Effects of tempol and redox-cycling nitroxides in models of oxidative stress.
Effects of tempol and redox-cycling nitroxides in models of oxidative stress.
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DOI：
10.1016/j.pharmthera.2010.01.003
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发表时间：
2010-05
影响因子：
13.5
通讯作者：
Wilcox, Christopher S.
中科院分区：
文献类型：
--
作者：
Wilcox, Christopher S.
Tempol 是一种氧化还原循环氮氧化物，可促进许多活性氧 (ROS) 的代谢并提高一氧化氮的生物利用度。它已在氧化应激动物模型中得到广泛研究。 Tempol 已被证明可以保护线粒体免受氧化损伤并改善组织氧合作用。 Tempol 改善了糖尿病模型中的胰岛素反应性，改善了脂肪喂养的代谢综合征模型中的血脂异常、减少了体重增加并预防了舒张功能障碍和心力衰竭。 Tempol 保护许多器官，包括心脏和大脑，免受缺血/再灌注损伤。 Tempol 可预防盐和盐皮质激素过量模型中的足细胞损伤、肾小球硬化、蛋白尿和肾功能进行性丧失。它可以减少缺血或创伤后的大脑或脊髓损伤，并发挥脊髓镇痛作用。 Tempol 提高了几种休克模型的生存率。它保护正常细胞免受辐射，同时保持肿瘤细胞的辐射敏感性。它在肿瘤细胞中的矛盾的促氧化作用导致自发肿瘤形成的减少。 Tempol 对某些神经退行性疾病模型有效。因此，tempol 可以有效预防氧化应激和炎症的多种不良后果，这些不良后果是辐射损伤和许多与衰老相关的疾病的基础。事实上，从出生起就给予tempol可以延长正常小鼠的寿命。然而，目前tempol仅在人类受试者中用作预防辐射引起的脱发的局部制剂。
Tempol is a redox cycling nitroxide that promotes the metabolism of many reactive oxygen species (ROS) and improves nitric oxide bioavailability. It has been studied extensively in animal models of oxidative stress. Tempol has been shown to preserve mitochondria against oxidative damage and improve tissue oxygenation. Tempol improved insulin responsiveness in models of diabetes mellitus and improved the dyslipidemia, reduced the weight gain and prevented diastolic dysfunction and heart failure in fat-fed models of the metabolic syndrome. Tempol protected many organs, including the heart and brain, from ischemia/reperfusion damage. Tempol prevented podocyte damage, glomerulosclerosis, proteinuria and progressive loss of renal function in models of salt and mineralocorticosteroid excess. It reduced brain or spinal cord damage after ischemia or trauma and exerted a spinal analgesic action. Tempol improved survival in several models of shock. It protected normal cells from radiation while maintaining radiation sensitivity of tumor cells. Its paradoxical pro-oxidant action in tumor cells accounted for a reduction in spontaneous tumor formation. Tempol was effective in some models of neurodegeneration. Thus, tempol has been effective in preventing several of the adverse consequences of oxidative stress and inflammation that underlie radiation damage and many of the diseases associated with aging. Indeed, tempol given from birth prolonged the life span of normal mice. However, presently tempol has been used only in human subjects as a topical agent to prevent radiation-induced alopecia.
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