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Título :	Effect of valproic acid on levels of GABA and glutamic acid in pentylenetetrazole-damaged rat brain
Creador:	Calderón Guzmán, David
Nivel de acceso:	Open access
Palabras clave :	Anticonvulsivantes - farmacología Peso Corporal - efectos de drogas Química Encefálica - efectos de drogas Convulsivantes Acido glutámico - metabolismo Pentilenotetrazol Convulsiones - Inducidas quimicamente Covulsiones - metabolismo Acido valproico - farmacología Ácido gamma-Aminobutírico - Metabolismo Anticonvulsants - pharmacology Body Weight - drug effects Brain Chemistry - drug effects Convulsants Glutamic Acid - metabolism Pentylenetetrazole Seizures - chemically induced Seizures - metabolism Valproic Acid - pharmacology gamma-Aminobutyric Acid - metabolism
Descripción :	Epilepsy is a disorder of the central nervous system (CNS) that is characterized by the magnified response of a group of neurons to an intense stimulus due to an unbalance predominantly among stimulating and inhibiting synapses mediated by glutamic acid (Glu) and γ-amino butyric acid (GABA), respectively [1]. Several trials in patients with seizures indicate that the epileptic fits are caused by central GABAergic activity [2], although its mechanism of action is unknown. The rationale supporting the principle on which the management of antiepileptic drugs is founded includes several justifications, such as individual drug-tolerance, control of secondary effects, timing of the drug therapy, and the various biochemical mechanisms involved in the CNS [3]; these are related to the type of fit or epileptic syndrome. At present, one of the most popular antiepileptic drugs for patients with this disease is valproic acid (VPA) [4]. Even though its mechanism of action is still unclear, it has been recognized as choice treatment for epilepsy due to its broad anticonvulsive spectrum [5]. Several trials using VPA and quantitative evaluation of the electroencephalogram (EEG) spectrum [6] confirm that this drug entirely blocks the effect triggered by the repeated administration of pentylenetetrazole (PTZ). PTZ is an aromatic molecule with lipophilic qualities that has been used in several trials to cause generalized seizures in animal models [7], simulating the effects generated in human beings with epilepsy [8,9]. An additional trial using a genetic epilepsy model reports a significant increase in plasma glutamic acid levels, relating this trend with the epileptic fits [10] in individuals with epilepsy. The object of the present trial was to evaluate the variations of glutamic acid and GABA in adult rat brain treated with VPA, having previously induced experimental epilepsy with PTZ. METHODS: Male Wistar rats weighing 400 g were randomly METHODS: Male Wistar rats weighing 400 g were randomly divided into 4 groups of 6 rats each: Control (I), VPA (II), Pentylenetetrazole (III) and VPA + Pentylenetetrazole (IV). Groups II and IV were administered 150 mg/Kg of intraperitoneal VPA during 5 consecutive days, groups III and IV were administered a single dose of intraperitoneal PTZ (40 mg/Kg) thirty minutes before sacrifice on the last day of treatment. Group I was given only 0.9% NaCl through the same route of administration. Free access to food and water was provided to all groups. The animals were decapitated and their brain was sectioned into cortex, hemispheres, cerebellum, and brain stem using the standard technique [11]. The different areas were homogenized in KH 2 PO 4 buffer with a 7.4 pH and were kept at – 20°C until analyzed. The trial was authorized by the Institutional Committee on Experimental Animal Care and Utilization and by the Institution’s Research Committee. Technique for the evaluation of glutamic acid (Glu) and γ- amino butyric acid (GABA) levels. Levels of Glu and GABA were measured using the technique of Vriendt et al [12]. Samples were centrifuged at 3000 rpm and the supernatant was cleared using a 45 µm Millex HV filter for fluid and non-fluid samples after mixing it with 0.01M perchloric acid (HClO 4 ) (v/v 1:1). Subsequently, 20 µl of the supernatant were injected for chromatographic analysis using a high-pressure liquid chromatograph (HPLC) equipped with Turbochrom software version 4.1, a variable wave-length ultraviolet detector Spectra System UV1000, a Rheodyne manual injector, a GBC 4 gradient pump LC 1150, a two-channel interphase (Perkin Elmer), and a stainless steel µBondapack C-18 column (3.9 x 300 mm) (Waters Assoc.). Reagents: Merck’s reactive grade diacid potassium phosphate (KH 2 PO 4 ), methanol (HPLC grade) (Caledon Laboratories), pure standards of glutamic acid and GABA (Sigma), and deionized water using a purifying device (Waters). Chromatographic conditions: KH 2 PO 4 mobile phase 20mM. Flow rate 1.0 ml/min. Wave length 220 nm, AUFS 0.05. Statistical analysis. The approach for the statistical analysis involved comparing the levels of glutamic acid and GABA in each area among experimental groups, using one-way variance analysis (ANOVA) with previous validation of variance homogeneity by means of Bartlett’s X 2 . Probability values <0.05 were considered statistically significant [13]. RESULTS: The levels of Glu and GABA were reduced in all brain areas compared to the control group, except for the cerebellum, where Glu levels increased to some extent. On the other hand, GABA levels declined in all evaluated areas, as shown in Figure 1. Nevertheless, with the statistical test ANOVA, only the brainstem showed significant differences between the control group and the PTZ group. F brainstem = 4.67. No significant changes were noted between the VPA and the control groups
Colaborador(es) u otros Autores:	Espitia Vázquez I Barragán Mejía G Labra Ruiz N Rodríguez Pérez R Santamaria del Angel D Ayala Guerrero F Juárez Olguín H
Fecha de publicación :	2003
Tipo de publicación:	Artículo
Formato:	pdf
Fuente:	Proceedings of the Western Pharmacology Society 46():48 - 50
URI :	http://repositorio.pediatria.gob.mx:8180/handle/20.500.12103/2356
Idioma:	eng
Aparece en las colecciones:	Artículos

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