Melatonin Inhibits Iron‐Induced Epileptic Discharges in Rats by Suppressing Peroxidation

Kabuto, Hideaki; Yokoi, Isao; Ogawa, Norio

doi:10.1111/j.1528-1157.1998.tb01367.x

Cited by 123 publications

(65 citation statements)

References 33 publications

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“…The signal transduction regulatory properties of tocotrienols, however, are yet unknown. ROS 1 represent a major contributor to brain damage in disorders such as epilepsy (11,12), head trauma (13), and ischemia-reperfusion (14 -16). Oxidative damage is also implicated in neurodegenerative diseases such as Huntington's (17), Alzheimer's (18), and Parkinson's.…”

mentioning

confidence: 99%

Molecular Basis of Vitamin E Action

Sen

Khanna

Roy

et al. 2000

Journal of Biological Chemistry

279

113

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HT4 hippocampal neuronal cells were studied to compare the efficacy of tocopherols and tocotrienol to protect against glutamate-induced death. Tocotrienols were more effective than ␣-tocopherol in preventing glutamate-induced death. Uptake of tocotrienols from the culture medium was more efficient compared with that of ␣-tocopherol. Vitamin E molecules have potent antioxidant properties. Results show that at low concentrations, tocotrienols may have protected cells by an antioxidant-independent mechanism. Examination of signal transduction pathways revealed that protein tyrosine phosphorylation processes played a central role in the execution of death. Activation of pp60 c-Src kinase and phosphorylation of ERK were observed in response to glutamate treatment. Nanomolar amounts of ␣-tocotrienol, but not ␣-tocopherol, blocked glutamate-induced death by suppressing glutamate-induced early activation of c-Src kinase. Overexpression of kinase-active cSrc sensitized cells to glutamate-induced death. Tocotrienol treatment prevented death of Src-overexpressing cells treated with glutamate. ␣-Tocotrienol did not influence activity of recombinant c-Src kinase suggesting that its mechanism of action may include regulation of SH domains. This study provides first evidence describing the molecular basis of tocotrienol action. At a concentration 4 -10-fold lower than levels detected in plasma of supplemented humans, tocotrienol regulated unique signal transduction processes that were not sensitive to comparable concentrations of tocopherol.

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mentioning

confidence: 99%

Molecular Basis of Vitamin E Action

Sen

Khanna

Roy

et al. 2000

Journal of Biological Chemistry

279

113

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“…Kainate-induced convulsions were reduced in rats given intraperitoneal melatonin (15). The occurrence of iron-induced epileptic EEG discharges was reduced in rats given intraperitoneal melatonin (16). Dose-dependent anticonvulsive effects of melatonin were observed in convulsions induced by intracerebroventricular administration of quinolinic acid, kainate, glutamate, NMDA, and pentylenetetrazole (17).…”

Section: Introductionmentioning

confidence: 81%

Melatonin Does Not Provide Protection Against Hyperbaric Oxygen (HBO) Induced Seizures

Swiergosz¹,

Keyser²,

Koller³

2004

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“…Previous studies described a model of limbic seizures followed by brain damage produced by systemic injection of a high dose of pilocarpine (400 mg/kg) in rats 5,23 . The evidence included temporal correlation among free radical generation, development of seizures and neuroprotective effects of antioxidant drugs against neuronal damage caused by seizures 24 .…”

Section: Discussionmentioning

confidence: 99%

Inhibitory action of antioxidants (ascorbic acid or α-tocopherol) on seizures and brain damage induced by pilocarpine in rats

Tomé

Ferreira

Freitas

2010

Arq. Neuro-Psiquiatr.

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Temporal lobe epilepsy is the most common form of epilepsy in humans. Oxidative stress is a mechanism of cell death induced by seizures. Antioxidant compounds have neuroprotective effects due to their ability to inhibit free radical production. The objectives of this work were to comparatively study the inhibitory action of antioxidants (ascorbic acid or α-tocopherol) on behavioral changes and brain damage induced by high doses of pilocarpine, aiming to further clarify the mechanism of action of these antioxidant compounds. In order to determinate neuroprotective effects, we studied the effects of ascorbic acid (250 or 500 mg/ kg, i.p.) and α-tocopherol (200 or 400 mg/kg, i.p.) on the behavior and brain lesions observed after seizures induced by pilocarpine (400 mg/kg, i.p., P400 model) in rats. Ascorbic acid or α-tocopherol injections prior to pilocarpine suppressed behavioral seizure episodes. These findings suggested that free radicals can be produced during brain damage induced by seizures. In the P400 model, ascorbic acid and α-tocopherol significantly decreased cerebral damage percentage. Antioxidant compounds can exert neuroprotective effects associated with inhibition of free radical production. These results highlighted the promising therapeutic potential of ascorbic acid and α-tocopherol in treatments for neurodegenerative diseases. Key words: seizures, status epilepticus, pilocarpine, ascorbic acid, α-tocopherol.Ação inibitória de antioxidantes (ácido ascórbico e α-tocoferol) nas convulsões e dano cerebral em ratos induzidos pela pilocarpina resumo A epilepsia de lobo temporal é a mais comum forma de epilepsia em humanos. O estresse oxidativo é um dos mecanismos de morte celular induzida pelas crises convulsivas. Os compostos antioxidantes apresentam efeitos neuroprotetores devido à sua capacidade de inibir a produção de radicais livres. Os objetivos do presente trabalho foram estudar de forma comparativa a ação inibitória de antioxidantes (ácido ascórbico e α-tocoferol) sobre as alterações comportamentais e histopatológicas no hipocampo de ratos após convulsões induzidas pela pilocarpina. A fim de determinar os efeitos neuroprotetores destas drogas, o presente trabalho estudou os efeitos do ácido ascórbico (250 ou 500 mg/kg, i.p.) e do α-tocoferol (200 ou 400 mg/kg, i.p.) sobre o comportamento e as lesões cerebrais observados após convulsões induzidas pela pilocarpina (400 mg/kg, i.p., P400), em ratos. As injeções de ácido ascórbico ou α-tocoferol antes da administração de pilocarpina reduzem o número de animais que convulsionam. Estes achados sugerem que os radicais livres podem induzir o desenvolvimento de lesão cerebral durante as crises epilépticas. No modelo P400, o ácido ascórbico e o α-tocoferol, diminuem significativamente os danos cerebrais. Os compostos antioxidantes podem exercer efeitos neuroprotetores, e esses resultados podem estar associados à inibição da produção de radicais livres. Estes resultados sugerem um promissor potencial terapêutico tanto para o ácido ascórbico quanto...

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Melatonin Inhibits Iron‐Induced Epileptic Discharges in Rats by Suppressing Peroxidation

Cited by 123 publications

References 33 publications

Molecular Basis of Vitamin E Action

Molecular Basis of Vitamin E Action

Melatonin Does Not Provide Protection Against Hyperbaric Oxygen (HBO) Induced Seizures

Inhibitory action of antioxidants (ascorbic acid or α-tocopherol) on seizures and brain damage induced by pilocarpine in rats

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