Antiepileptic effect of fisetin in iron-induced experimental model of traumatic epilepsy in rats in the light of electrophysiological, biochemical, and behavioral observations

Das, Jharana; Singh, Rameshwar; Sharma, Deepak

doi:10.1080/1028415x.2016.1183342

Cited by 47 publications

(21 citation statements)

References 33 publications

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“…PTZ was solubilized in double-distilled water. Fisetin was administered at the doses that have been reported to inhibit the onset and progression of seizures in experimental animals in previous studies ( 41 , 42 ). For acute studies, fisetin was administered in doses of 5, 10, and 20 mg/kg body weight each day by oral (p.o.)…”

Section: Methodsmentioning

confidence: 99%

Neuroprotective Effect of Fisetin Through Suppression of IL-1R/TLR Axis and Apoptosis in Pentylenetetrazole-Induced Kindling in Mice

et al. 2021

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Epilepsy is a complex neurological disorder, characterized by frequent electrical activity in brain regions. Inflammation and apoptosis cascade activation are serious neurological sequelae during seizures. Fisetin (3, 3′,4′,7-tetrahydroxyflavone), a flavonoid molecule, is considered for its effective anti-inflammatory and anti-apoptotic properties. This study investigated the neuroprotective effect of fisetin on experimental epilepsy. For acute studies, increasing current electroshock (ICES) and pentylenetetrazole (PTZ)-induced seizure tests were performed to evaluate the antiseizure activity of fisetin. For the chronic study, the kindling model was established by the administration of PTZ in subconvulsive dose (25 mg/kg, i.p.). Mice were treated with fisetin (5, 10, and 20 mg/kg, p.o.) to study its probable antiseizure mechanism. The kindled mice were evaluated for seizure scores. Their hippocampus and cortex were assessed for neuronal damage, inflammation, and apoptosis. Histological alterations were observed in the hippocampus of the experimental mice. Levels of high mobility group box 1 (HMGB1), Toll-like receptor-4 (TLR-4), interleukin-1 receptor 1 (IL-1R1), interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) were assessed in the hippocampus and cortex by ELISA. The immunoreactivity and mRNA expressions of nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), cytochrome C, and caspase-3 were quantified by immunohistochemical analysis and real-time PCR. Phosphorylation ELISA was performed to evaluate AkT/mTOR (mammalian target of rapamycin) activation in the hippocampus and cortex of the kindled mice. The results showed that fisetin administration increased the seizure threshold current (STC) in the ICES test. In PTZ-induced seizures, fisetin administration increased the latency for myoclonic jerks (MJs) and generalized seizures (GSs). In the PTZ-induced kindling model, fisetin administration dose-dependently suppressed the development of kindling and the associated neuronal damage in the experimental mice. Further, fisetin administration ameliorated kindling-induced neuroinflammation as evident from decreased levels of HMGB1, TLR-4, IL-1R1, IL-1β, IL-6, and TNF-α in the hippocampus and cortex of the kindled mice. Also, the immunoreactivity and mRNA expressions of inflammatory molecules, NF-κB, and COX-2 were decreased with fisetin administration in the kindled animals. Decreased phosphorylation of the AkT/mTOR pathway was reported with fisetin administration in the hippocampus and cortex of the kindled mice. The immunoreactivity and mRNA expressions of apoptotic molecules, cytochrome C, and caspase-3 were attenuated upon fisetin administration. The findings suggest that fisetin shows a neuroprotective effect by suppressing the release of inflammatory and apoptosis molecules and attenuating histological alterations during experimental epilepsy.

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Section: Methodsmentioning

confidence: 99%

Neuroprotective Effect of Fisetin Through Suppression of IL-1R/TLR Axis and Apoptosis in Pentylenetetrazole-Induced Kindling in Mice

et al. 2021

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“…The iron ion model refers to the intracortical injection of iron ions into the sensorimotor cortex through stereotaxic surgery [ 42 , 43 ]. Ferrous chloride can promote lipid peroxidation, free radical formation, and abnormal glutamate transportation, mimicking TBI and recurrent PTE attacks [ 33 ].…”

Section: Generalized Tonic-clonic Seizure Modelsmentioning

confidence: 99%

Animal Models of Epilepsy: A Phenotype-oriented Review

Wang¹,

Wei²,

Feng³

et al. 2022

Aging and disease

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Epilepsy is a serious neurological disorder characterized by abnormal, recurrent, and synchronous discharges in the brain. Long-term recurrent seizure attacks can cause serious damage to brain function, which is usually observed in patients with temporal lobe epilepsy. Controlling seizure attacks is vital for the treatment and prognosis of epilepsy. Animal models, such as the kindling model, which was the most widely used model in the past, allow the understanding of the potential epileptogenic mechanisms and selection of antiepileptic drugs. In recent years, various animal models of epilepsy have been established to mimic different seizure types, without clear merits and demerits. Accordingly, this review provides a summary of the views mentioned above, aiming to provide a reference for animal model selection.

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“…Cl-ado and Ado inhibit the occurrence of epileptic discharge by scavenging hydroxyl radicals and their anticonvulsant effects (Yokoi et al, 1995). Fisetin reduces lipid peroxides and retains Na (+), K (+)-ATPase activities in PTE, and executes an antiepileptic role in ironinduced epileptic rat models by inhibiting oxidative stress and reduces the cognitive dysfunction related to epileptic seizures (Jharana et al, 2017). Epileptic brain fluorescent imaging revealed that apigenin relieves myeloperoxidase-mediated oxidative stress and inhibits ferroptosis (Shao et al, 2020).…”

Section: Treatment Of Epilepsy By the Regulation Of Iron Metabolism Amentioning

confidence: 99%

Iron Metabolism and Ferroptosis in Epilepsy

Chen

Zhang

et al. 2020

Front. Neurosci.

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Epilepsy is a disease characterized by recurrent, episodic, and transient central nervous system (CNS) dysfunction resulting from an excessive synchronous discharge of brain neurons. It is characterized by diverse etiology, complex pathogenesis, and difficult treatment. In addition, most epileptic patients exhibit social cognitive impairment and psychological impairment. Iron is an essential trace element for human growth and development and is also involved in a variety of redox reactions in organisms. However, abnormal iron metabolism is associated with several neurological disorders, including hemorrhagic post-stroke epilepsy and post-traumatic epilepsy (PTE). Moreover, ferroptosis is also considered a new form of regulation of cell death, which is attributed to severe lipid peroxidation caused by the production of reactive oxygen species (ROS) and iron overload found in various neurological diseases, including epilepsy. Therefore, this review summarizes the study on iron metabolism and ferroptosis in epilepsy, in order to elucidate the correlation between iron and epilepsy. It also provides a novel method for the treatment, prevention, and research of epilepsy, to control epileptic seizures and reduce nerve injury after the epileptic seizure.

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Antiepileptic effect of fisetin in iron-induced experimental model of traumatic epilepsy in rats in the light of electrophysiological, biochemical, and behavioral observations

Abstract: This study demonstrated the antiepileptic action of fisetin in iron-induced model of epileptic rats by inhibiting oxidative stress.

Cited by 47 publications

References 33 publications

Neuroprotective Effect of Fisetin Through Suppression of IL-1R/TLR Axis and Apoptosis in Pentylenetetrazole-Induced Kindling in Mice

Neuroprotective Effect of Fisetin Through Suppression of IL-1R/TLR Axis and Apoptosis in Pentylenetetrazole-Induced Kindling in Mice

Animal Models of Epilepsy: A Phenotype-oriented Review

Iron Metabolism and Ferroptosis in Epilepsy

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