Programa de Pós-Graduação em Ciências Biológicas:Bioquímica da Universidade Federal do Rio Grande do Sul (UFRGS), Ramiro Barcelos 2700, Porto Alegre, RS, 90035-000, Brazil.
Mol Genet Metab. 2011 Sep-Oct;104(1-2):112-7. doi: 10.1016/j.ymgme.2011.06.013. Epub 2011 Jun 24.
Homocystinuria is an inherited disorder biochemically characterized by high urinary excretion of homocystine and increased levels of homocysteine (Hcy) and methionine in biological fluids. Affected patients usually have a variety of clinical and pathologic manifestations. Previous experimental data have shown a relationship between Hcy and oxidative stress, although very little was reported on this process in patients with homocystinuria. Therefore, in the present study we evaluated parameters of oxidative stress, namely carbonyl formation, malondialdehyde (MDA) levels, sulfhydryl content and total antioxidant status (TAS) in patients with homocystinuria at diagnosis and under treatment with a protein restricted diet supplemented by pyridoxine, folate, betaine, and vitamin B(12). We also correlated plasma Hcy and methionine concentrations with the oxidative stress parameters examined. We found a significant increase of MDA levels and carbonyl formation, as well as a reduction of sulfhydryl groups and TAS in plasma of homocystinuric patients at diagnosis relatively to healthy individuals (controls). We also verified that Hcy levels were negatively correlated with sulfhydryl content and positively with MDA levels. Furthermore, patients under treatment presented a significant reduction of the content of MDA, Hcy and methionine concentrations relatively to patients at diagnosis. Taken together, the present data indicate that lipid and protein oxidative damages are increased and the antioxidant defenses diminished in plasma of homocystinuric patients, probably due to increased reactive species elicited by Hcy. It is therefore presumed that oxidative stress participates at least in part in the pathogenesis of homocystinuria.
高胱氨酸尿症是一种遗传性疾病，其生化特征为尿液中同型半胱氨酸排泄增加，生物体液中同型半胱氨酸（Hcy）和蛋氨酸水平升高。受影响的患者通常具有多种临床和病理表现。先前的实验数据表明 Hcy 与氧化应激之间存在关系，尽管在高胱氨酸尿症患者中对此过程的报道很少。因此，在本研究中，我们在诊断时和接受限制蛋白质饮食补充吡哆醇、叶酸、甜菜碱和维生素 B12 治疗的高胱氨酸尿症患者中评估了氧化应激参数，即羰基形成、丙二醛（MDA）水平、巯基含量和总抗氧化状态（TAS）。我们还将血浆 Hcy 和蛋氨酸浓度与检查的氧化应激参数相关联。我们发现高胱氨酸尿症患者在诊断时的 MDA 水平和羰基形成明显增加，以及血浆中巯基含量和 TAS 减少，相对健康个体（对照组）而言。我们还证实 Hcy 水平与巯基含量呈负相关，与 MDA 水平呈正相关。此外，与诊断时的患者相比，接受治疗的患者的 MDA、Hcy 和蛋氨酸浓度显著降低。综上所述，这些数据表明，高胱氨酸尿症患者血浆中的脂质和蛋白质氧化损伤增加，抗氧化防御能力降低，这可能是由于 Hcy 引起的活性物质增加所致。因此，可以推测氧化应激至少部分参与了高胱氨酸尿症的发病机制。
