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

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.

PMID: 35336729
PMCID: PMC8945383
DOI: 10.3390/biology11030354

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

Naif E Al Omairi et al. Biology (Basel). 2022.

. 2022 Feb 23;11(3):354.

doi: 10.3390/biology11030354.

Authors

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.

PMID: 35336729
PMCID: PMC8945383
DOI: 10.3390/biology11030354

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.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

**Figure 1**
Effects of orally administered prodigiosin (PDG), sodium selenite (Na₂SeO₃), and green biosynthesized SeNPs with PDG (SeNPs-PDG) on the hippocampal levels of (A) reactive oxygen species (ROS), (B) malondialdehyde (MDA), (C) nitric oxide (NO), (D) glutathione (GSH), (E) glutathione peroxidase (GPx), (F) glutathione reductase (GR), (G) superoxide dismutase (SOD), and (H) catalase (CAT) following pentylenetetrazole (PTZ)-induced epileptic seizures. ^a and ^b denote significant differences (p < 0.05) compared with the untreated control and PTZ-injected groups, respectively. All records are presented as the mean ± standard deviation (SD).

**Figure 2**
Effects of orally administered prodigiosin (PDG), sodium selenite (Na₂SeO₃), and green biosynthesized SeNPs with PDG (SeNPs-PDG) on the mRNA expression levels of *Nrf2* in hippocampal tissue following pentylenetetrazole (PTZ)-induced epileptic seizures. ^a and ^b denote significant differences (p < 0.05) compared with the untreated control and PTZ-injected groups, respectively. All records are presented as the mean ± standard deviation (SD).

**Figure 3**
Effects of orally administered prodigiosin (PDG), sodium selenite (Na₂SeO₃), and green biosynthesized SeNPs with PDG (SeNPs-PDG) on the levels of inflammatory mediators, including (A) TNF-α, (B) IL-1β, (C) Cox-2, (D) *Nos2* mRNA expression, and (E) NF-κB in hippocampal tissue following pentylenetetrazole (PTZ)-induced epileptic seizures. ^a and ^b denote significant differences (p < 0.05) compared with the untreated control and PTZ-injected groups, respectively. All results are presented as the mean ± standard deviation (SD).

**Figure 4**
Effects of orally administered prodigiosin (PDG), sodium selenite (Na₂SeO₃), and green biosynthesized SeNPs with PDG (SeNPs-PDG) on the levels of apoptosis markers, including (A) caspase-3, (B) Bax, (C) Bcl-2, (D) mitochondrial cytochrome c, and (E) cytosolic cytochrome c in hippocampal tissue following pentylenetetrazole (PTZ)-induced epileptic seizures. ^a and ^b denote significant differences (p < 0.05) compared with the untreated control and PTZ-injected groups, respectively. All results are presented as the mean ± standard deviation (SD).

**Figure 5**
Effects of orally administered prodigiosin (PDG), sodium selenite (Na₂SeO₃), and green biosynthesized SeNPs with PDG (SeNPs-PDG) on (A) BDNF and (B) *Creb-1* mRNA expression levels in hippocampal tissue following pentylenetetrazole (PTZ)-induced epileptic seizures. ^a and ^b denote significant differences (p < 0.05) relative to the untreated control and PTZ-injected groups, respectively. All results are presented as the mean ± standard deviation (SD).

**Figure 6**
Effect of orally administered prodigiosin (PDG), sodium selenite (Na₂SeO₃), and prodigiosin-conjugated with selenium nanoparticles (SeNPs-PDG) on histopathological changes top panel for hippocampus at ×200, middle panel for hippocampus at ×400, and bottom panel for GFAP expression (×400) in the hippocampal tissue following PTZ-induced epileptic seizures.

See this image and copyright information in PMC

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

Full Text Sources

Research Materials