title: 3-Hydroxyglutaric acid induces oxidative stress and decreases the antioxidant defenses in cerebral cortex of young rats.
abstract: Glutaryl-CoA dehydrogenase deficiency (GDD) is an inherited neurometabolic disorder biochemically characterized by tissue accumulation of glutaric, 3-hydroxyglutaric (3-OHGA) and glutaconic acids and clinically by severe neurological symptoms and cerebral atrophy whose pathophysiology is poorly known. In the present study we investigated the effect of 3-OHGA, considered the main neurotoxin in GDD, on the lipoperoxidation parameters chemiluminescence and thiobarbituric acid-reactive species (TBA-RS), and on the amount of nitric oxide metabolites in cerebral cortex of young rats. Total radical-trapping antioxidant potential (TRAP), which reflects the tissue antioxidant defenses, was also examined. We observed that 3-OHGA significantly increased chemiluminescence, TBA-RS and nitric oxide metabolites, in contrast to TRAP, which was decreased by the metabolite. The data indicate a stimulation of lipid peroxidation and free radical production, and a reduction of the tissue antioxidant defenses caused by the metabolite. In case these findings also occur in the human condition, it may be presumed that oxidative stress is involved in the brain damage observed in GDD.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal de Río Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Latini
authors.forename: Rafael
authors.initials: R
authors.lastname: Borba Rosa
authors.forename: Karina
authors.initials: K
authors.lastname: Scussiato
authors.forename: Susana
authors.initials: S
authors.lastname: Llesuy
authors.forename: Adriane
authors.initials: A
authors.lastname: Belló-Klein
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism*; D005977:Glutarates / Q000633:toxicity*; D008163:Luminescent Measurements; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: C108959:3-hydroxyglutaric acid; D000975:Antioxidants; D005977:Glutarates; D017392:Thiobarbituric Acid Reactive Substances; D009569:Nitric Oxide