Intracerebroventricular administration of N-acetylaspartic acid impairs antioxidant defenses and promotes protein oxidation in cerebral cortex of rats.
N-acetylaspartic acid (NAA) is the biochemical hallmark of Canavan Disease, an inherited metabolic disease caused by deficiency of aspartoacylase activity. NAA is an immediate precursor for the enzyme-mediated biosynthesis of N-acetylaspartylglutamic acid (NAAG), whose concentration is also increased in urine and cerebrospinal fluid of patients affected by CD. This neurodegenerative disorder is clinically characterized by severe mental retardation, hypotonia and macrocephaly, and generalized tonic and clonic type seizures. Considering that the mechanisms of brain damage in this disease remain not fully understood, in the present study we investigated whether intracerebroventricular administration of NAA or NAAG elicits oxidative stress in cerebral cortex of 30-day-old rats. NAA significantly reduced total radical-trapping antioxidant potential, catalase and glucose 6-phosphate dehydrogenase activities, whereas protein carbonyl content and superoxide dismutase activity were significantly enhanced. Lipid peroxidation indices and glutathione peroxidase activity were not affected by NAA. In contrast, NAAG did not alter any of the oxidative stress parameters tested. Our results indicate that intracerebroventricular administration of NAA impairs antioxidant defenses and induces oxidative damage to proteins, which could be involved in the neurotoxicity of NAA accumulation in CD patients.
Pederzolli
Carolina Didonet
CD
Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, RS, Brasil.
Rockenbach
Francieli Juliana
FJ
Zanin
Fernanda Rech
FR
Henn
Nicoli Taiana
NT
Romagna
Eline Coan
EC
Sgaravatti
Angela M
AM
Wyse
Angela T S
AT
Wannmacher
Clóvis M D
CM
Wajner
Moacir
M
de Mattos Dutra
Angela
A
Dutra-Filho
Carlos S
CS
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001224:Aspartic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D001925:Brain Damage, Chronic / Q000209:etiology / Q000378:metabolism; D017825:Canavan Disease / Q000150:complications / Q000378:metabolism*; D002374:Catalase / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004151:Dipeptides / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity; D004195:Disease Models, Animal; D005954:Glucosephosphate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D007276:Injections, Intraventricular; D015227:Lipid Peroxidation; D008297:Male; D009479:Neuropeptides / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity; D009498:Neurotoxins / Q000008:administration & dosage / Q000378:metabolism / Q000633:toxicity*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D004151:Dipeptides; D009479:Neuropeptides; D009498:Neurotoxins; C027172:isospaglumic acid; D001224:Aspartic Acid; C000179:N-acetylaspartate; D005954:Glucosephosphate Dehydrogenase; D002374:Catalase; D005979:Glutathione Peroxidase