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

Abstract

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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