Lipoic acid effects on glutamate and taurine concentrations in rat hippocampus after pilocarpine-induced seizures

Abstract

Pilocarpine-induced seizures can be mediated by increases in oxidative stress and by cerebral amino acid changes. The present research suggests that antioxidant compounds may afford some level of neuroprotection against the neurotoxicity of seizures in cellular level. The objective of the present study was to evaluate the lipoic acid (LA) effects in glutamate and taurine contents in rat hippocampus after pilocarpine-induced seizures. Wistar rats were treated intraperitoneally (i.p.) with 0.9% saline (Control), pilocarpine (400 mg/kg, Pilocarpine), LA (10 mg/kg, LA), and the association of LA (10 mg/kg) plus pilocarpine (400 mg/kg), that was injected 30 min before of administration of LA (LA plus pilocarpine). Animals were observed during 24 h. The amino acid concentrations were measured using high-performance liquid chromatograph (HPLC). In pilocarpine group, it was observed a significant increase in glutamate content (37%) and a decrease in taurine level (18%) in rat hippocampus, when compared to control group. Antioxidant pretreatment significantly reduced the glutamate level (28%) and augmented taurine content (32%) in rat hippocampus, when compared to pilocarpine group. Our findings strongly support amino acid changes in hippocampus during seizures induced by pilocarpine, and suggest that glutamate-induced brain damage plays a crucial role in pathogenic consequences of seizures, and imply that strong protective effect could be achieved using lipoic acid through the release or decrease in metabolization rate of taurine amino acid during seizures. Key words: seizures, pilocarpine, amino acids, hippocampus, glutamate, taurine.Efeitos do ácido lipóico nas concentrações de glutamato e taurina no hipocampo de ratos após convulsões induzidas por pilocarpina RESUMO As convulsões induzidas pela pilocarpina podem ser mediadas através do aumento do estresse oxidativo cerebral e das alterações na concentração dos aminoácidos. O presente estudo sugere que compostos antioxidantes podem produzir neuroproteção contra a neurotoxicidade em nível celular causada pelas convulsões. O objetivo deste estudo foi avaliar os efeitos do ácido lipóico (AL) no conteúdo de glutamato e taurina no hipocampo de ratos durante convulsões induzidas por pilocarpina. Ratos Wistar foram tratados por via intraperitoneal com solução salina 0,9% (controle), pilocarpina (400 mg/kg, pilocarpina), AL (10 mg/kg) e com a associação de AL (10 mg/kg); 30 min após com pilocarpina (400 mg/kg), que foi injetada 30 min após a administração de AL (AL + pilocarpina). Os animais foram observados durante 24 horas. As concentrações de aminoácidos foram

Oxidative Stress Associated with Neuronal Apoptosis in Experimental Models of Epilepsy

“…Several reports demonstrated that LPO levels and nitrite content in the brain of adult rats were increased after the acute phase of seizures induced by pilocarpine [ 113 – 115 ]. Agreeing with these results other works have shown in rat hippocampus a significant increase in CAT activity, glutamate content, and a decrease in taurine level [ 116 ], as well as the increase of ROS generation in CA1, CA3, and the dentate gyrus [ 117 ]. The reduction of the functions of these systems during SE produced by Pilocarpine suggests an involvement of oxidative stress in neuronal death in this experimental epilepsy model.…”

Pharmacological upregulation of GLT-1 alleviates the cognitive impairments in the animal model of temporal lobe epilepsy

“…In line with this finding, previous studies have shown that in the acute phase of epilepsy, glutamate levels in the hippocampal tissue increase significantly [48]. This increase is likely due to the increased production of glutamate from glucose in the citric acid cycle (TCA) following the severe need for neurons after continuous stimulations.…”

α-Lipoic acid alleviates pentetrazol-induced neurological deficits and behavioral dysfunction in rats with seizures via an Nrf2 pathway

“…a-Lipoic acid can respond to oxidative stressinduced apoptosis and improve the cell viability. 1,19 As studies have demonstrated, a promising candidate solution to protect the brain from neurons damage is linked with the activity of anti-oxidant enzymes.…”