title: Role of catalase and superoxide dismutase activities on oxidative stress in the brain of a phenylketonuria animal model and the effect of lipoic acid.
abstract: Phenylketonuria (PKU) is an inherited metabolic disorder caused by deficiency of phenylalanine hydroxylase which leads to accumulation of phenylalanine and its metabolites in tissues of patients with severe neurological involvement. Recently, many studies in animal models or patients have reported the role of oxidative stress in PKU. In the present work we studied the effect of lipoic acid against oxidative stress in rat brain provoked by an animal model of hyperphenylalaninemia (HPA), induced by repetitive injections of phenylalanine and α-methylphenylalanine (a phenylalanine hydroxylase inhibitor) for 7 days, on some oxidative stress parameters. Lipoic acid prevented alterations on catalase (CAT) and superoxide dismutase (SOD), and the oxidative damage of lipids, proteins, and DNA observed in HPA rats. In addition, lipoic acid diminished reactive species generation compared to HPA group which was positively correlated to SOD/CAT ratio. We also observed that in vitro Phe inhibited CAT activity while phenyllactic and phenylacetic acids stimulated superoxide dismutase activity. These results demonstrate the efficacy of lipoic acid to prevent oxidative stress induced by HPA model in rats. The possible benefits of lipoic acid administration to PKU patients should be considered.
authors.affiliation: Programa de Pós-Graduação em Ciências Biológicas: Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Tarsila Barros
authors.initials: TB
authors.lastname: Moraes
authors.forename: Carlos Eduardo Diaz
authors.initials: CE
authors.lastname: Jacques
authors.forename: Andrea Pereira
authors.initials: AP
authors.lastname: Rosa
authors.forename: Giovana Reche
authors.initials: GR
authors.lastname: Dalazen
authors.forename: Melaine
authors.initials: M
authors.lastname: Terra
authors.forename: Juliana Gonzalez
authors.initials: JG
authors.lastname: Coelho
authors.forename: Carlos Severo
authors.initials: CS
authors.lastname: Dutra-Filho
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D002374:Catalase / Q000378:metabolism*; D004249:DNA Damage; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010649:Phenylalanine / Q000008:administration & dosage / Q000494:pharmacology; D010651:Phenylalanine Hydroxylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010661:Phenylketonurias / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism*; D008063:Thioctic Acid / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D004791:Enzyme Inhibitors; D010649:Phenylalanine; D008063:Thioctic Acid; D002374:Catalase; D010651:Phenylalanine Hydroxylase; D013482:Superoxide Dismutase