Folic acid supplementation inhibits NADPH oxidase-mediated superoxide anion production in the kidney
Folic acid supplementation inhibits NADPH oxidase-mediated superoxide anion production in the kidney
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DOI：
10.1152/ajprenal.00272.2010
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发表时间：
2011-01-01
影响因子：
4.2
通讯作者：
Karmin, O.
中科院分区：
文献类型：
--
作者：
Hwang, Sun-Young;Siow, Yaw L.;Karmin, O.
黄世英，肖玉林，吴洋，王凯。补充叶酸对肾脏NADPH氧化酶介导的超氧阴离子产生的抑制作用。[J] .中华医学杂志，2011,31(1):389 - 398。首次发表于2010年10月27日；doi: 10.1152 / ajprenal.00272.2010。高同型半胱氨酸血症是一种血液中同型半胱氨酸水平升高的疾病，是一种代谢性疾病。这是慢性肾脏疾病患者的常见临床表现，在终末期肾脏疾病患者中几乎一致发生。高同型半胱氨酸血症也是心血管疾病的一个危险因素。我们最近的研究表明，高同型半胱氨酸血症可通过诱导氧化应激导致肾损伤。氧化应激是hcy诱导组织损伤的重要机制之一。叶酸补充由于其降低hcy的作用，被认为是预防和治疗与高同型半胱氨酸血症相关的心血管疾病的一种有前途的方法。然而，它对肾脏的影响尚不清楚。本研究的目的是研究叶酸补充对高同型半胱氨酸血症期间肾内通过烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶产生hcy诱导的超氧阴离子的影响。在高蛋氨酸饮食中添加或不添加叶酸12周后，雄性Sprague-Dawley大鼠诱导高同型半胱氨酸血症。一组喂食常规食物的大鼠作为对照。高同型半胱氨酸血症大鼠肾脏中超氧阴离子和脂质过氧化物水平显著增加。NADPH氧化酶的激活是高同型半胱氨酸血症引起的肾脏氧化应激的原因。补充叶酸通过其降低hcy和不依赖hcy的作用，有效拮抗高同型半胱氨酸血症诱导的氧化应激。体外研究还表明，叶酸的活性形式5-甲基四氢叶酸（5-methyltetrahydrofolate）可以通过NADPH氧化酶有效地减少hhy诱导的超氧阴离子的产生。高同型半胱氨酸血症大鼠肾脏黄嘌呤氧化酶活性升高，超氧化物歧化酶（SOD）活性降低，这可能与肾脏超氧阴离子水平升高有关。补充叶酸可降低高同型半胱氨酸血症大鼠肾脏黄嘌呤氧化酶活性，恢复SOD活性。这些结果提示补充叶酸可能具有抗氧化应激的肾脏保护作用。
Hwang S-Y, Siow YL, Au-Yeung KK, House J, O K. Folic acid supplementation inhibits NADPH oxidase-mediated superoxide anion production in the kidney. Am J Physiol Renal Physiol 300: F189-F198, 2011. First published October 27, 2010; doi:10.1152/ajprenal.00272.2010.-Hyperhomocysteinemia, a condition of elevated blood homocysteine (Hcy) levels, is a metabolic disease. It is a common clinical finding in patients with chronic kidney diseases and occurs almost uniformly in patients with end-stage renal disease. Hyperhomocysteinemia is also a risk factor for cardiovascular disease. Our recent studies indicate that hyperhomocysteinemia can lead to renal injury by inducing oxidative stress. Oxidative stress is one of the important mechanisms contributing to Hcy-induced tissue injury. Folic acid supplementation is regarded as a promising approach for prevention and treatment of cardiovascular disease associated with hyperhomocysteinemia due to its Hcy-lowering effect. However, its effect on the kidney is not clear. The aim of this study was to examine the effect of folic acid supplementation on Hcy-induced superoxide anion production via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in the kidney during hyperhomocysteinemia. Hyperhomocysteinemia was induced in male Sprague-Dawley rats fed a high-methionine diet for 12 wk with or without folic acid supplementation. A group of rats fed a regular diet was used as control. There was a significant increase in levels of superoxide anions and lipid peroxides in kidneys isolated from hyperhomocysteinemic rats. Activation of NADPH oxidase was responsible for hyperhomocysteinemia-induced oxidative stress in the kidney. Folic acid supplementation effectively antagonized hyperhomocysteinemia-induced oxidative stress via its Hcy-lowering and Hcy-independent effect. In vitro study also showed that 5-methyltetrahydrofolate, an active form of folate, effectively reduced Hcy-induced superoxide anion production via NADPH oxidase. Xanthine oxidase activity was increased and superoxide dismutase (SOD) activity was decreased in the kidney of hyperhomocysteinemic rats, which might also contribute to an elevation of superoxide anion level in the kidney. Folic acid supplementation attenuated xanthine oxidase activity and restored SOD activity in the kidney of hyperhomocysteinemic rats. These results suggest that folic acid supplementation may offer renal protective effect against oxidative stress.