Laboratório de Neuroproteção e Doenças Metabólicas, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, CEP, Porto Alegre, RS, Brazil.
Cardiovasc Toxicol. 2011 Mar;11(1):67-73. doi: 10.1007/s12012-010-9094-7.
Hyperhomocysteinemia is a risk factor for cardiovascular disease, stroke, and thrombosis; however, the mechanisms by which homocysteine triggers these dysfunctions are not fully understood. In the present study, we investigated the effect of chronic hyperhomocysteinemia on some parameters of oxidative stress, namely thiobarbituric acid reactive substances, an index of lipid peroxidation, 2',7'-dichlorofluorescein (H(2)DCF) oxidation, activities of antioxidant enzymes named superoxide dismutase and catalase, as well as nitrite levels in heart of young rats. We also evaluated the effect of folic acid on biochemical alterations elicited by hyperhomocysteinemia. Wistar rats received daily subcutaneous injection of homocysteine (0.3-0.6 μmol/g body weight) and/or folic acid (0.011 μmol/g body weight) from their 6th to the 28th day of life. Controls and treated rats were killed 1 h and/or 12 h after the last injection. Results showed that chronic homocysteine administration increases lipid peroxidation and reactive species production and decreases enzymatic antioxidant defenses and nitrite levels in the heart of young rats killed 1 h, but not 12 h after the last injection of homocysteine. Folic acid concurrent administration prevented homocysteine effects probable by its antioxidant properties. Our data indicate that oxidative stress is elicited by chronic hyperhomocystenemia, a mechanism that may contribute, at least in part, to the cardiovascular alterations characteristic of hyperhomocysteinemic patients. If confirmed in human beings, our results could propose that the supplementation of folic acid can be used as an adjuvant therapy in cardiovascular alterations caused by homocysteine.
高同型半胱氨酸血症是心血管疾病、中风和血栓形成的一个危险因素；然而，同型半胱氨酸引发这些功能障碍的机制尚未完全明了。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，即硫代巴比妥酸反应物质，脂质过氧化的一个指标，2'，7'-二氯荧光素（H（2）DCF）氧化，超氧化物歧化酶和过氧化氢酶等抗氧化酶的活性，以及年轻大鼠心脏中的硝酸盐水平。我们还评估了叶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/或叶酸（0.011 μmol/g 体重）。对照和处理大鼠在最后一次注射后 1 小时和/或 12 小时处死。结果表明，慢性同型半胱氨酸给药增加了年轻大鼠心脏中的脂质过氧化和活性物质产生，并降低了酶抗氧化防御和硝酸盐水平，这发生在最后一次注射同型半胱氨酸后 1 小时，但不是 12 小时。叶酸的同时给药可能通过其抗氧化特性预防同型半胱氨酸的作用。我们的数据表明，氧化应激是由慢性高同型半胱氨酸血症引起的，这种机制至少部分地导致了高同型半胱氨酸血症患者特有的心血管改变。如果在人类中得到证实，我们的结果可以提出，叶酸的补充可以作为同型半胱氨酸引起的心血管改变的辅助治疗。
