title: Induction of oxidative stress in rat brain by the metabolites accumulating in maple syrup urine disease.
abstract: Maple syrup urine disease (MSUD) is an inherited disorder caused by deficiency of branched-chain L-2-keto acid dehydrogenase complex activity. Affected patients present severe brain dysfunction manifested as convulsions, coma, psychomotor delay and mental retardation. However, the underlying mechanisms of these neurological findings are virtually unknown. In this study, we tested the in vitro effect of L-leucine, L-isoleucine and L-valine, the amino acids accumulating in MSUD, on the lipid peroxidation parameters chemiluminescence and thiobarbituric acid-reactive substances (TBA-RS), as well as on total radical-trapping antioxidant potential (TRAP) and total antioxidant reactivity (TAR) in cerebral cortex from 30-day-old rats. L-Leucine significantly increased chemiluminescence and TBA-RS measurements and markedly decreased TRAP and TAR values. L-Isoleucine increased chemiluminescence and decreased TRAP measurements, but TAR and TBA-RS levels were not altered by the amino acid. Finally, TRAP measurement was diminished by L-valine. The results indicate a stimulation of lipid peroxidation and a reduction of brain capacity to efficiently modulate the damage associated with an increased production of free radicals by the branched-chain amino acids (BCAAs) accumulated in MSUD. It is therefore tempting to speculate that oxidative stress may be implicated in the brain damage found in MSUD patients.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 Anexo, CEP 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Raquel
authors.initials: R
authors.lastname: Bridi
authors.forename: Janaína
authors.initials: J
authors.lastname: Araldi
authors.forename: Miriam B
authors.initials: MB
authors.lastname: Sgarbi
authors.forename: Carla G
authors.initials: CG
authors.lastname: Testa
authors.forename: Karina
authors.initials: K
authors.lastname: Durigon
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
authors.forename: Carlos Severo
authors.initials: CS
authors.lastname: Dutra-Filho
mesh_terms: D000596:Amino Acids / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals / Q000378:metabolism; D007532:Isoleucine / Q000378:metabolism / Q000494:pharmacology; D007930:Leucine / Q000378:metabolism / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008375:Maple Syrup Urine Disease / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D014633:Valine / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000596:Amino Acids; D000975:Antioxidants; D005609:Free Radicals; D007532:Isoleucine; D007930:Leucine; D014633:Valine