Kienzle Hagen Martine E, Pederzolli Carolina D, Sgaravatti Angela M, Bridi Raquel, Wajner Moacir, Wannmacher Clóvis M D, Wyse Angela T S, Dutra-Filho Carlos S
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.
Biochim Biophys Acta. 2002 Apr 24;1586(3):344-52. doi: 10.1016/s0925-4439(01)00112-0.
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.
L-苯丙氨酸（Phe）在组织中的蓄积是人类苯丙酮尿症（PKU）的生化标志，苯丙酮尿症是一种遗传性代谢紊乱疾病，临床特征为智力迟钝和其他神经学特征。目前对该疾病中观察到的脑损伤机制了解甚少。在本研究中，我们调查了实验性高苯丙氨酸血症大鼠脑内的一些氧化应激参数。测量了动物脑内的化学发光、总自由基捕获抗氧化能力（TRAP）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH-Px）的活性。我们观察到，高苯丙氨酸血症大鼠脑内化学发光增加，TRAP降低。在使用不同浓度苯丙氨酸的体外实验中也获得了类似的数据。CAT活性在体外和体内均受到苯丙氨酸的显著抑制，而GSH-Px活性在体内降低，但在体外未降低，SOD活性不受任何处理的影响。结果表明，氧化应激可能参与了苯丙酮尿症的神经病理学过程。然而，需要进一步的研究来证实我们的发现，并将其扩展到人类情况，同时确定抗氧化治疗是否对这些患者有益。
