N-acetylaspartic acid impairs enzymatic antioxidant defenses and enhances hydrogen peroxide concentration in rat brain.
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.
Pederzolli
Carolina Didonet
CD
Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Mescka
Caroline Paula
CP
Magnusson
Alessandra Selinger
AS
Deckmann
Kátia Bueno
KB
de Souza Streck
Evelise
E
Sgaravatti
Angela Malysz
AM
Sgarbi
Mirian Bonaldi
MB
Wyse
Angela T S
AT
Wannmacher
Clovis M D
CM
Wajner
Moacir
M
Dutra-Filho
Carlos S
CS
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity / Q000652:urine; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D017825:Canavan Disease / Q000378:metabolism / Q000503:physiopathology; D002374:Catalase / Q000187:drug effects / Q000378:metabolism*; D004334:Drug Administration Schedule; D005260:Female; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000975:Antioxidants; D001224:Aspartic Acid; C000179:N-acetylaspartate; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase