Introduction: 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.

The abundant use of lead (Pb; toxic heavy metal) worldwide has increased occupational and ecosystem exposure, with subsequent negative health effects. The flavonoid luteolin (LUT) found in many natural foodstuffs possesses antioxidant and anti-inflammatory properties. Herein, we hypothesized that LUT could mitigate liver damage induced by exposure to lead acetate (PbAc). Male Wistar rats were allocated to four groups: control group received normal saline, LUT-treated group (50 mg/kg, oral, daily), PbAc-treated group (20 mg/kg, i.p., daily), and LUT+PbAc-treated group (received the aforementioned doses via the respective routes of administration); the rats were treated for 7 days. The results revealed that PbAc exposure significantly increased hepatic Pb residue and serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin value. Oxidative reactions were observed in the liver tissue following PbAc intoxication, characterized by the depletion and downregulation of antioxidant proteins (glutathione, glutathione reductase, glutathione peroxidase, superoxide dismutase, catalase, nuclear factor erythroid 2-related factor 2, and heme oxygenase-1), and an increase in oxidants (malondialdehyde and nitric oxide). Additionally, PbAc increased the release and expression of the pro-inflammatory cytokines (tumor necrosis factor alpha and interleukin-1 beta), inducible nitric oxide synthase, and nuclear factor kappa B. Moreover, PbAc enhanced hepatocyte loss by increasing the expression of pro-apoptotic proteins (Bax and caspase-3) and downregulating the anti-apoptotic protein (Bcl-2). The changes in the aforementioned parameters were further confirmed by noticeable histopathological lesions. LUT supplementation significantly reversed all of the tested parameters in comparison with the PbAc-exposed group. In conclusion, our findings describe the potential mechanisms involved in the alleviation of PbAc-induced liver injury by luteolin via its potent anti-inflammatory, antioxidant, and anti-apoptotic properties.

Purpose: Selenium nanoparticles (SeNPs) have recently gained much attention in nanomedicine applications owing to their unique biological properties. Biosynthesis of SeNPs using nutraceuticals as lycopene (LYC) maximizes their stability and bioactivities. In this context, this study aimed to elucidate the renoprotective activity of SeNPs coated with LYC (LYC-SeNPs) in the acute kidney injury (AKI) model. Methods: Rats were divided into six groups: control, AKI (glycerol-treated), AKI+sodium selenite (Na₂SeO₃; 0.5 mg/kg), AKI+LYC (10 mg/kg), AKI+LYC-SeNPs (0.5 mg/kg) and treated for 14 days. Results: Glycerol treatment evoked significant increases in rhabdomyolysis-related markers (creatine kinase and LDH). Furthermore, relative kidney weight, Kim-1, neutrophil gelatinase-associated lipocalin (NGAL), serum urea, and creatinine in the AKI group were elevated. Glycerol-injected rats displayed declines in reduced glutathione level, and superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activities, paralleled with downregulations in Nfe2l2 and Hmox-1 expressions and high renal MDA and NO contents. Glycerol-induced renal inflammation was evident by rises in TNF-α, IL-1β, IL-6, and upregulated Nos2 expression. Also, apoptotic (elevated caspase-3, Bax, and cytochrome-c with lowered Bcl-2) and necroptotic (elevated Pipk3 expression) changes were reported in damaged renal tissue. Co-treatment with Na₂SeO₃, LYC, or LYC-SeNPs restored the biochemical, molecular, and histological alterations in AKI. In comparison with Na₂SeO₃ or LYC treatment, LYC-SeNPs had the best nephroprotective profile. Conclusion: Our findings authentically revealed that LYC-SeNPs co-administration could be a prospective candidate against AKI-mediated renal damage via antioxidant, anti-inflammatory, anti-apoptotic and anti-necroptotic activities.