Oxidant Mechanisms in Renal Injury and Disease

Ratliff, Brian B.; Abdulmahdi, Wasan; Pawar, Rahul D.; Wolin, Michael S.

doi:10.1089/ars.2016.6665

Cited by 556 publications

(556 citation statements)

References 342 publications

(319 reference statements)

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“…Low-level ROS function as signaling molecules for cellular proliferation and vascular homeostasis under healthy conditions [14]; however, ROS accumulate massively in the kidneys due to pathological conditions caused by angiotensin II signaling [23,24], a high-salt diet [25], hypertension [23,26], inflammation [27], hyperglycemia [28] or nephrotoxic drugs [29]. …”

Section: Oxidative Stress and Kidney Diseasesmentioning

confidence: 99%

“…Kidney diseases are also thought to be related to oxidative stress [2,13,14], and basic research has generated evidence that NRF2 activation prevents kidney disease progression by protecting cells from oxidative damage. Therefore, there is a need for NRF2-activating medicines to protect against kidney diseases, for which there are currently no effective medications.…”

Section: Introductionmentioning

confidence: 99%

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Targeting the KEAP1-NRF2 System to Prevent Kidney Disease Progression

Nezu¹,

Suzuki

Yamamoto³

2017

Am J Nephrol

2,559

112

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Background: Nuclear factor erythroid 2-related factor 2 (NRF2) is a critical transcription factor for the antioxidative stress response and it activates a variety of cytoprotective genes related to redox and detoxification. NRF2 activity is regulated by the oxidative-stress sensor molecule Kelch-like ECH-associated protein 1 (KEAP1) that induces proteasomal degradation of NRF2 through ubiquitinating NRF2 under unstressed conditions. Because oxidative stress is a major pathogenic and aggravating factor for kidney diseases, the KEAP1-NRF2 system has been proposed to be a therapeutic target for renal protection. Summary: Oxidative-stress molecules, such as reactive oxygen species, accumulate in the kidneys of animal models for acute kidney injury (AKI), in which NRF2 is transiently and slightly activated. Genetic or pharmacological enhancement of NRF2 activity in the renal tubules significantly ameliorates damage related to AKI and prevents AKI progression to chronic kidney disease (CKD) by reducing oxidative stress. These beneficial effects of NRF2 activation highlight the KEAP1-NRF2 system as an important target for kidney disease treatment. However, a phase-3 clinical trial of a KEAP1 inhibitor for patients with stage 4 CKD and type-2 diabetes mellitus (T2DM) was terminated due to the occurrence of cardiovascular events. Because recent basic studies have accumulated positive effects of KEAP1 inhibitors in moderate stages of CKD, phase-2 trials have been restarted. The data from the ongoing projects demonstrate that a KEAP1 inhibitor improves the glomerular filtration rate in patients with stage 3 CKD and T2DM without safety concerns. Key Message: The KEAP1-NRF2 system is one of the most promising therapeutic targets for kidney disease, and KEAP1 inhibitors could be part of critical therapies for kidney disease.

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Section: Oxidative Stress and Kidney Diseasesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Targeting the KEAP1-NRF2 System to Prevent Kidney Disease Progression

Nezu¹,

Suzuki

Yamamoto³

2017

Am J Nephrol

2,559

112

View full text Add to dashboard Cite

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“…45) Moreover, it has been reported that all forms of acute and chronic renal injuries, regardless of species, is associated with enhanced generation of ROS, 46) which linked ROS to renal damage. Besides, cell senescence also plays a pivotal role in renal damage.…”

Section: Hfd and Hg Culture Comparisonmentioning

confidence: 99%

Resveratrol Protects against High-Fat Diet Induced Renal Pathological Damage and Cell Senescence by Activating SIRT1

Zhang

et al. 2016

Biological & Pharmaceutical Bulletin

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Obesity-related renal diseases have been a worldwide issue. Effective strategy that prevents high fat-diet induced renal damage is of great significance. Resveratrol, a natural plant polyphenol, is famous for its antioxidant activity, cardioprotective effects and anticancer properties. However whether resveratrol can play a role in the treatment of renal diseases is unknown. In this study, we added resveratrol in normal glucose or high glucose medium and provide evidences that resveratrol protects against high-glucose triggered oxidative stress and cell senescence. Moreover, mice were fed with standard diet, standard diet plus resveratrol, high-fat diet or high-fat diet plus resveratrol for 3 months, and results show that resveratrol treatment prevents high-fat diet induced renal pathological damage by activating SIRT1, a key member in the mammalian sirtuin family that response to calorie restriction life-extension method. This research confirms the potential role of resveratrol in the treatment of renal diseases and may provide an effective and convenient method to mimic the beneficial effects of calorie restriction.

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“…Oxidative stress is characterized by increased ROS and/or RNS which were indicated in both human and animal models with kidney injury (Ratliff et al, 2016). In the kidney, nitric oxide (NO) plays a great role in the regulation of physiological glomerular functions (Prabhakar, 2001).…”

Section: Discussionmentioning

confidence: 99%