摘要
背景:肾脏疾病是一个严重的健康问题,发病率和流行率日益增加。氧化应激和炎症在肾病的发病和进展中起关键作用。因此,降低氧化应激的治疗方法应该是有意义的。 目的:本综述的目的是提供一个全面和最新的Nrf2(核因子红细胞2相关因子2)介导的保护机制的概述,描述的新型化合物,目标Nrf2,预防肾脏疾病的有效性和正在进行这个病理状态的临床试验。 方法:我们对有关Nrf2激活因子和肾脏疾病的文献进行了同行评议研究的书目数据库的结构化搜索。 结果:转录因子Nrf2是细胞抵抗氧化剂和炎症的新兴调节剂。 Nrf2控制一些细胞保护和抗炎基因的基础和诱导表达,调节氧化剂暴露的生理和病理生理结果。我们已经分析了大量的研究结果,显示Nrf2诱导保护免受氧化应激,并调节急性肾损伤和慢性肾病进展中的炎症。然而,很少有人在临床试验中进行。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,而在较高浓度下出现有害作用。 结论:这次审查的结果证实,新的研究是必要的,以解决是否Nrf2靶向可能是一个安全的治疗方法,以减少人类肾脏疾病进展。
关键词: Nrf2,氧化,炎症,急慢性肾损伤,肾功能损害,治疗。
Current Medicinal Chemistry
Title:Targeting Nrf2 in Protection Against Renal Disease
Volume: 24 Issue: 33
关键词: Nrf2,氧化,炎症,急慢性肾损伤,肾功能损害,治疗。
摘要: Background: 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.
Objective: 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.
Methods: We undertook a structured search of bibliographic databases for peer-reviewed research in literature about Nrf2 activators and renal disease.
Results: 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.
Conclusion: 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.
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Cite this article as:
Targeting Nrf2 in Protection Against Renal Disease, Current Medicinal Chemistry 2017; 24 (33) . https://dx.doi.org/10.2174/0929867324666170511120814
DOI https://dx.doi.org/10.2174/0929867324666170511120814 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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