Guerrero-Hue Melania, Farre-Alins Victor, Palomino-Antolin Alejandra, Parada Esther, Rubio-Navarro Alfonso, Egido Jesus, Egea Javier, Moreno Juan A
Renal, Vascular and Diabetes Research Laboratory, Instituto de Investigacion Sanitaria -Fundacion Jimenez Diaz, Autonoma University, 28040 Madrid. Spain.
Instituto de Investigacion Sanitaria-Hospital Universitario de la Princesa, Madrid, Spain; Department of Pharmacology, Instituto Teofilo Hernando, Facultad de Medicina, UAM, Madrid. Spain.
Curr Med Chem. 2017;24(33):3583-3605. doi: 10.2174/0929867324666170511120814.
Renal disease is a serious health problem, with increasing incidence and prevalence. Oxidative stress and inflammation play a key role in the pathogenesis and progression of renal disease. Therefore, therapeutic approaches to decrease oxidative stress should be of interest.
This review aims to provide a comprehensive and updated overview of the protective mechanisms mediated by Nrf2 (nuclear factor erythroid 2-related factor 2), a description of novel compounds that target Nrf2, its effectiveness to prevent renal disease and the on-going clinical trials for this pathological condition.
We undertook a structured search of bibliographic databases for peer-reviewed research in literature about Nrf2 activators and renal disease.
The transcription factor Nrf2 is an emerging regulator of cellular resistance to oxidants and inflammation. Nrf2 controls the basal and induced expression of a couple of cytoprotective and antiinflammatory genes that regulate the physiological and pathophysiological outcomes of oxidant exposure. We have analyzed numerous findings showing that Nrf2 induction protects against oxidative stress and modulates inflammation in acute kidney injury and chronic kidney disease progression. However, few clinical trials have been performed in humans. Recent studies suggested that renoprotective effects of Nrf2 activation are observed at low doses, whereas harmful effects appear at higher concentrations.
The findings of this review confirm that novel studies are necessary to address whether Nrf2-targeting may be a safe therapeutic approach to decrease renal disease progression in humans.
肾脏疾病是一个严重的健康问题，其发病率和患病率不断上升。氧化应激和炎症在肾脏疾病的发病机制和进展中起关键作用。因此，降低氧化应激的治疗方法应受到关注。
本综述旨在全面、更新地概述由核因子红细胞2相关因子2（Nrf2）介导的保护机制，描述靶向Nrf2的新型化合物，其预防肾脏疾病的有效性以及针对这种病理状况正在进行的临床试验。
我们对文献数据库进行了结构化检索，以查找有关Nrf2激活剂和肾脏疾病的同行评审研究。
转录因子Nrf2是细胞对氧化剂和炎症抗性的新兴调节因子。Nrf2控制一些细胞保护和抗炎基因的基础表达和诱导表达，这些基因调节氧化剂暴露的生理和病理生理结果。我们分析了大量研究结果，表明Nrf2的诱导可预防氧化应激并调节急性肾损伤和慢性肾病进展中的炎症。然而，在人类中进行的临床试验很少。最近的研究表明，在低剂量下观察到Nrf2激活的肾脏保护作用，而在较高浓度下则出现有害作用。
本综述的结果证实，有必要进行新的研究，以确定靶向Nrf2是否可能是一种安全的治疗方法，以减少人类肾脏疾病进展。
