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

Abstract

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 Kassab8 1Department of Emergency, The First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province 450000, People’s Republic of China; 2Department of ICU, Sunshine Union Hospital, Weifang City, Shandong Province 261000, People’s Republic of China; 3Department of Ophthalmology, Zhengzhou Second Hospital, Zhengzhou City, Henan Province 450000, People’s Republic of China; 4Department of Pharmacy, Central Hospital Affiliated to Shandong First Medical University, Jinan City, Shandong Province 250013, People’s Republic of China; 5Biology Department, Faculty of Science and Arts, Al Baha University, Almakhwah, Saudi Arabia; 6Laboratory Technology Department, College of Technological Studies, Safat 13092, Kuwait; 7Forensic Medicine and Toxicology Department, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Egypt; 8Department of Zoology and Entomology, Faculty of Science, Helwan University, Helwan 11795, EgyptCorrespondence: Lubo GuoDepartment of Pharmacy, Central Hospital Affiliated to Shandong First Medical University, Jinan City, Shandong Province 250013, People’s Republic of ChinaTel [phone]Email [email protected]: 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: epilepsy, selenium nanoparticles, oxidative stress, neuroinflammation and apoptosis, monoamines, GABA and glutamate

Keywords

• epilepsy
• selenium nanoparticles
• oxidative stress
• neuroinflammation and apoptosis
• monoamines
• gaba and glutamate.