title: Experimental hyperphenylalaninemia provokes oxidative stress in rat brain.
abstract: Tissue accumulation of L-phenylalanine (Phe) is the biochemical hallmark of human phenylketonuria (PKU), an inherited metabolic disorder clinically characterized by mental retardation and other neurological features. The mechanisms of brain damage observed in this disorder are poorly understood. In the present study we investigated some oxidative stress parameters in the brain of rats with experimental hyperphenylalaninemia. Chemiluminescence, total radical-trapping antioxidant potential (TRAP), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities were measured in the brain of the animals. We observed that chemiluminescence is increased and TRAP is reduced in the brain of hyperphenylalaninemic rats. Similar data were obtained in the in vitro experiments using Phe at various concentrations. CAT activity was significantly inhibited by Phe in vitro and in vivo, whereas GSH-Px activity was reduced in vivo but not in vitro and SOD activity was not altered by any treatment. The results indicate that oxidative stress may be involved in the neuropathology of PKU. However, further studies are necessary to confirm and extend our findings to the human condition and also to determine whether an antioxidant therapy may be of benefit to these patients.
authors: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Faculdade de Farmácia, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600 (Anexo) 90035-003, Porto Alegre, RS, Brazil.
authors: Martine E
authors: ME
authors: Kienzle Hagen
authors: Carolina D
authors: CD
authors: Pederzolli
authors: Angela M
authors: AM
authors: Sgaravatti
authors: Raquel
authors: R
authors: Bridi
authors: Moacir
authors: M
authors: Wajner
authors: Clóvis M D
authors: CM
authors: Wannmacher
authors: Angela T S
authors: AT
authors: Wyse
authors: Carlos S
authors: CS
authors: Dutra-Filho
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002374:Catalase / Q000032:analysis / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000032:analysis / Q000378:metabolism; D008163:Luminescent Measurements; D018384:Oxidative Stress; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology*; D010651:Phenylalanine Hydroxylase / Q000037:antagonists & inhibitors; D010661:Phenylketonurias / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000032:analysis / Q000378:metabolism
chemical_list: C012436:alpha-methylphenylalanine; D010649:Phenylalanine; D002374:Catalase; D005979:Glutathione Peroxidase; D010651:Phenylalanine Hydroxylase; D013482:Superoxide Dismutase