Selenium Nanoparticles with Prodigiosin Rescue Hippocampal Damage Associated with Epileptic Seizures Induced by Pentylenetetrazole in Rats

Naif E Al Omairi; Ashraf Albrakati; Khalaf F Alsharif; Abdulraheem S Almalki; Walaa Alsanie; Zakaria Y Abd Elmageed; Dalia Zaafar; Maha S Lokman; Amira A Bauomy; Saied K Belal; Mohamed M Abdel-Daim; Ahmed E Abdel Moneim; Hussain Alyami; Rami B Kassab

doi:10.3390/biology11030354

Selenium Nanoparticles with Prodigiosin Rescue Hippocampal Damage Associated with Epileptic Seizures Induced by Pentylenetetrazole in Rats

Biology (Basel). 2022 Feb 23;11(3):354. doi: 10.3390/biology11030354.

Authors

Naif E Al Omairi¹, Ashraf Albrakati², Khalaf F Alsharif³, Abdulraheem S Almalki⁴, Walaa Alsanie³, Zakaria Y Abd Elmageed⁵, Dalia Zaafar⁶, Maha S Lokman^{7

8}, Amira A Bauomy⁹, Saied K Belal², Mohamed M Abdel-Daim^{10

11}, Ahmed E Abdel Moneim⁸, Hussain Alyami¹, Rami B Kassab^{8

12}

Affiliations

¹ Department of Internal Medicine, College of Medicine, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
² Department of Human Anatomy, College of Medicine, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
³ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia.
⁴ Department of Chemistry, Faculty of Science, Taif University, Taif 21974, Saudi Arabia.
⁵ Department of Pharmacology, Edward Via College of Osteopathic Medicine, University of Louisiana at Monroe, Monroe, LA 71203, USA.
⁶ Department of Pharmacology and Toxicology, Faculty of Pharmacy, Modern University for Technology and Information, Cairo 11311, Egypt.
⁷ Biology Department, College of Science and Humanities, Prince Sattam bin Abdul Aziz University, Alkharj 11942, Saudi Arabia.
⁸ Department of Zoology and Entomology, Faculty of Science, Helwan University, Cairo 11795, Egypt.
⁹ Department of Science Laboratories, College of Science and Arts, Qassim University, ArRass 52719, Saudi Arabia.
¹⁰ Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, P.O. Box 6231, Jeddah 21442, Saudi Arabia.
¹¹ Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt.
¹² Biology Department, Faculty of Science and Arts, Al-Baha University, Al-Mukhwah 65554, Saudi Arabia.

Abstract

Background: Prodigiosin (PDG) is a red pigment synthesized by bacterial species with important pharmaceutical and biological activities. Here, we investigated the neuroprotective and anticonvulsant activities of green biosynthesized selenium formulations with PDG (SeNPs-PDG) versus pentylenetetrazole (PTZ)-induced epileptic seizures.

Methods: Rats were assigned into six experimental groups: control; PTZ (60 mg/kg, epileptic model); sodium valproate (200 mg/kg) + PTZ; PDG (300 mg/kg) + PTZ; sodium selenite (0.5 mg/kg) + PTZ; and SeNPs-PDG (0.5 mg/kg) + PTZ. The treatment duration is extended to 28 days.

Results: SeNPs-PDG pre-treatment delayed seizures onset and reduced duration upon PTZ injection. Additionally, SeNPs-PDG enhanced the antioxidant capacity of hippocampal tissue by activating the expression of nuclear factor erythroid 2-related factor 2 and innate antioxidants (glutathione and glutathione derivatives, in addition to superoxide dismutase and catalase) and decreasing the levels of pro-oxidants (lipoperoxidation products and nitric oxide). SeNPs-PDG administration inhibited inflammatory reactions associated with epileptic seizure development by suppressing the production and activity of glial fibrillary acidic protein and pro-inflammatory mediators, including interleukin-1 beta, tumor necrosis factor-alpha, cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor kappa B. Moreover, SeNPs-PDG protected against hippocampal cell loss following PTZ injection by decreasing the levels of cytosolic cytochrome c, Bax, and caspase-3 and enhancing the expression of anti-apoptotic Bcl-2. Interestingly, SeNPs-PDG restored the PTZ-induced imbalance between excitatory and inhibitory amino acids and improved monoaminergic and cholinergic transmission.

Conclusions: These promising antioxidative, anti-inflammatory, anti-apoptotic, and neuromodulatory activities indicate that SeNPs-PDG might serve as a naturally derived anticonvulsant agent.

Keywords: apoptosis; epilepsy; neuroinflammation; neurotransmission; oxidative stress; prodigiosin; selenium nanoparticles.