title: N-acetylaspartic acid impairs enzymatic antioxidant defenses and enhances hydrogen peroxide concentration in rat brain.
abstract: 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.
authors.affiliation: Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Carolina Didonet
authors.initials: CD
authors.lastname: Pederzolli
authors.forename: Caroline Paula
authors.initials: CP
authors.lastname: Mescka
authors.forename: Alessandra Selinger
authors.initials: AS
authors.lastname: Magnusson
authors.forename: Kátia Bueno
authors.initials: KB
authors.lastname: Deckmann
authors.forename: Evelise
authors.initials: E
authors.lastname: de Souza Streck
authors.forename: Angela Malysz
authors.initials: AM
authors.lastname: Sgaravatti
authors.forename: Mirian Bonaldi
authors.initials: MB
authors.lastname: Sgarbi
authors.forename: Angela T S
authors.initials: AT
authors.lastname: Wyse
authors.forename: Clovis M D
authors.initials: CM
authors.lastname: Wannmacher
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
authors.forename: Carlos S
authors.initials: CS
authors.lastname: Dutra-Filho
mesh_terms: 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
chemical_list: D000975:Antioxidants; D001224:Aspartic Acid; C000179:N-acetylaspartate; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase