreased in the epileptic mice, accompanied by high glutamate and low GABA levels in the hippocampal tissue. However, SeNP supplementation was found to delay the onset and decreased the duration of tonic, myoclonic, and generalized seizures following PTZ injection. Moreover, SeNPs were found to provide neuroprotection through preventing the development of oxidative challenge via the upregulation of Nrf2 and HO-1, inhibiting the inflammatory response and apoptotic cascade. Additionally, SeNPs reversed the changes in the activity and levels of neuromodulators following the development of epileptic seizures.

Conclusion: The obtained results suggest that SeNPs could be used as a promising anticonvulsant drug due to its potent antioxidant, anti-inflammatory, and neuromodulatory activities.

Keywords: GABA and glutamate; epilepsy; monoamines; neuroinflammation and apoptosis; oxidative stress; selenium nanoparticles.

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Conflict of interest statement

The authors report no conflict of interests in this work.

Figures

Figure 1
Figure 1
The histogram of size distribution measured by a Malvern Zetasizer.
Figure 2
Figure 2
Effect of selenium nanoparticles (SeNPs) on pro-oxidants level [malondialdehyde (MDA) and nitric oxide (NO)], heat shock protein 70 (Hsp70), glutathione (GSH) level in the hippocampal tissue following pentylenetetrazole (PTZ) injection. Results are figured as mean ± SD (n = 10); significant change was recorded following analysis with Duncan’s test as a post hoc test (P < 0.05). #Represents a significant change against the control mice; $Represents a significant change against the PTZ-injected mice.
Figure 3
Figure 3
Effect of selenium nanoparticles (SeNPs) on mRNA and activity of antioxidant enzymes [glutathione peroxidase (GPx, Gpx1), glutathione reductase (GR, Gsr), superoxide dismutase (SOD, Sod2) and catalase (CAT, Cat)] in the hippocampal tissue following pentylenetetrazole (PTZ) injection. Biochemical results are figured as mean ± SD (n = 10); significant change was recorded following analysis with Duncan’s test as a post hoc test (P < 0.05). #Represents a significant change against the control mice; $Represents a significant change against the PTZ-injected mice. qRT-PCR results are presented as mean ± SD of triplicate assays.
Figure 4
Figure 4
Effect of selenium nanoparticles (SeNPs) on the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in the hippocampal tissue following pentylenetetrazole (PTZ) injection. #Represents a significant change against the control mice; $Represents a significant change against the PTZ-injected mice.
Figure 5
Figure 5
Effect of selenium nanoparticles (SeNPs) on inflammatory markers TNF-α and IL-1β in the hippocampal tissue following pentylenetetrazole (PTZ) injection. Results are figured as mean ± SD (n = 10); significant change was recorded following analysis with Duncan’s test as a post hoc test (P < 0.05). #Represents a significant change against the control mice; $Represents a significant change against the PTZ-injected mice.
Figure 6
Figure 6
Effect of selenium nanoparticles (SeNPs) on apoptotic markers Bax, caspase-3 and Bcl2 in the hippocampal tissue following pentylenetetrazole (PTZ) injection. Results are figured as mean ± SD (n = 10); significant change was recorded following analysis with Duncan’s test as a post hoc test (P < 0.05). #Represents a significant change against the control mice; $Represents a significant change against the PTZ-injected mice.
Figure 7
Figure 7
Effect of selenium nanoparticles (SeNPs) on dopamine (DA), norepinephrine (NE) and serotonin (5-HT) in the hippocampal tissue following pentylenetetrazole (PTZ) injection. Results are figured as mean ± SD (n = 10); significant change was recorded following analysis with Duncan’s test as a post hoc test (P < 0.05). #Represents a significant change against the control mice; $Represents a significant change against the PTZ-injected mice.
Figure 8
Figure 8
Effect of selenium nanoparticles (SeNPs) on acetylcholinesterase activity (AChE), GABA and glutamate levels in the hippocampal tissue following pentylenetetrazole (PTZ) injection. Results are figured as mean ± SD (n = 10); significant change was recorded following analysis with Duncan’s test as a post hoc test (P < 0.05). #Represents a significant change against the control mice; $Represents a significant change against the PTZ-injected mice.
Figure 9
Figure 9
Effect of selenium nanoparticles (SeNPs) on hippocampal histological deformations following pentylenetetrazole (PTZ) injection. Scale bar = 100 μm. (A) Control group, (B) SeNPs group, (C) PTZ-injected group, (D) Co-treated group with SeNPs and PTZ, and (E) Co-treated group with sodium valproate (VPA) and PTZ. Degenerated neuron (white arrow). Scale bar = 80 μm.
Figure 10
Figure 10
Schematic diagram shows the protective role of selenium nanoparticles (SeNPs) against epileptic model induced by pentylenetetrazole (PTZ).
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