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. 2023 Jul 11;11(7):1955.
doi: 10.3390/biomedicines11071955.

Biosynthesized Selenium Nanoparticles Using Epigallocatechin Gallate Protect against Pentylenetetrazole-Induced Acute Epileptic Seizures in Mice via Antioxidative, Anti-Inflammatory, and Anti-Apoptotic Activities

Barakat M Alrashdi  1 , Alaa Fehaid  2 , Rami B Kassab  3 , Sara Rizk  4 , Ola A Habotta  2 , Ahmed E Abdel Moneim  5
Affiliations

Biosynthesized Selenium Nanoparticles Using Epigallocatechin Gallate Protect against Pentylenetetrazole-Induced Acute Epileptic Seizures in Mice via Antioxidative, Anti-Inflammatory, and Anti-Apoptotic Activities

Barakat M Alrashdi et al. Biomedicines. .

Abstract

Several negative outcomes are associated with current anti-epileptic medications. Epigallocatechin gallate (EGCG) is a plant-derived compound called catechin and has many medicinal activities, such as anti-inflammatory and antioxidant activities. Biosynthesized selenium nanoparticles are also showing their neuroprotective effect. The anti-epileptic effect of EGCG, alone or with SeNPs, is still debated. Here, we aimed to investigate the potential anti-seizure effect of biosynthesized SeNPs using EGCG (EGCG-SeNPs) against epileptic seizures and hippocampal damage, which is enhanced by pentylenetetrazole (PTZ) injection in mice. Mice were grouped as follows: control; PTZ-exposed group (epileptic model); EGCG + PTZ-treated group; sodium selenite (Na2SeO3) + PTZ-treated group; EGCG-SeNPs + PTZ-treated group; and valproic acid (VPA) + PTZ-treated group. EGCG-SeNPs administration showed anti-epileptic activity by increasing the latency time and reducing the seizure duration following the PTZ injection. Additionally, EGCG-SeNPs counteracted the PTZ-induced changes in oxidants and antioxidants. Moreover, EGCG-SeNPs inhibited the inflammatory response by suppressing the release of pro-inflammatory cytokines and decreasing the immunoreactivity of the glial fibrillary acidic protein and mRNA expression of glutamate receptor subunit zeta-1 (NMDAR; Grin1), showing their inhibitory effect on epilepsy-associated inflammation. Moreover, EGCG-SeNPs reduced PTZ-induced neuronal apoptosis, as indicated by a reduction in the levels of pro-apoptotic proteins and an elevation of the anti-apoptotic protein. Moreover, EGCG-SeNPs administration significantly modulated the PTZ-induced changes in monoamine levels and acetylcholinesterase activity in the hippocampal tissue. The obtained findings suggest the anti-seizure activity of EGCG-SeNPs via their antioxidant, anti-inflammatory, and anti-apoptotic effects, along with their neuromodulatory effect.

Keywords: apoptosis; epigallocatechin gallate; epilepsy; inflammation; mice; oxidative stress; selenium nanoparticles.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The characterization of the developed nanoformulation EGCG-SeNPs. (A) zeta sizer; (B) zeta potential and (C) TEM.
Figure 2
Figure 2
Effects of oral administration of epigallocatechin gallate (EGCG), sodium selenite (Na2SeO3), and biosynthesized SeNPs using EGCG (EGCG-SeNPs) on the seizure’s duration (A), latency (B), and scores (C) after the induction of epileptic seizures using pentylenetetrazol (PTZ). $ indicates a significant difference (p < 0.05) compared to the PTZ-exposed group. Data present the mean ± standard deviation (SD).
Figure 3
Figure 3
Antioxidant activities of oral administration of epigallocatechin gallate (EGCG), sodium selenite (Na2SeO3), and biosynthesized SeNPs using EGCG (EGCG-SeNPs) on PTZ-induced hippocampal oxidative damage. Levels of oxidants were indicated by lipid peroxidation (LPO, (A)), nitric oxide (NO, (B)), 8-hydroxy-2-deoxyguanosine (8OHdG, (C)), and glutathione (GSH, (D)). Antioxidants’ levels were indicated by superoxide dismutase (SOD, (E)), catalase (CAT, (F)), glutathione peroxidase (GPx, (G)), glutathione reductase (GR, (H)), and mRNA expression of the nuclear factor erythroid 2-related factor 2 (Nfe212, (I)). # and $ indicate significant differences (p < 0.05) compared to the control and PTZ-exposed groups, respectively. Data present the mean ± standard deviation (SD).
Figure 4
Figure 4
Anti-inflammatory activities of oral administration of epigallocatechin gallate (EGCG), sodium selenite (Na2SeO3), and biosynthesized SeNPs using EGCG (EGCG-SeNPs) on the PTZ-induced neuro-inflammation. Protein levels of tumor necrosis factor-α (TNF-α; (A)), interleukin-1β (IL-1β; (B)), and mRNA expression of NOS2 (C) were assessed as inflammation enhancers. # and $ indicate significant differences (p < 0.05) compared to the control and PTZ-exposed groups, respectively. Data present the mean ± standard deviation (SD).
Figure 5
Figure 5
Anti-apoptotic activities of oral administration of epigallocatechin gallate (EGCG), sodium selenite (Na2SeO3), and biosynthesized SeNPs using EGCG (EGCG-SeNPs) on PTZ-induced neuronal apoptosis. Hippocampal levels of anti-apoptotic (Bcl-2; (A)) and pro-apoptotic proteins [Bax (B) and caspase-3 (C)] were measured in all groups. # and $ indicate significant differences (p < 0.05) compared to the control and PTZ-exposed groups, respectively. Data present the mean ± standard deviation (SD).
Figure 6
Figure 6
Effects of oral administration of epigallocatechin gallate (EGCG), sodium selenite (Na2SeO3), and biosynthesized SeNPs using EGCG (EGCG-SeNPs) on PTZ-induced neuronal dysfunction. mRNA expression of glutamate receptor subunit zeta-1 (NMDAR; (A)), protein levels of glial fibrillary acidic protein (GFAP; (B)), and brain-derived neurotrophic factor (BDNF; (C)) were measured in hippocampal tissue and compared to pentylenetetrazole (PTZ)-induced changes. # and $ indicate significant differences (p < 0.05) compared to the control and PTZ-exposed groups, respectively. Data present the mean ± standard deviation (SD).
Figure 7
Figure 7
The immunoreactivity of glial fibrillary acidic protein (GFAP) in the hippocampal tissues in different treated groups. (A) Control group; (B): PTZ-treated group; (C) EGCG + PTZ-treated group; (D) Na2SeO3 + PTZ-treated group; (E) EGCG-SeNPs + PTZ-treated group; and (F) VPA + PTZ-treated group. magnifications = ×400. GFAPs are denoted by arrows; scale bar = 100 nm.
Figure 8
Figure 8
Effects of oral administration of epigallocatechin gallate (EGCG), sodium selenite (Na2SeO3), and biosynthesized SeNPs using EGCG (EGCG-SeNPs) on the PTZ-induced histopathological changes in the hippocampal tissue. (A) Control group; (B) PTZ-treated group; (C) EGCG + PTZ-treated group; (D) Na2SeO3 + PTZ-treated group; (E) EGCG-SeNPs + PTZ-treated group; and (F) VPA + PTZ-treated group. magnifications = ×400. White arrows indicate apoptotic neurons, white stars indicate pyknotic neurons, black arrows indicate necrotic neurons, and blue arrows indicate degenerated neurons. Scale bar = 100 nm.
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