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Int J Dev Neurosci ; 22(2): 67-72, 2004 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15036381

RESUMEN

Histidinemia is an inherited metabolic disorder caused by deficiency of histidase activity, which leads to tissue accumulation of histidine and its derivatives. Affected patients usually present with speech delay and mental retardation, although asymptomatic patients have been reported. Considering that the pathophysiology of the neurological dysfunction of histidinemia is not yet understood and since histidine has been considered a pro-oxidant agent, in the present study we investigated the effect of histidine and one of its derivatives, l-beta-imidazolelactic acid, at concentrations ranging from 0.1 to 10 mM, on various parameters of oxidative stress in cerebral cortex of 30-day-old Wistar rats. Chemiluminescence, total radical-trapping antioxidant potential (TRAP), thiobarbituric acid reactive substances (TBA-RS), and the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were measured in tissue homogenates in the presence of l-histidine or l-beta-imidazolelactic acid. We observed that l-histidine provoked an increase of chemiluminescence and a reduction of TRAP at concentrations of 2.5 mM and higher, while TBA-RS measurement, GSH-Px, CAT and SOD activities were not affected. Furthermore, l-beta-imidazolelactic acid provoked antioxidant effects at high concentrations (5-10 mM) as observed by the reduction of chemiluminescence, although this compound enhanced chemiluminescence at low concentrations (0.5-1 mM). These results suggest that in vitro oxidative stress is elicited by histidine but only at supraphysiological concentrations.


Asunto(s)
Errores Innatos del Metabolismo de los Aminoácidos/metabolismo , Encefalopatías Metabólicas Innatas/metabolismo , Corteza Cerebral/metabolismo , Histidina/metabolismo , Estrés Oxidativo/fisiología , Errores Innatos del Metabolismo de los Aminoácidos/fisiopatología , Animales , Encefalopatías Metabólicas Innatas/fisiopatología , Catalasa/efectos de los fármacos , Catalasa/metabolismo , Corteza Cerebral/crecimiento & desarrollo , Corteza Cerebral/fisiopatología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Radicales Libres/metabolismo , Glutatión Peroxidasa/efectos de los fármacos , Glutatión Peroxidasa/metabolismo , Histidina/farmacología , Imidazoles/farmacología , Lactatos/farmacología , Mediciones Luminiscentes , Oxidantes/farmacología , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Superóxido Dismutasa/efectos de los fármacos , Superóxido Dismutasa/metabolismo
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