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

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.

Neurotherapeutic effects of prodigiosin conjugated with silver-nanoparticles in rats exposed to cadmium chloride-induced neurotoxicity

“…However, treatment with PG reduced the Cd-induced loss of neuronal cells as evidenced by a decrease in the production of pro-apoptotic proteins (Bax and caspase-3) and an increase in the expression of the anti-apoptotic protein Bcl-2. These findings are in agreement with those of Al Omairi, et al, (2022), who found that PG inhibited apoptosis in depressed rats. Lapenda et al (2020), recorded the anti-apoptotic action of PG and found that it inhibited the apoptotic cascade linked to stomach lesions brought on by injections of acidified ethanol by upregulating Bcl-2 and downregulating Bax and caspase-3.…”

Effects of Gryllus bimaculatus and Oxya chinensis sinuosa extracts on brain damage via blood-brain barrier control and apoptosis in mice with pentylenetetrazol-induced epilepsy

“…Since neurons are more sensitive to ROS injury during the early stages of brain development, an imbalance between ROS production and scavenging systems leads to neuronal damage. ROS-induced cytotoxicity is closely associated with and mostly precedes apoptotic cell death [ 9 , 43 ]. Interestingly, Gb and Ocs extracts protected hippocampal neurons and suppressed apoptosis associated with seizure propagation.…”

“…Oxidative stress is responsible for neuronal loss and death, which are directly related to epilepsy in in vitro animal models [ 9 , 10 ], and disturbs the antioxidant systems, including catalase (CAT), glutathione (GSH), superoxide dismutase (SOD), and lipid peroxidation (malondialdehyde [MDA]) systems [ 11 , 12 ]. Excess reactive oxygen species (ROS) activate pro-apoptotic signaling cascades, resulting in apoptotic cell death [ 13 ].…”

Effect of Blueberry Extract on Liver in Aged Rats

“…Although the precise mechanism is not understood, the production of inflammatory cytokines in hepatic tissues as a consequence of aging may be linked to the activation of NF- κ B signaling pathway. NF- κ B is a key transcription factor of M1 macrophages and is required for the induction of a large number of inflammatory genes, including those encoding TNF- α and IL-6 [ 48 ]. Thus, blueberry may exhibit its anti-inflammatory effects by suppressing the activation of NF- κ B signaling as revealed by our results, although further studies are required to prove this.…”