Oxidative stress and kidney dysfunction due to ischemia/reperfusion in rat: Attenuation by dehydroepiandrosterone
Oxidative stress and kidney dysfunction due to ischemia/reperfusion in rat: Attenuation by dehydroepiandrosterone
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DOI：
10.1046/j.1523-1755.2003.00152.x
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发表时间：
2003-09-01
影响因子：
19.6
通讯作者：
Boccuzzi, G
中科院分区：
文献类型：
--
作者：
Aragno, M;Cutrin, JC;Boccuzzi, G
背景缺血/再灌注（I/R）的发病机制涉及活性氧和氮的产生。本体内研究探讨了脱氢表雄酮（DHEA），一种具有抗氧化特性的生理类固醇，对氧化平衡和单侧I/R诱导的肾功能障碍的影响。对正常和DHEA处理的大鼠（4 mg/天x 21天，经口）进行单侧肾I/R（30分钟/6小时）。通过测定过氧化氢水平和谷胱甘肽过氧化物酶、过氧化氢酶和超氧化物歧化酶的活性来确定氧化状态。肿瘤坏死因子-α（TNF-α）和一氧化氮的生产和诱导型一氧化氮合酶（iNOS）的水平也进行了测量。羟基壬烯醛含量用于探测脂质过氧化。测定的功能参数为肌酐水平和Na/K-ATP酶活性。免疫组织化学和形态学研究也进行了。在I/R大鼠的肾脏中，明显的促氧化状态是明显的。过氧化氢和活性氮（一氧化氮和iNOS）增加，而抗氧化剂减少。氧化剂物质诱导TNF-α增加，这反过来又产生脂质过氧化过程，如通过增加的羟基壬烯醛（HNE）水平所记录的。作为最终结果，在I/R大鼠肾脏中观察到肾功能受损、水肿变性和近端回旋小管空泡化。DHEA预处理改善了所考虑的参数。I/R诱导氧化应激，从而损伤近端回旋肾小管。补充DHEA并接受I/R的大鼠具有降低的促氧化状态、氧化损伤和改善的肾功能，表明I/R介导的氧化损伤和功能障碍减弱。
Background. The pathogenesis of ischemia/reperfusion (I/R) involves generation of reactive oxygen and nitrogen species. This in vivo study investigates the effect of dehydroepiandrosterone (DHEA), a physiologic steroid with antioxidant properties, on oxidative balance and renal dysfunctions induced by monolateral I/R.Methods. Normal and DHEA-treated rats (4 mg/day x 21 days, orally) were subjected to monolateral renal I/R (30 minutes/6 hours). The oxidative state was determined by measuring hydrogen peroxide level and activities of glutathione-peroxidase, catalase, and superoxide dismutase. Tumor necrosis factor-alpha (TNF-alpha) and nitric oxide production and inducible nitric oxide synthase (iNOS) levels were also measured. Hydroxynonenal content was used to probe lipid peroxidation. Functional parameters determined were creatinine levels and Na/K-ATPase activity. Immunohistochemical and morphologic studies were also performed.Results. A markedly pro-oxidant state was evident in the kidney of rats subjected to I/R. Both hydrogen peroxide and reactive nitrogen species (nitric oxide and iNOS) increased, whereas antioxidants decreased. Oxidant species induce TNF-alpha increase, which, in turn, produces lipoperoxidative processes, as documented by the increased hydroxynonenal (HNE) level. As final result, impaired renal functionality, hydropic degeneration, and vacuolization of proximal convolute tubules were observed in kidneys of I/R rats. DHEA pretreatment improved the parameters considered.Conclusion. I/R induces oxidative stress and consequently damages the proximal convolute renal tubules. Rats supplemented with DHEA and subjected to I/R had reduced pro-oxidant state, oxidative damage, and improved renal functionality, indicating an attenuation of oxidative injury and dysfunctions mediated by I/R.