Ratliff Brian B, Abdulmahdi Wasan, Pawar Rahul, Wolin Michael S
1 Department of Medicine, Renal Research Institute , New York Medical College, Valhalla, New York.
2 Department of Physiology, Renal Research Institute , New York Medical College, Valhalla, New York.
Antioxid Redox Signal. 2016 Jul 20;25(3):119-46. doi: 10.1089/ars.2016.6665. Epub 2016 Apr 26.
A common link between all forms of acute and chronic kidney injuries, regardless of species, is enhanced generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) during injury/disease progression. While low levels of ROS and RNS are required for prosurvival signaling, cell proliferation and growth, and vasoreactivity regulation, an imbalance of ROS and RNS generation and elimination leads to inflammation, cell death, tissue damage, and disease/injury progression.
Many aspects of renal oxidative stress still require investigation, including clarification of the mechanisms which prompt ROS/RNS generation and subsequent renal damage. However, we currently have a basic understanding of the major features of oxidative stress pathology and its link to kidney injury/disease, which this review summarizes.
The review summarizes the critical sources of oxidative stress in the kidney during injury/disease, including generation of ROS and RNS from mitochondria, NADPH oxidase, and inducible nitric oxide synthase. The review next summarizes the renal antioxidant systems that protect against oxidative stress, including superoxide dismutase and catalase, the glutathione and thioredoxin systems, and others. Next, we describe how oxidative stress affects kidney function and promotes damage in every nephron segment, including the renal vessels, glomeruli, and tubules.
Despite the limited success associated with the application of antioxidants for treatment of kidney injury/disease thus far, preventing the generation and accumulation of ROS and RNS provides an ideal target for potential therapeutic treatments. The review discusses the shortcomings of antioxidant treatments previously used and the potential promise of new ones. Antioxid. Redox Signal. 25, 119-146.
无论物种如何，所有形式的急性和慢性肾损伤之间的一个共同联系是在损伤/疾病进展过程中活性氧（ROS）和活性氮（RNS）的生成增加。虽然低水平的ROS和RNS对于促生存信号传导、细胞增殖和生长以及血管反应性调节是必需的，但ROS和RNS生成与消除的失衡会导致炎症、细胞死亡、组织损伤以及疾病/损伤进展。
肾脏氧化应激的许多方面仍需研究，包括促使ROS/RNS生成及随后肾脏损伤的机制的阐明。然而，我们目前对氧化应激病理学的主要特征及其与肾损伤/疾病的联系有了基本了解，本综述对此进行了总结。
本综述总结了损伤/疾病期间肾脏氧化应激的关键来源，包括线粒体、NADPH氧化酶和诱导型一氧化氮合酶产生的ROS和RNS。接下来，综述总结了抵御氧化应激的肾脏抗氧化系统，包括超氧化物歧化酶和过氧化氢酶、谷胱甘肽和硫氧还蛋白系统等。然后，我们描述了氧化应激如何影响肾功能并促进每个肾单位节段（包括肾血管、肾小球和肾小管）的损伤。
尽管迄今为止抗氧化剂在治疗肾损伤/疾病方面取得的成功有限，但防止ROS和RNS的生成和积累为潜在的治疗提供了理想靶点。本综述讨论了先前使用的抗氧化剂治疗的缺点以及新抗氧化剂的潜在前景。《抗氧化与氧化还原信号》25卷，第119 - 146页。
