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...

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Bibliographic Details
Published in:	Metabolic brain disease Vol. 25; no. 2; pp. 251 - 259
Main Authors:	Pederzolli, Carolina Didonet, Mescka, Caroline Paula, Magnusson, Alessandra Selinger, Deckmann, Kátia Bueno, de Souza Streck, Evelise, Sgaravatti, Ângela Malysz, Sgarbi, Mirian Bonaldi, Wyse, Angela T. S., Wannmacher, Clovis M. D., Wajner, Moacir, Dutra-Filho, Carlos S.
Format:	Journal Article
Language:	English
Published:	Boston Springer US 01-06-2010 Springer Nature B.V
Subjects:	Animals Antioxidants - metabolism Aspartic Acid - analogs & derivatives Aspartic Acid - metabolism Aspartic Acid - toxicity Aspartic Acid - urine Biochemistry Biomedical and Life Sciences Biomedicine Brain - drug effects Brain - enzymology Brain - metabolism Canavan Disease - metabolism Canavan Disease - physiopathology Catalase - drug effects Catalase - metabolism Drug Administration Schedule Female Glutathione Peroxidase - drug effects Glutathione Peroxidase - metabolism Hydrogen Peroxide - metabolism Metabolic Diseases Neurology Neurosciences Oncology Original Paper Oxidative Stress - drug effects Oxidative Stress - physiology Rats Rats, Wistar Superoxide Dismutase - drug effects Superoxide Dismutase - metabolism Up-Regulation - drug effects Up-Regulation - physiology Canavan disease Glutathione peroxidase N-Acetylaspartic acid Hydrogen peroxide Catalase Rat brain
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0885-7490 1573-7365
DOI:	10.1007/s11011-010-9202-1