RESUMEN
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 percent 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 percent) and a decrease in taurine level (18 percent) in rat hippocampus, when compared to control group. Antioxidant pretreatment significantly reduced the glutamate level (28 percent) and augmented taurine content (32 percent) 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.
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 por cento (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 determinadas por HPLC. No hipocampo dos ratos do grupo pilocarpina foi observado um aumento significativo de 37 por cento na concentração de glutamato e uma diminuição de 18 por cento no nível de taurina, quando comparado ao grupo controle. O pré-tratamento com o antioxidante reduziu significativamente o nível de glutamato em 28 por cento e aumentou em 32 por cento os níveis de taurina no hipocampo dos ratos, quando comparado ao grupo pilocarpina. Nossos resultados sugerem que ocorrem alterações na concentração dos aminoácidos no hipocampo de ratos durante as convulsões induzidas por pilocarpina, e que o glutamato pode desempenhar um papel crucial na fisiopatologia das convulsões, e que o efeito protetor poderia ser alcançado com pré-tratamento com ácido lipóico, provavelmente pelo aumento da liberação ou redução da taxa de metabolização dos aminoácidos durante as convulsões.
Asunto(s)
Animales , Masculino , Ratas , Antioxidantes/farmacología , Ácido Glutámico/metabolismo , Hipocampo/efectos de los fármacos , Convulsiones/metabolismo , Taurina/metabolismo , Ácido Tióctico/farmacología , Cromatografía Líquida de Alta Presión , Hipocampo/química , Pilocarpina , Ratas Wistar , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológicoRESUMEN
In the present study we investigated the alterations on choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities in rat striatum and frontal cortex caused by pilocarpine-induced seizures. Wistar rats were treated with 0.9% saline (i.p., control group), with the association of 0.9% saline (i.p.) plus pilocarpine (400mg/kg, i.p.), 30 min before of administration of saline (pilocarpine group). After the treatments all groups were observed for 1h. The ChAT and AChE activities were measured using spectrophotometric methods and the results compared to values obtained from saline-treated animals. In pilocarpine group was observed a significantly decreases in ChAT and AChE activities in striatum and frontal cortex of adult rats, when compared to control group. Results showed that during acute phase of seizures striatal and frontal cortex ChAT and AChE activities are diminished. Our findings suggest that seizures caused cognitive dysfunction and decreases of ChAT and AChE activities that might be related, at least in part, to the neurological problems presented by epileptic patients.
Asunto(s)
Acetilcolinesterasa/metabolismo , Colina O-Acetiltransferasa/metabolismo , Cuerpo Estriado/enzimología , Lóbulo Frontal/enzimología , Pilocarpina , Convulsiones/enzimología , Animales , Masculino , Ratas , Ratas Wistar , Convulsiones/inducido químicamenteRESUMEN
This work was designed to study the influence of drugs during seizures and status epilepticus (SE) induced by pilocarpine and mortality in adult rats. Glutamate (10 and 20 mg/kg), N-methyl-d-aspartate (NMDA, 5 and 10 mg/kg), ketamine (1.5 and 2.0 mg/kg), gabapentin (200 and 250 mg/kg), phenobarbital (50 and 100 mg/kg) and vigabatrin (250 and 500 mg/kg) were administered intraperitoneally, 30 min prior to pilocarpine (400 mg/kg, i.p.). The animals were observed (24 h) to determine: number of peripheral cholinergic signs, tremors, stereotyped movements, seizures, SE, latency to first seizure and number of deaths after pilocarpine treatment. NMDA and glutamate had pro-convulsive effects in both doses tested. Smaller and higher doses of these drugs no protected and increased pilocarpine-induced seizures and/or mortality. Gabapentin, vigabatrin, phenobarbital and ketamine protected against seizures and increased the latency to first seizure. Thus, these results suggest that caution should be taken in the selection of pharmacotherapy and dosages for patients with seizures and SE because of the possibility of facility the convulsive process toxicity, SE and the mortality of adult animals in this seizures model that is similar temporal lobo epilepsy in humans.
Asunto(s)
Anticonvulsivantes/farmacología , Receptores de GABA/efectos de los fármacos , Receptores de Neurotransmisores/efectos de los fármacos , Convulsiones/fisiopatología , Estado Epiléptico/fisiopatología , Aminas/farmacología , Animales , Ácidos Ciclohexanocarboxílicos/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Gabapentina , Ácido Glutámico/farmacología , Glutamina/metabolismo , Ketamina/farmacología , Masculino , Agonistas Muscarínicos/toxicidad , N-Metilaspartato/farmacología , Fenobarbital/farmacología , Pilocarpina/toxicidad , Ratas , Ratas Wistar , Convulsiones/inducido químicamente , Estado Epiléptico/inducido químicamente , Vigabatrin/farmacología , Ácido gamma-Aminobutírico/metabolismo , Ácido gamma-Aminobutírico/farmacologíaRESUMEN
Experimental manipulations suggest that in vivo administration of exogenous antioxidants agents decreases the concentration of free radical in the brain. Neurochemical studies have proposed a role for catalase in brain mechanisms responsible by development to status epilepticus (SE) induced by pilocarpine. The present study was aimed at was investigating the changes in catalase activities after pilocarpine-induced SE. Animals were treated with vitamin E (VIT E) 200 mg/kg (intraperitoneally (i.p.)) and, 30 min later, they received pilocarpine hydrochloride, 400 mg/kg, subcutaneous (s.c.) (P400). Other three groups received VIT E (200 mg/kg, i.p.), pilocarpine (400 mg/kg, s.c.) or 0.9% NaCl (control) alone. Animals were closely observed for behavioral changes, tremors, stereotyped movements, seizures, SE and death, for 24 h following the pilocarpine injection. The brains were dissected after decapitation. The results have shown that pilocarpine administration and resulting SE produced a significant increase in hippocampal catalase activity of (88%). In the group pre-treated which VIT E in hippocampal catalase activity was increase of 67% and 214% when compared with P400 and control group, respectively. Our results demonstrated a direct evidence of an increase in the activity of the hippocampal catalase of rat adults during seizure activity and after the pre-treated which VIT E that could be responsible by regulation of free radical levels during the establishment of SE.