scholarly journals Role of Nuclear Factor Erythroid 2-Related Factor 2 in Diabetic Nephropathy

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Wenpeng Cui ◽  
Xu Min ◽  
Xiaohong Xu ◽  
Bing Du ◽  
Ping Luo
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Cellular Response ◽  
Therapeutic Effects ◽  
Related Factor ◽  
Nuclear Factor ◽  
Urinary Protein Level ◽  
Nrf2 Activation ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy (DN) is manifested as increased urinary protein level, decreased glomerular filtration rate, and final renal dysfunction. DN is the leading cause of end-stage renal disease worldwide and causes a huge societal healthcare burden. Since satisfied treatments are still limited, exploring new strategies for the treatment of this disease is urgently needed. Oxidative stress takes part in the initiation and development of DN. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) plays a key role in the cellular response to oxidative stress. Thus, activation of Nrf2 seems to be a new choice for the treatment of DN. In current review, we discussed and summarized the therapeutic effects of Nrf2 activation on DN from both basic and clinical studies.

scholarly journals Therapeutic Effects of Specialized Pro-Resolving Lipids Mediators on Cardiac Fibrosis via NRF2 Activation

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1259
Author(s):  
Gyeoung Jin Kang ◽  
Eun Ji Kim ◽  
Chang Hoon Lee
Keyword(s):  
Oxidative Stress ◽  
Cardiac Fibrosis ◽  
Lipid Mediators ◽  
Therapeutic Effects ◽  
Related Factor ◽  
Nuclear Factor ◽  
Docosahexanoic Acid ◽  
Nrf2 Activation ◽  
The World ◽  
Polyunsaturated Lipids

Heart disease is the number one mortality disease in the world. In particular, cardiac fibrosis is considered as a major factor causing myocardial infarction and heart failure. In particular, oxidative stress is a major cause of heart fibrosis. In order to control such oxidative stress, the importance of nuclear factor erythropoietin 2 related factor 2 (NRF2) has recently been highlighted. In this review, we will discuss the activation of NRF2 by docosahexanoic acid (DHA), eicosapentaenoic acid (EPA), and the specialized pro-resolving lipid mediators (SPMs) derived from polyunsaturated lipids, including DHA and EPA. Additionally, we will discuss their effects on cardiac fibrosis via NRF2 activation.

scholarly journals NRF2 as a regulator of cell metabolism and inflammation in cancer

2020 ◽  
Vol 41 (4) ◽  
pp. 405-416 ◽  
Author(s):  
Feng He ◽  
Laura Antonucci ◽  
Michael Karin
Keyword(s):  
Oxidative Stress ◽  
Cancer Risk ◽  
Poor Prognosis ◽  
Cell Metabolism ◽  
Transcriptional Regulator ◽  
Negative Control ◽  
Metabolic Reprogramming ◽  
Related Factor ◽  
Nuclear Factor ◽  
Nrf2 Activation

Abstract Nuclear factor erythroid 2-related factor 2 (NRF2) is a master transcriptional regulator of genes whose products defend our cells for toxic and oxidative insults. Although NRF2 activation may reduce cancer risk by suppressing oxidative stress and tumor-promoting inflammation, many cancers exhibit elevated NRF2 activity either due to mutations that disrupt the negative control of NRF2 activity or other factors. Importantly, NRF2 activation is associated with poor prognosis and NRF2 has turned out to be a key activator of cancer-supportive anabolic metabolism. In this review, we summarize the diverse roles played by NRF2 in cancer focusing on metabolic reprogramming and tumor-promoting inflammation.

scholarly journals Serum Prolidase Activity and Oxidative Stress in Diabetic Nephropathy and End Stage Renal Disease: A Correlative Study with Glucose and Creatinine

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Akhilesh Kumar Verma ◽  
Subhash Chandra ◽  
Rana Gopal Singh ◽  
Tej Bali Singh ◽  
Shalabh Srivastava ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Blood Glucose ◽  
Renal Disease ◽  
Serum Creatinine ◽  
End Stage Renal Disease ◽  
Prolidase Activity ◽  
Stage Renal Disease ◽  
End Stage ◽  
And Oxidative Stress

Association of oxidative stress and serum prolidase activity (SPA) has been reported in many chronic diseases. The study was aimed at evaluating the correlation of glucose and creatinine to SPA and oxidative stress in patients with diabetic nephropathy (DN) and end stage renal disease (ESRD) concerned with T2DM. 50 healthy volunteers, 50 patients with T2DM, 86 patients with DN, and 43 patients with ESRD were considered as control-1, control-2, case-1, and case-2, respectively. Blood glucose, creatinine, SPA, total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) were measured by colorimetric tests. SPA, TOS, and OSI were significantly increased in case-1 and case-2 than control-1 and control-2, while TAS was significantly decreased(P<0.001). Blood glucose was linearly correlated to SPA, TOS, TAS, and OSI in control-2, case-1 and case-2(P<0.001). Serum creatinine was linearly correlated with SPA, TOS, TAS and OSI in control-2 and case-1(P<0.001). In case-2, serum creatinine was significantly correlated with SPA only(P<0.001). Thus, the study concluded that SPA and oxidative stress significantly correlated with blood glucose and creatinine. SPA, TOS, TAS, and OSI can be used as biomarkers for diagnosis of kidney damage.

Epimedium koreanum Ameliorates Oxidative Stress-Mediated Liver Injury by Activating Nuclear Factor Erythroid 2-Related Factor 2

2018 ◽  
Vol 46 (02) ◽  
pp. 469-488 ◽  
Author(s):  
Ji Yun Jung ◽  
Sang Mi Park ◽  
Hae Li Ko ◽  
Jong Rok Lee ◽  
Chung A Park ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Liver Injury ◽  
Hepg2 Cells ◽  
Liver Diseases ◽  
Caspase 3 ◽  
Glutathione Depletion ◽  
Related Factor ◽  
Nuclear Factor ◽  
Nrf2 Activation ◽  
Anti Oxidant

Oxidative stress induced by reactive oxygen species is the main cause of various liver diseases. This study investigated the hepatoprotective effect of Epimedium koreanum Nakai water extract (EKE) against arachidonic acid (AA)[Formula: see text][Formula: see text][Formula: see text]iron-mediated cytotoxicity in HepG2 cells and carbon tetrachloride (CCl4-)-mediated acute liver injury in mice. Pretreatment with EKE (30 and 100[Formula: see text][Formula: see text]g/mL) significantly inhibited AA[Formula: see text][Formula: see text][Formula: see text]iron-mediated cytotoxicity in HepG2 cells by preventing changes in the expression of cleaved caspase-3 and poly(ADP-ribose) polymerase. EKE attenuated hydrogen peroxide production, glutathione depletion, and mitochondrial membrane dysfunction. EKE also increased the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), transactivated anti-oxidant response element harboring luciferase activity, and induced the expression of anti-oxidant genes. Furthermore, the cytoprotective effect of EKE against AA[Formula: see text][Formula: see text][Formula: see text]iron was blocked in Nrf2 knockout cells. Ultra-performance liquid chromatography analysis showed that EKE contained icariin, icaritin, and quercetin; icaritin and quercetin were both found to protect HepG2 cells from AA[Formula: see text][Formula: see text][Formula: see text]iron via Nrf2 activation. In a CCl4-induced mouse model of liver injury, pretreatment with EKE (300[Formula: see text]mg/kg) for four consecutive days ameliorated CCl4-mediated increases in serum aspartate aminotransferase activity, histological activity index, hepatic parenchyma degeneration, and inflammatory cell infiltration. EKE also decreased the number of nitrotyrosine-, 4-hydroxynonenal-, cleaved caspase-3-, and cleaved poly(ADP-ribose) polymerase-positive cells in hepatic tissues. These results suggest EKE is a promising candidate for the prevention or treatment of oxidative stress-related liver diseases via Nrf2 activation.

scholarly journals GC-MS-based Metabolomic Profiling of Thymoquinone in Streptozotocin-induced Diabetic Nephropathy in Rats

2017 ◽  
Vol 12 (4) ◽  
pp. 1934578X1701200 ◽  
Author(s):  
Mohammad Raish ◽  
Ajaz Ahmad ◽  
Basit L. Jan ◽  
Khalid M. Alkharfy ◽  
Kazi Mohsin ◽  
...  
Keyword(s):  
Amino Acids ◽  
Fatty Acids ◽  
Diabetic Nephropathy ◽  
Therapeutic Interventions ◽  
Gas Chromatography Mass Spectrometry ◽  
Therapeutic Effects ◽  
Serum Samples ◽  
Metabolomic Profiling ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy is a common complication of diabetes mellitus and one of the major etiologies of end-stage renal disease. Specific therapeutic interventions are necessary to treat such complications. The present study was designed to investigate the metabolomic changes induced by thymoquinone for the treatment of diabetic nephropathy, using a rodent model. Rats were divided into three different groups (n = 6 each): control, diabetic, and thymoquinone-treated diabetic groups. Metabolites in serum samples were analyzed via gas chromatography-mass spectrometry. Multiple changes were observed, including those related to the metabolism of amino acids and fatty acids. The correlation analysis suggested that treatment with thymoquinone led to the reversal of diabetic nephropathy that was associated with modulations in the metabolism and proteolysis of amino acids, fatty acids, glycerol phospholipids, and organic acids. In addition, we explored the mechanisms linking the metabolic profiling of diabetic nephropathy, with a particular emphasis on the potential roles of increased reactive oxygen species production and mitochondrial dysfunctions. Our findings demonstrated that metabolomic profiling provided significant insights into the basic mechanisms of diabetic nephropathy and the therapeutic effects of thymoquinone.

Salvia miltiorrhiza Lipophilic Fraction Attenuates Oxidative Stress in Diabetic Nephropathy through Activation of Nuclear Factor Erythroid 2-Related Factor 2

2017 ◽  
Vol 45 (07) ◽  
pp. 1441-1457 ◽  
Author(s):  
Lin An ◽  
Mei Zhou ◽  
Faiz M. M. T. Marikar ◽  
Xue-Wen Hu ◽  
Qiu-Yun Miao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
High Glucose ◽  
Mesangial Cells ◽  
Salvia Miltiorrhiza ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Nuclear Factor

Diabetic nephropathy (DN) is a common cause of chronic kidney disease and end-stage renal disease, which can be triggered by oxidative stress. In this study, we investigated the renoprotective effect of the ethyl acetate extract of Salvia miltiorrhiza (EASM) on DN and examined the underlying molecular mechanism. We observed that EASM treatment attenuated metabolic abnormalities associated with hyperglycemic conditions in the experimental DN model. In streptozotocin (STZ)-induced mice, EASM treatment reduced albuminuria, improved renal function and alleviated the pathological alterations within the glomerulus. To mimic the hyperglycemic conditions in DN patients, we used high glucose (25[Formula: see text]mmol/L) media to stimulate mouse mesangial cells (MMCs), and EASM inhibited high glucose-induced reactive oxygen species. We also observed that EASM enhanced the expression of nuclear factor erythroid-2-related factor 2 (Nrf2), which mediated the anti-oxidant response, and its downstream gene heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1) with concomitant decrease of expression of kelch-like ECH-associated protein 1 (keap1) both in vitro and in vivo. Taken together, these results suggest that EASM alleviates the progression of DN and this might be associated with activation of Nrf2.

scholarly journals The Role of Non-coding RNAs in Diabetic Nephropathy-Related Oxidative Stress

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiaoyun He ◽  
Gaoyan Kuang ◽  
Yi Zuo ◽  
Shuangxi Li ◽  
Suxian Zhou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Interstitial Fibrosis ◽  
Rna Molecules ◽  
Non Coding Rnas ◽  
Molecular Therapeutic ◽  
Stage Renal Disease ◽  
End Stage ◽  
Molecular Therapeutic Targets

Diabetic nephropathy (DN) is one of the main complications of diabetes and the main cause of diabetic end-stage renal disease, which is often fatal. DN is usually characterized by progressive renal interstitial fibrosis, which is closely related to the excessive accumulation of extracellular matrix and oxidative stress. Non-coding RNAs (ncRNAs) are RNA molecules expressed in eukaryotic cells that are not translated into proteins. They are widely involved in the regulation of biological processes, such as, chromatin remodeling, transcription, post-transcriptional modification, and signal transduction. Recent studies have shown that ncRNAs play an important role in the occurrence and development of DN and participate in the regulation of oxidative stress in DN. This review clarifies the functions and mechanisms of ncRNAs in DN-related oxidative stress, providing valuable insights into the prevention, early diagnosis, and molecular therapeutic targets of DN.

scholarly journals Nrf2 activation as a future target of therapy for chronic diseases

2014 ◽  
Vol 4 (12) ◽  
pp. 510 ◽  
Author(s):  
Rame Taha ◽  
Gilbert Blaise
Keyword(s):  
Oxidative Stress ◽  
Chronic Diseases ◽  
Therapeutic Potential ◽  
Antioxidant Response ◽  
Premature Aging ◽  
Therapeutic Effects ◽  
Related Factor ◽  
Nrf2 Activation ◽  
Inflammatory Drugs ◽  
Therapeutic Alternatives

Background: Chronic inflammation integrally related to oxidative stress has been increasingly recognized as a contributing factor in various chronic diseases such as neurodegenerative diseases, pulmonary diseases, metabolic syndrome, and cardiovascular diseases as well as premature aging. Thus, inhibiting this vicious circle has the potential to delay, prevent progression, and treat those diseases. However, adverse effects of current anti-inflammatory drugs and the failure of exogenous antioxidant encourage scientists to develop new therapeutic alternatives. The nuclear factor E2-related factor 2 (Nrf2) is the transcription factor that is responsible for the expression of antioxidant response element (ARE)-regulated genes and have been described as having many therapeutic effects. In this review, we have discussed the role of oxidative stress in various chronic diseases. Furthermore, we have also explored various novel ways to activate Nrf2 either directly or indirectly, which may have therapeutic potential in attenuating oxidative stress, inflammation and mitochondrial dysfunction that contributes to chronic diseases.Keywords: Oxidative stress, Mitochondria, Inflammation, Nrf2, Nutrition, Chronic diseases

scholarly journals NRF2: A potential target for the treatment of diabetic nephropathy

2021 ◽  
Vol 1 (1) ◽  
pp. 27-32
Author(s):  
Jiahui Zhang ◽  
Fnu Anshul ◽  
Joshua D. Breidenbach ◽  
Jing Liu ◽  
James Shaffner
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Defense Mechanism ◽  
Cardiovascular Effects ◽  
Related Factor ◽  
Cytotoxic Effects ◽  
Promising Target ◽  
Nrf2 Activation ◽  
Clinical Models ◽  
Inflammatory Molecules

Abstract One of the major complications of diabetes mellitus is diabetic nephropathy (DN), the pathogenesis of which is primarily driven by oxidative stress. As a major regulator of antioxidant responses, the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) has recently attracted much interest. NRF2 is a primary defense mechanism against the cytotoxic effects of oxidative stress, involving heterogeneous detoxification, the production of antioxidants and anti-inflammatory molecules, DNA repair, nuclear chaperones, and proteasome systems. A myriad of studies in pre-clinical models of DN have consistently demonstrated a beneficial effect of NRF2 activation, suggesting that NRF2 is likely a promising target for treating DN. This has been further supported by findings from clinical trials of bardoxolone methyl, an activator of NRF2, despite the unexpected adverse cardiovascular effects. This review summarizes the support for therapeutic targeting of NRF2 in DN and emphasizes the need for the optimization of NRF2-based treatment with the minimization of potential adverse effects.

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