N-acetylaspartic acid impairs enzymatic antioxidant defenses and enhances hydrogen peroxide concentration in rat brain.

[canavan disease]

N-Acetylaspartic acid accumulates in Canavan Disease , a severe inherited neurometabolic disease clinically characterized by severe mental retardation , hypotonia , macrocephaly and generalized tonic and clonic type seizures . Considering that the mechanisms of brain damage in this disease remain poorly understood , in the present study we investigated the in vitro and in vivo effects of N-acetylaspartic acid on the activities of catalase , superoxide dismutase and glutathione peroxidase , as well as on hydrogen peroxide concentration in cerebral cortex of 14 -day -old rats . Catalase and glutathione peroxidase activities were significantly inhibited , while hydrogen peroxide concentration was significantly enhanced by N-acetylaspartic acid both in vitro and in vivo . In contrast , superoxide dismutase activity was not altered by N-acetylaspartic acid . Our results clearly show that N-acetylaspartic acid impairs the enzymatic antioxidant defenses in rat brain . This could be involved in the pathophysiological mechanisms responsible for the brain damage observed in patients affected by Canavan Disease .