Long-term monotherapy treatment with vitamin E reduces oxidative stress, but not seizure frequency in rats submitted to the pilocarpine model of epilepsy

Pansani, Aline Priscila; Cysneiros, Roberta Monterazzo; Colugnati, Diego Basile; Janjoppi, Luciana; Ferrari, Danuza; Lima, Edson Alves de; Ghazale, Poliana Peres; Sinigaglia‐Coimbra, Rita; Scorza, Fúlvio A.

doi:10.1016/j.yebeh.2018.09.027

Cited by 8 publications

(4 citation statements)

References 55 publications

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“…This was confirmed in a recent study, which demonstrated that long-term treatment with 60 IU/kg/day of vitamin E prevented oxidative damage in the hippocampus and increased hilar parvalbumin expression in rats with epilepsy without a reduction in seizure frequency [53].…”

Section: Neuroprotective and Antiepileptogenic Role Of Ros Inhibitionsupporting

confidence: 69%

Reactive oxygen species in status epilepticus

Shekh‐Ahmad

Kovač

Abramov

et al. 2019

Epilepsy & Behavior

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There has been growing evidence for a critical role of oxidative stress in neurodegenerative disease, providing novel targets for disease modifying treatments. Although antioxidants have been suggested and tried in the treatment of epilepsy, it is only recently that the pivotal role of oxidative stress in the pathophysiology of status epilepticus has been recognised. Although conventionally thought to be generated by mitochondria, reactive oxygen species during status epilepticus and prolonged seizure are generated activity mainly by NADPH oxidase (stimulated by NMDA receptor activation). Excessive production of reactive oxygen species results in lipid peroxidation, DNA damage, enzyme inhibition and mitochondrial damage, culminating in neuronal death. Antioxidant therapy has been hampered by poor CNS penetration and rapid consumption by antioxidants. However, alternative approaches such as inhibiting NADPH oxidase or increasing endogenous antioxidant defences through activation of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) could avoid these problems. Small molecules that increase Nrf2 activation have proven to be not only effective neuroprotectants following status epilepticus, but also potently antiepileptogenic. There are a range of Nrf2 activators that are in clinical trial for other indications, suggesting that repurposing of these therapies could provide a rapid translation of these for the treatment of status epilepticus. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures.

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Section: Neuroprotective and Antiepileptogenic Role Of Ros Inhibitionsupporting

confidence: 69%

Reactive oxygen species in status epilepticus

Shekh‐Ahmad

Kovač

Abramov

et al. 2019

Epilepsy & Behavior

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“…There have been reports of the successful use of antioxidants, such as α‐tocopherol/vitamin E in status epilepticus, reducing neuronal injury and inflammation. 34 , 35 , 36 However, many of the studies of antioxidants have mixed results and are confounded by timing of administration, blood‐brain barrier penetration, doses used, and coadministration with other compounds. 37 In addition, the translational potential of many of the studies is low, as the antioxidant is given prior to the induction of status epilepticus.…”

Section: Neuroprotective Role Of Antioxidant Strategiesmentioning

confidence: 99%

“…The observations that free radical generation occurs during status epilepticus and that there are key roles of peroxynitrite and ROS in mitochondrial dysfunction and neuronal death (Figure 1) lead to the supposition that antioxidants should have a neuroprotective effect. There have been reports of the successful use of antioxidants, such as α‐tocopherol/vitamin E in status epilepticus, reducing neuronal injury and inflammation 34–36 . However, many of the studies of antioxidants have mixed results and are confounded by timing of administration, blood‐brain barrier penetration, doses used, and coadministration with other compounds 37 .…”

Section: Neuroprotective Role Of Antioxidant Strategiesmentioning

confidence: 99%

Reactive oxygen species in status epilepticus

Walker

2023

Epilepsia Open

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It has long been recognized that status epilepticus can cause considerable neuronal damage, and this has become one of its defining features. The mechanisms underlying this damage are less clear. Excessive activation of NMDA receptors results in large rises in internal calcium, which eventually lead to neuronal death. Between NMDA receptor activation and neuronal death are a number of intermediary steps, key among which is the generation of free radicals and reactive oxygen and nitrogen species. Although it has long been thought that mitochondria are the primary source for reactive oxygen species, more recent evidence has pointed to a prominent role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, an enzyme localized in cell membranes. There is burgeoning in vivo and in vitro evidence that therapies that target the production or removal of reactive oxygen species are not only effective neuroprotectants following status epilepticus, but also potently antiepileptogenic. Moreover, combining therapies targeted at inhibiting NADPH oxidase and at increasing endogenous antioxidants seems to offer the greatest benefits.

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“…In some of these studies, the anticonvulsant action of vitamin E was accompanied by a lowering of brain lipid peroxidation and nitrite content, which may result in increased cytoprotection and neuronal survival as ultimate prevention mechanisms against hippocampal damage [23]. Other recent studies on pilocarpine-induced epilepsy model have confirmed the protection against oxidant stress of the brain, but not the anticonvulsant activity [154], pointing to different levels of outcome for different dosages of the vitamin and epileptogenic models.…”

Section: Vitamin E: An Effective Fighter In Counteracting Oxidative S...mentioning

confidence: 99%