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Hum Exp Toxicol ; 35(9): 958-65, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26500220

RESUMEN

Vigabatrin (VGB) is an antiepileptic drug thatincreases brain γ-aminobutyric acid (GABA) levels through irreversible inhibition of GABA transaminase. The aim of this study was to evaluate neurotoxicological effects of VGB measuring motor activity and genotoxic and mutagenic effects after a single and repeated administration. Male Wistar rats received saline, VGB 50, 100, or 250 mg/kg by gavage for acute and subchronic (14 days) treatments and evaluated in the rotarod task. Genotoxicity was evaluated using the alkaline version of the comet assay in samples of blood, liver, hippocampus, and brain cortex after both treatments. Mutagenicity was evaluated using the micronucleus test in bone marrow of the same animals that received subchronic treatment. The groups treated with VGB showed similar performance in rotarod compared with the saline group. Regarding the acute treatment, it was observed that only higher VGB doses induced DNA damage in blood and hippocampus. After the subchronic treatment, VGB did not show genotoxic or mutagenic effects. In brief, VGB did not impair motor activities in rats after acute and subchronic treatments. It showed a repairable genotoxic potential in the central nervous system since genotoxicity was observed in the acute treatment group.


Asunto(s)
4-Aminobutirato Transaminasa/antagonistas & inhibidores , Anticonvulsivantes/toxicidad , Daño del ADN , Micronúcleos con Defecto Cromosómico/inducido químicamente , Vigabatrin/toxicidad , Animales , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/enzimología , Corteza Cerebral/patología , Ensayo Cometa , Relación Dosis-Respuesta a Droga , Hipocampo/efectos de los fármacos , Hipocampo/enzimología , Hipocampo/patología , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/patología , Masculino , Pruebas de Micronúcleos , Actividad Motora/efectos de los fármacos , Especificidad de Órganos , Ratas Wistar , Prueba de Desempeño de Rotación con Aceleración Constante , Factores de Tiempo
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