Homocysteine Induces Oxidative-Nitrative Stress in Heart of Rats: Prevention by Folic Acid
Homocysteine Induces Oxidative-Nitrative Stress in Heart of Rats: Prevention by Folic Acid
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DOI：
10.1007/s12012-010-9094-7
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发表时间：
2011-03-01
影响因子：
3.2
通讯作者：
Wyse, Angela T. S.
中科院分区：
文献类型：
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作者：
Kolling, Janaina;Scherer, Emilene B.;Wyse, Angela T. S.
高同型半胱氨酸血症是心血管疾病、中风和血栓形成的危险因素;然而，同型半胱氨酸触发这些功能障碍的机制尚不完全清楚。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，2 '，7'-二氯荧光素（H2 DCF）氧化，抗氧化酶超氧化物歧化酶和过氧化氢酶的活性，以及亚硝酸盐水平在年轻大鼠心脏。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大鼠从出生后第6天至第28天每天皮下注射同型半胱氨酸（0.3-0.6 μ mol/g体重）和/或叶酸（0.011 μ mol/g体重）。对照组和给药组大鼠在末次注射后1 h和/或12 h处死。结果表明，慢性同型半胱氨酸管理增加脂质过氧化和活性物质的生产，并降低酶的抗氧化防御和亚硝酸盐水平的年轻大鼠的心脏杀死1小时，但不是12小时后，最后一次注射同型半胱氨酸。叶酸同时给药可能通过其抗氧化特性防止了同型半胱氨酸的作用。我们的数据表明，氧化应激引起的慢性高同型半胱氨酸血症，一种机制，可能有助于，至少部分，高同型半胱氨酸血症患者的心血管改变的特点。如果在人类中得到证实，我们的研究结果可能表明，补充叶酸可以作为一种辅助治疗同型半胱氨酸引起的心血管改变。
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 (H2DCF) 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 mu mol/g body weight) and/or folic acid (0.011 mu mol/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.