Bridi Raquel, Araldi Janaína, Sgarbi Miriam B, Testa Carla G, Durigon Karina, Wajner Moacir, Dutra-Filho Carlos Severo
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.
Int J Dev Neurosci. 2003 Oct;21(6):327-32. doi: 10.1016/s0736-5748(03)00074-1.
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.
枫糖尿症（MSUD）是一种由支链L-2-酮酸脱氢酶复合物活性缺乏引起的遗传性疾病。受影响的患者表现出严重的脑功能障碍，表现为惊厥、昏迷、精神运动发育迟缓及智力低下。然而，这些神经学表现的潜在机制几乎尚不清楚。在本研究中，我们检测了MSUD中蓄积的氨基酸L-亮氨酸、L-异亮氨酸和L-缬氨酸对30日龄大鼠大脑皮质脂质过氧化参数化学发光和硫代巴比妥酸反应性物质（TBA-RS），以及对总自由基捕获抗氧化能力（TRAP）和总抗氧化反应性（TAR）的体外作用。L-亮氨酸显著增加化学发光和TBA-RS的测量值，并显著降低TRAP和TAR值。L-异亮氨酸增加化学发光并降低TRAP测量值，但该氨基酸未改变TAR和TBA-RS水平。最后，L-缬氨酸降低了TRAP测量值。结果表明脂质过氧化受到刺激，且大脑有效调节与MSUD中蓄积的支链氨基酸（BCAAs）自由基生成增加相关损伤的能力降低。因此，很容易推测氧化应激可能与MSUD患者的脑损伤有关。
