There is an unmet need for new strategies to prevent or postpone the development of diabetic kidney disease. The pathophysiology of this condition includes as a central mechanism an imbalance between the excessive production of reactive oxygen species (ROS) and inadequate anti-oxidant defense. Reduction of ROS is therefore an interesting therapeutic target that warrants further investigation. Herein, we review the drivers of oxidative stress in diabetic kidney disease including NADPH oxidases, mitochondrial ROS production, xanthine oxidase, cytochrome P450, uncoupled eNOS and lipoxygenase. Secondly, the role of anti-oxidative mechanisms in diabetic kidney disease is discussed including the role of the kelch-like ECH-associated protein 1- nuclear factor erythroid 2-related factor 2, lipoxin, oral anti-oxidants and glutathione peroxidase-1. We will also review data supporting the concept that the beneficial renal effects of anti-diabetic drugs that target the glucagon-like peptide 1 receptor and the sodium glucose transporter 2 are, at least in part, due to their impact on oxidative stress in diabetic kidney disease. In the present article we critically evaluate both preclinical studies with cell culture experiments and animal models of diabetic kidney disease as well as covering the current findings from clinical studies addressing targeted interventions towards these pathways.

中文翻译：

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靶向糖尿病肾病中的氧化应激和抗氧化防御。

对预防或延缓糖尿病肾病发展的新策略的需求尚未得到满足。这种情况的病理生理学包括活性氧 (ROS) 的过度产生和抗氧化防御不足之间的不平衡作为中心机制。因此，减少 ROS 是一个有趣的治疗目标，值得进一步研究。在此，我们回顾了糖尿病肾病氧化应激的驱动因素，包括 NADPH 氧化酶、线粒体 ROS 产生、黄嘌呤氧化酶、细胞色素 P450、未偶联的 eNOS 和脂氧合酶。其次，讨论了抗氧化机制在糖尿病肾病中的作用，包括 kelch 样 ECH 相关蛋白 1-核因子红细胞 2 相关因子 2、脂氧素、口服抗氧化剂和谷胱甘肽过氧化物酶-1 的作用。我们还将审查支持以下概念的数据，即靶向胰高血糖素样肽 1 受体和钠葡萄糖转运蛋白 2 的抗糖尿病药物对肾脏的有益作用至少部分是由于它们对糖尿病肾脏氧化应激的影响疾病。在本文中，我们批判性地评估了细胞培养实验和糖尿病肾病动物模型的临床前研究，并涵盖了针对这些途径的针对性干预的临床研究的当前发现。