Oxidative stress in chronic renal allograft nephropathy in rats:: Effects of long-term treatment with carvedilol, BM 91.0228, or alpha-tocopherol
Oxidative stress in chronic renal allograft nephropathy in rats:: Effects of long-term treatment with carvedilol, BM 91.0228, or alpha-tocopherol
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DOI：
10.1097/00005344-200309000-00017
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发表时间：
2003-09-01
影响因子：
3
通讯作者：
Braun, C
中科院分区：
文献类型：
--
作者：
Göttmann, U;Oltersdorf, J;Braun, C
肾移植后氧化应激显著增加，并可能参与慢性移植肾肾病的发生和/或进展。在本研究中，我们试图评估抗氧化治疗对肾移植受者的肾脏保护潜力。实验在慢性移植肾肾病的Fisher - Lewis大鼠模型中进行，以同基因移植的Lewis大鼠作为对照。同种异体移植大鼠分别口服卡维地洛（一种具有抗氧化特性的抗高血压药物，25mg/kg/d）、其纯抗氧化衍生物BM 91.0228（5mg/kg/d）、α - 生育酚（100mg/kg/d）、普萘洛尔/多沙唑嗪组合（10/5mg/kg/d）或赋形剂，持续24周。在研究结束时，评估移植动物的氧化状态和抗氧化治疗的影响。慢性移植肾肾病的特征是氧化应激标志物显著增加（同种异体移植肾中血浆和肾脏丙二醛水平升高，还原型谷胱甘肽和生育酚水平降低）。卡维地洛、BM 91.0228和生育酚治疗显著改善了同种异体移植肾受者的抗氧化状态。此外，卡维地洛降低了同种异体移植大鼠的升高的血压。然而，这些药物对肾脏的功能和形态学改变均无有益影响。因此，我们的数据表明，尽管抗氧化状态有所改善，但长期使用抗氧化剂卡维地洛、BM 91.0228或α - 生育酚治疗并不能预防慢性移植肾病的发生。
Oxidative stress is markedly increased after kidney transplantation and may participate in the development and/or progression of chronic renal allograft nephropathy. In the present study we sought to assess the nephroprotective potential of antioxidative treatment in renal allograft recipients. Experiments were performed in the Fisher-Lewis rat model of chronic renal allograft nephropathy, with isografted Lewis rats serving as controls. Allografted rats were orally treated with carvedilol, an antihypertensive drug with antioxidative properties (25 mg/kg/d), its purely antioxidative derivative BM 91.0228 (5 mg/kg/d), alpha-tocopherol (100 mg/kg/d), a combination of propranolol/doxazosine (10/5 mg/kg/d), or vehicle for 24 weeks. At the end of the study, oxidative status and influence of antioxidative treatment were assessed in transplanted animals. Chronic allograft nephropathy was characterized by a marked increase of markers for oxidative stress (increased plasma and kidney levels of malondialdehyde, reduced glutathione, and tocopherol levels in renal allografts). Treatment with carvedilol, BM 91.0228, and tocopherol significantly improved antioxidative status of allograft kidney recipients. In addition, carvedilol reduced elevated blood pressure in allografted rats. However none of the drugs had a beneficial influence on functional and morphologic renal changes. Our data thus demonstrate that long-term treatment with the antioxidants carvedilol, BM 91.0228, or alpha-tocopherol does not prevent development of chronic transplant nephropathy, despite an improvement of antioxidative status.