In this review, we summarize recent literature investigating the role of NRF2 and oxidative stress in various kidney diseases, and how pharmacological modification of NRF2 signaling could play a protective role.
4-O-methylhonokiol ameliorates type 2 diabetes-induced nephropathy in mice likely by activation of AMPK-mediated fatty acid oxidation and Nrf2-mediated anti-oxidative stress.
The protective effect of Nrf2 on renal injury has been attributed to its antioxidant role, where it aids in coping with oxidative stress-associated progression of renal disease.
Taken together, our study suggested that small-molecule Keap1-Nrf2 PPI inhibitors can activate the Nrf2-based cytoprotective system and protect the kidney from inflammatory injury, raising a potential application of Keap1-Nrf2 PPI inhibitors in the treatment of inflammatory kidney disorders.
<b>Methods:</b> Electron microscopy, immunohistochemical (IHC) staining, Western blot, and real-time PCR were used to detect the expression of ACSL1and Nrf2 in ORN patients, ob/ob mice and palmitic acid (PA)-treated HK-2 cells.
Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway is a well-established antioxidant pathway in various diseases such as diabetes, renal disease, various neurodegenerative disorders such as Parkinson's disease, Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis, traumatic brain injury, etc.
Nrf2 Deficiency Upregulates Intrarenal Angiotensin-Converting Enzyme-2 and Angiotensin 1-7 Receptor Expression and Attenuates Hypertension and Nephropathy in Diabetic Mice.
In addition, D‑pinitol increased the level of sirtuin 1 (Sirt1), and the total and nuclear expression levels of nuclear erythroid factor 2‑related factor 2 (Nrf2), suggesting that activation of the Sirt1 and Nrf2 pathways may induce the cellular antioxidant system against CsA‑induced nephropathy.
This review summarizes the current issues in the treatment of kidney diseases, including clinical endpoints, Nrf2 activators as treatment options, and perspectives on pharmaceutical applications of Nrf2 activators.
The natural compound 2,3,5,4'-tetrahydroxystilbene-2-O-β-d glucoside protects against adriamycin-induced nephropathy through activating the Nrf2-Keap1 antioxidant pathway.
An increasing body of evidence supports a key role for Keap1/Nrf2 pathway in kidney diseases and renal cell carcinoma (RCC), but data concerning the molecular basis and the clinical effect of its deregulation remain incomplete.Here we present a molecular profiling of the KEAP1 and NFE2L2 genes in five different Renal Cell Carcinoma histotypes by analysing 89 tumor/normal paired tissues (clear cell Renal Carcinoma, ccRCCs; Oncocytomas; Papillary Renal Cell Carcinoma Type 1, PRCC1; Papillary Renal Cell Carcinoma Type 2, PRCC2; and Chromophobe Cell Carcinoma).A tumor-specific DNA methylation of the KEAP1 gene promoter region was found as a specific feature of the ccRCC subtype (18/37, 48.6%) and a direct correlation with mRNA levels was confirmed by in vitro 5-azacytidine treatment.
Thus, apocynin exerts antiseptic activity via the suppression of pro-inflammatory signaling pathways and the activation of cytoprotective signaling pathways, such as HO-1/Nrf-2 in RMCs, indicating that apocynin may present as a promising candidate for in vivo evaluation of a therapeutic agent for inflammation-associated renal disorders.
Loss of GSTM1, a NRF2 target, is associated with accelerated progression of hypertensive kidney disease in the African American Study of Kidney Disease (AASK).
Transcriptional regulation of renal cytoprotective genes by Nrf2 and its potential use as a therapeutic target to mitigate cisplatin-induced nephrotoxicity.