Laboratório de Neuroproteção e Doenças Neurometabólicas, Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil; Laboratório de Erros Inatos do Metabolismo, Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil.
Laboratório de Neuroproteção e Doenças Neurometabólicas, Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil; Laboratório de Erros Inatos do Metabolismo, Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, CEP 90035-003, Porto Alegre, RS, Brazil.
Gene. 2014 Jul 15;545(1):72-9. doi: 10.1016/j.gene.2014.05.005. Epub 2014 May 2.
Homocystinuria is a neurometabolic disease caused by severe deficiency of cystathionine beta-synthase activity, resulting in severe hyperhomocysteinemia. Affected patients present several symptoms including a variable degree of motor dysfunction, being that the pathomechanism is not fully understood. In the present study we investigated the effect of chronic hyperhomocysteinemia on some parameters of oxidative stress, namely 2'7'dichlorofluorescein (DCFH) oxidation, levels of thiobarbituric acid-reactive substances (TBARS), antioxidant enzyme activities (SOD, CAT and GPx), reduced glutathione (GSH), total sulfhydryl and carbonyl content, as well as nitrite levels in soleus skeletal muscle of young rats subjected to model of severe hyperhomocysteinemia. We also evaluated the effect of creatine on biochemical alterations elicited by hyperhomocysteinemia. Wistar rats received daily subcutaneous injection of homocysteine (0.3-0.6 μmol/g body weight), and/or creatine (50mg/kg body weight) from their 6th to the 28th days age. Controls and treated rats were decapitated at 12h after the last injection. Chronic homocysteine administration increased 2'7'dichlorofluorescein (DCFH) oxidation, an index of production of reactive species and TBARS levels, an index of lipoperoxidation. Antioxidant enzyme activities, such as SOD and CAT were also increased, but GPx activity was not altered. The content of GSH, sulfhydril and carbonyl were decreased, as well as levels of nitrite. Creatine concurrent administration prevented some homocysteine effects probably by its antioxidant properties. Our data suggest that the oxidative insult elicited by chronic hyperhomocystenemia may provide insights into the mechanisms by which homocysteine exerts its effects on skeletal muscle function. Creatine prevents some alterations caused by homocysteine.
高胱氨酸尿症是一种神经代谢疾病，由胱硫醚β-合酶活性严重缺乏引起，导致严重的高同型半胱氨酸血症。受影响的患者表现出多种症状，包括不同程度的运动功能障碍，其发病机制尚未完全阐明。在本研究中，我们研究了慢性高同型半胱氨酸血症对一些氧化应激参数的影响，即 2'7'二氯荧光素（DCFH）氧化、硫代巴比妥酸反应性物质（TBARS）水平、抗氧化酶活性（SOD、CAT 和 GPx）、还原型谷胱甘肽（GSH）、总巯基和羰基含量，以及比目鱼肌骨骼肌中硝酸盐水平年轻大鼠在严重高同型半胱氨酸血症模型下。我们还评估了肌酸对高同型半胱氨酸血症引起的生化改变的影响。Wistar 大鼠从第 6 天到第 28 天每天接受皮下注射同型半胱氨酸（0.3-0.6 μmol/g 体重）和/或肌酸（50mg/kg 体重）。对照组和治疗组大鼠在最后一次注射后 12 小时断头。慢性同型半胱氨酸给药增加了 2'7'二氯荧光素（DCFH）氧化，这是活性物质产生的指标，以及 TBARS 水平，这是脂质过氧化的指标。抗氧化酶活性，如 SOD 和 CAT 也增加，但 GPx 活性没有改变。GSH、巯基和羰基含量以及硝酸盐水平降低。肌酸的同时给药可能通过其抗氧化特性预防一些同型半胱氨酸的作用。我们的数据表明，慢性高同型半胱氨酸血症引起的氧化损伤可能提供了深入了解同型半胱氨酸对骨骼肌功能影响的机制。肌酸可预防同型半胱氨酸引起的一些改变。
