Ameliorative effects of vanillin against pentylenetetrazole-induced epilepsy and associated memory loss in mice: The role of Nrf2/HO-1/NQO1 and HMGB1/RAGE/TLR4/NFκB pathways

International Immunopharmacology, Год журнала: 2024, Номер 129, С. 111657 - 111657

Опубликована: Фев. 9, 2024

Epilepsy is a severe neurological disorder associated with substantial morbidity and mortality. Vanillin (Van) natural phenolic aldehyde beneficial pharmacological properties. This study investigated the neuroprotective effects of Van in epilepsy elucidated its mechanism action. Swiss albino mice were divided into following five groups: "normal group", 0.9 % saline; "pentylenetetrazole (PTZ) intraperitoneal administration 35 mg/kg PTZ on alternate days up to 42 days; "PTZ + 20", 40", sodium valproate (Val)" groups received injections conjunction 20 mg, 40 mg/kg, Val 300 respectively. Behavioural tests hippocampal histopathological analysis performed all groups. The Nrf2/HO-1/NQO1 HMGB1/RAGE/TLR4/NFκB pathways, oxidative stress, neuro-inflammation, apoptotic markers analysed. Furthermore, brain acetylcholinesterase (AChE) activity levels dopamine (DA), gamma-aminobutyric acid GABA, serotonin 5-HT assessed. prolonged seizure manifestations improved electroencephalogram (EEG) criteria 100 once daily. increased levels, subsequent attenuation malondialdehyde (MDA) nitric oxide (NO) elevated glutathione (GSH) intensified superoxide dismutase (SOD) catalase activities. reduced gene protein expression decreased inflammatory markers. In addition, AChE activity, glial fibrillary acidic proteins (GFAP) neurotransmitter brain-derived neurotrophic factors (BDNF). By increasing downregulating HMGB1/RAGE/TLR4/ NFκB pathway, offered protection PTZ-kindled lipid peroxidation, upregulation antioxidant enzyme activities, reduction inflammation apoptosis.

Язык: Английский

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Behavioral and Biochemical Insights into the Therapeutic Potential of Mitocurcumin in a Zebrafish–Pentylenetetrazole (PTZ) Epilepsy Model

Pharmaceuticals, Год журнала: 2025, Номер 18(3), С. 382 - 382

Опубликована: Март 7, 2025

Background/Objectives: Epilepsy is a complex neurological disorder with strong link to oxidative stress, which contributes seizure susceptibility and neuronal damage. This study aims investigate the effects of curcumin (Cur), sodium valproate (VPA), mitocurcumin (MitoCur), mitochondria-targeted curcumin, on behavioral stress parameters in zebrafish model pentylenetetrazole (PTZ)-induced seizures. Methods: Adult were exposed two concentrations (0.25 0.5 µM for Cur MitoCur; 0.25 mM VPA). Behavioral assessments, including locomotion, spatial exploration, directional movement, conducted using EthoVision XT tracking software. Oxidative markers, superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GPx), total antioxidant status (TAS), analyzed brain homogenates. Results: analyses indicated dose-dependent effects, higher doses generally reducing activity. MitoCur at enhanced defenses reduced damage, while exhibited pro-oxidant shift. VPA improved TAS without significantly altering MDA levels. Conclusions: These findings emphasize importance dose optimization antioxidant-based epilepsy treatments highlight potential as targeted therapeutic option.

Язык: Английский

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Unveiling the role of histone deacetylases in neurological diseases: focus on epilepsy

Biomarker Research, Год журнала: 2024, Номер 12(1)

Опубликована: Ноя. 19, 2024

Abstract Epilepsy remains a prevalent chronic neurological disease that is featured by aberrant, recurrent and hypersynchronous discharge of neurons poses great challenge to healthcare systems. Although several therapeutic interventions are successfully utilized for treating epilepsy, they can merely provide symptom relief but cannot exert disease-modifying effect. Therefore, it urgent need explore other potential mechanism develop novel approach delay the epileptic progression. Since approximately 30 years ago, histone deacetylases (HDACs), versatile epigenetic regulators responsible gene transcription via binding histones or non-histone substrates, have grabbed considerable attention in drug discovery. There also substantial evidences supporting aberrant expressions and/activities HDAC isoforms reported epilepsy inhibitors (HDACi) been purposes this condition. However, specific mechanisms underlying role HDACs progression not fully understood. Herein, we reviewed basic information HDACs, summarized recent findings associated with roles diverse subunits discussed regulatory which affected development epilepsy. Additionally, provided brief discussion on as promising targets treatment, serving valuable reference study clinical translation field.

Язык: Английский

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Advances in Nanomedicines: A Promising Therapeutic Strategy for Ischemic Cerebral Stroke Treatment

Nanomedicine, Год журнала: 2024, Номер 19(9), С. 811 - 835

Опубликована: Март 6, 2024

Ischemic stroke, prevalent among the elderly, necessitates attention to reperfusion injury post treatment. Limited drug access brain, owing blood–brain barrier, restricts clinical applications. Identifying efficient carriers capable of penetrating this barrier is crucial. Blood–brain transporters play a vital role in nutrient transport brain. Recently, nanoparticles emerged as carriers, enhancing permeability via surface-modified ligands. This article introduces structure, elucidates pathogenesis, compiles ischemic stroke treatment drugs, explores nanomaterials for encapsulation and emphasizes their advantages over conventional drugs. Utilizing drug-delivery systems offers targeting efficiency benefits absent traditional The prospects nanomedicine are promising.

Язык: Английский

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Melatonin as an add-on treatment for epilepsy: A systematic review and meta-analysis

Seizure, Год журнала: 2024, Номер 117, С. 133 - 141

Опубликована: Фев. 23, 2024

Язык: Английский

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Insight into the Role of Ferroptosis in Epilepsy

Journal of Integrative Neuroscience, Год журнала: 2024, Номер 23(6), С. 113 - 113

Опубликована: Июнь 13, 2024

Excessively high or synchronized neuronal activity in the brain is underlying cause of epilepsy, a condition central nervous system. Epilepsy caused mostly by an imbalance inhibitory and excitatory neural networks. Recurrent prolonged seizures lead to death, which turn promotes epileptogenesis epileptic seizures. Ferrous ion-mediated cell death known as ferroptosis, due accumulation lipid peroxidation products resulting from compromise glutathione (GSH)-dependent antioxidant The pathophysiology epilepsy has been linked anomalies peroxidase 4 (GPX4)/GSH redox pathway, peroxidation, iron metabolism. Studies have shown that inhibiting ferroptosis may alleviate cognitive impairment decrease seizures, indicating it neuroprotective. With hope aiding development more novel approaches for management this research aimed examine role disease.

Язык: Английский

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Recent advances in nanotherapy-based treatment of epilepsy

Colloids and Surfaces B Biointerfaces, Год журнала: 2025, Номер 249, С. 114499 - 114499

Опубликована: Янв. 6, 2025

Язык: Английский

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Empagliflozin Mitigates PTZ-Induced Seizures in Rats: Modulating Npas4 and CREB-BDNF Signaling Pathway

Journal of Neuroimmune Pharmacology, Год журнала: 2025, Номер 20(1)

Опубликована: Янв. 7, 2025

Abstract Empagliflozin (EMPA) is one of the sodium/glucose cotransporter 2 (SGLT2) inhibitors that has been recently approved for treatment diabetes mellitus type II. Recently, EMPA shown protective effects in different neurological disorders, besides its antidiabetic activity. Kindling a relevant model to study epilepsy and neuroplasticity. This aimed investigate potential (1 3 mg/kg orally) against convulsant induced by pentylenetetrazole (PTZ) using modified window- (win-) PTZ kindling protocol. The biochemical dysfunction hippocampal damage were profoundly reversed dose-dependent manner, as evidenced significant increase reduced glutathione (GSH) decrease malondialdehyde (MDA) contents. Furthermore, counteracted PTZ-induced neuronal region, confirmed histopathological examination tissues. impaired astrocytosis showed an antiapoptotic effect through reduction glial fibrillary acidic protein (GFAP) BCL2-Associated X Protein (BAX) expressions, respectively. Interestingly, exhibited antiepileptic seizures significantly reducing PAS domain 4 (Npas4), cyclic adenosine monophosphate (cAMP) response element binding (CREB) enhancing brain-derived neurotrophic factor (BDNF)-tropomyosin receptor kinase B (TrkB) pathway, which are found be involved epileptogenesis, eventually leading improvement behavioral impairments PTZ. Hence, these results further prospective insights neuroprotective agent. Graphical

Язык: Английский

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Plasma metabolome reveals altered oxidative stress, inflammation, and amino acid metabolism in dogs with idiopathic epilepsy

Epilepsia, Год журнала: 2025, Номер unknown

Опубликована: Янв. 13, 2025

Abstract Objective Idiopathic epilepsy (IE) is the most common chronic neurological disease in dogs and an established natural animal model for human types with genetic unknown etiology. However, metabolic pathways underlying IE remain largely unknown. Methods Plasma samples of healthy ( n = 39) 49) were metabolically profiled 121 known target metabolites) fingerprinted 1825 untargeted features) using liquid chromatography coupled to mass spectrometry. Dogs classified as mild phenotype (MP; 22) or drug‐resistant (DR; 27). All received same standard adult maintenance diet a minimum 20 days (35 ± 11 days) before sampling. Data analyzed combination univariate (one‐way analysis variance Kruskal–Wallis rank sum test), multivariate limma , orthogonal partial least squares–discriminant analysis), pathway enrichment statistical analysis. Results In both DR MP IE, distinct plasma profile fingerprint compared was observed. Metabolic involved these alterations included oxidative stress, inflammation, amino acid metabolism. Moreover, significantly lower concentrations vitamin B6 found p .001) .005) dogs. Significance Our data provide new insights into dogs, further substantiating its potential humans epilepsy, reflected by related changes stress metabolites B6. Even more, several within uncovered offer promising therapeutic targets management primarily ultimately humans.

Язык: Английский

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Correlation between selenium levels and selenoproteins expression in idiopathic generalized epilepsy: a study from Karachi

BMC Neurology, Год журнала: 2025, Номер 25(1)

Опубликована: Янв. 23, 2025

Oxidative damage has been implicated in multiple neurodegenerative diseases, including epilepsy. Selenium, the form of selenoproteins is an integral part human antioxidant defense system. Though a relationship between altered selenium levels and epilepsy reported, limited evidence available about expression pattern epileptic patients. This study aimed to determine serum idiopathic healthy individuals. Expression profiling (GPx1, TRxR1 SEPW1) both at mRNA protein was also evaluated. Serum 30 patients with generalized their age gender matched controls were measured. Protein Glutathione Peroxidase 1 (GPx1), Thioredoxin Reductase (TRxR1) Selenoprotein W (SEPW1) estimated using ELISA. GPx1, SEPW1 determined qRT-PCR. The mean values for cases 37.6 ± 2.0 µmol/ml 38.9 2.7 µmol/ml, respectively. Selenium significantly lower as compared (p = 0.031). No statistically significant differences observed group. GPx1 found be down regulated (0.34 0.13 folds respectively) whereas SEPW 0.04 up subjects. deficiency suggests association provides information status Pakistani population helps understanding role prevention

Язык: Английский

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