scholarly journals Nrf2and Cardiovascular Defense

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Reuben Howden
Keyword(s):  
Cardiovascular Diseases ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Oxidant Stress ◽  
Antioxidant Response ◽  
Positive Outcome ◽  
Cellular Damage ◽  
Antioxidant Defenses ◽  
Related Factor ◽  
Transcription Factor Nuclear Factor

The cardiovascular system is susceptible to a group of diseases that are responsible for a larger proportion of morbidity and mortality than any other disease. Many cardiovascular diseases are associated with a failure of defenses against oxidative stress-induced cellular damage and/or death, leading to organ dysfunction. The pleiotropic transcription factor, nuclear factor-erythroid (NF-E) 2-related factor 2 (Nrf2), regulates the expression of antioxidant enzymes and proteins through the antioxidant response element.Nrf2is an important component in antioxidant defenses in cardiovascular diseases such as atherosclerosis, hypertension, and heart failure.Nrf2is also involved in protection against oxidant stress during the processes of ischemia-reperfusion injury and aging. However, evidence suggests thatNrf2activity does not always lead to a positive outcome and may accelerate the pathogenesis of some cardiovascular diseases (e.g., atherosclerosis). The precise conditions under whichNrf2acts to attenuate or stimulate cardiovascular disease processes are unclear. Further studies on the cellular environments related to cardiovascular diseases that influenceNrf2pathways are required beforeNrf2can be considered a therapeutic target for the treatment of cardiovascular diseases.

Abstract 264: Nitrite Therapy Ameliorates Myocardial Injury via H2S and Nuclear Factor-Erythroid 2-Related Factor 2 (Nrf2)-Dependent Signaling in Chronic Heart Failure

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Kazi N Islam ◽  
Erminia Donnarumma ◽  
Shashi Bhushan ◽  
David J Lefer
Keyword(s):  
Heart Failure ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Antioxidant Defenses ◽  
Left Ventricular Ejection ◽  
Related Factor ◽  
Mrna Levels ◽  
Ventricular Ejection Fraction ◽  
Nrf2 Activation

Background: Nitric oxide (NO) and hydrogen sulfide (H 2 S) are reduced in congestive heart failure. Recent studies suggest cross-talk between NO and H 2 S signaling. We previously reported that sodium nitrite (NaNO 2 ) significantly ameliorates myocardial ischemia-reperfusion injury and heart failure. Nrf2 regulates the expression of antioxidant protein genes and is upregulated by H 2 S. We examined the effects of NaNO 2 therapy on endogenous H 2 S bioavailability and Nrf2 activation in mice subjected to ischemia-induced heart failure. Materials and Methods: Mice underwent 60 min. of left coronary artery occlusion and 4 weeks (WKS) of reperfusion. NaNO 2 (165 μg/kg) or saline vehicle (VEH) was administered at reperfusion and then in drinking water (100 mg/L) for 4 wks. Left ventricular ejection fraction (LVEF) was determined at baseline and 4 wks of reperfusion. Myocardial tissue was collected and analyzed for oxidative stress status and respective gene/protein levels. Results: NaNO 2 therapy preserved LVEF (47 ± 4% vs. 32 ± 4%, p < 0.01) and LV diastolic and systolic dimensions (LVEDD/LVESD; 4.0/3.1 mm vs. 4.5/3.9 mm, p < 0.05) at 4 wks. MDA and protein carbonyl contents were significantly reduced in NaNO 2 treated mice as compared to VEH. NaNO 2 markedly increased expression of CuZn-superoxide dismutase and catalase at 4 wks. Furthermore, NaNO 2 increased mRNA levels of H 2 S producing enzymes and H 2 S bioavailabilty. Cardiac Nrf2 activation was also observed with NaNO 2 therapy. Conclusions: Our results demonstrate that NaNO 2 therapy significantly improves left ventricular function via by increasing H 2 S bioavailability, activation of Nrf2, and increased antioxidant defenses.1

scholarly journals Kaempferol Ameliorates Oxygen-Glucose Deprivation/Reoxygenation-Induced Neuronal Ferroptosis by Activating Nrf2/SLC7A11/GPX4 Axis

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 923
Author(s):  
Yuan Yuan ◽  
Yanyu Zhai ◽  
Jingjiong Chen ◽  
Xiaofeng Xu ◽  
Hongmei Wang
Keyword(s):  
Lipid Peroxidation ◽  
Cell Death ◽  
Antioxidant Capacity ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Related Factor ◽  
Protective Effects

Kaempferol has been shown to protect cells against cerebral ischemia/reperfusion injury through inhibition of apoptosis. In the present study, we sought to investigate whether ferroptosis is involved in the oxygen-glucose deprivation/reperfusion (OGD/R)-induced neuronal injury and the effects of kaempferol on ferroptosis in OGD/R-treated neurons. Western blot, immunofluorescence, and transmission electron microscopy were used to analyze ferroptosis, whereas cell death was detected using lactate dehydrogenase (LDH) release. We found that OGD/R attenuated SLC7A11 and glutathione peroxidase 4 (GPX4) levels as well as decreased endogenous antioxidants including nicotinamide adenine dinucleotide phosphate (NADPH), glutathione (GSH), and superoxide dismutase (SOD) in neurons. Notably, OGD/R enhanced the accumulation of lipid peroxidation, leading to the induction of ferroptosis in neurons. However, kaempferol activated nuclear factor-E2-related factor 2 (Nrf2)/SLC7A11/GPX4 signaling, augmented antioxidant capacity, and suppressed the accumulation of lipid peroxidation in OGD/R-treated neurons. Furthermore, kaempferol significantly reversed OGD/R-induced ferroptosis. Nevertheless, inhibition of Nrf2 by ML385 blocked the protective effects of kaempferol on antioxidant capacity, lipid peroxidation, and ferroptosis in OGD/R-treated neurons. These results suggest that ferroptosis may be a significant cause of cell death associated with OGD/R. Kaempferol provides protection from OGD/R-induced ferroptosis partly by activating Nrf2/SLC7A11/GPX4 signaling pathway.

scholarly journals Immune‐Responsive Gene 1/Itaconate Activates Nuclear Factor Erythroid 2–Related Factor 2 in Hepatocytes to Protect Against Liver Ischemia–Reperfusion Injury

Hepatology ◽  
2020 ◽  
Vol 72 (4) ◽  
pp. 1394-1411 ◽  
Author(s):  
Zhongjie Yi ◽  
Meihong Deng ◽  
Melanie J. Scott ◽  
Guang Fu ◽  
Patricia A. Loughran ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Related Factor ◽  
Nuclear Factor ◽  
Liver Ischemia ◽  
Responsive Gene

scholarly journals Assessing the Efficacy of Dietary Selenomethionine Supplementation in the Setting of Cardiac Ischemia/Reperfusion Injury

Antioxidants ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 546 ◽  
Author(s):  
Leila Reyes ◽  
David P. Bishop ◽  
Clare L. Hawkins ◽  
Benjamin S. Rayner
Keyword(s):  
Cardiac Myocyte ◽  
Hypochlorous Acid ◽  
Ischemia Reperfusion Injury ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Cytosolic Calcium ◽  
Cardiac Ischemia ◽  
Cellular Damage

Oxidative stress is a major hallmark of cardiac ischemia/reperfusion (I/R) injury. This partly arises from the presence of activated phagocytes releasing myeloperoxidase (MPO) and its production of hypochlorous acid (HOCl). The dietary supplement selenomethionine (SeMet) has been shown to bolster endogenous antioxidant processes as well as readily react with MPO-derived oxidants. The aim of this study was to assess whether supplementation with SeMet could modulate the extent of cellular damage observed in an in vitro cardiac myocyte model exposed to (patho)-physiological levels of HOCl and an in vivo rat model of cardiac I/R injury. Exposure of the H9c2 cardiac myoblast cell line to HOCl resulted in a dose-dependent increase in necrotic cell death, which could be prevented by SeMet supplementation and was attributed to SeMet preventing the HOCl-induced loss of mitochondrial inner trans-membrane potential, and the associated cytosolic calcium accumulation. This protection was credited primarily to the direct oxidant scavenging ability of SeMet, with a minor contribution arising from the ability of SeMet to bolster cardiac myoblast glutathione peroxidase (GPx) activity. In vivo, a significant increase in selenium levels in the plasma and heart tissue were seen in male Wistar rats fed a diet supplemented with 2 mg kg−1 SeMet compared to controls. However, SeMet-supplementation demonstrated only limited improvement in heart function and did not result in better heart remodelling following I/R injury. These data indicate that SeMet supplementation is of potential benefit within pathological settings where excessive HOCl is known to be generated but has limited efficacy as a therapeutic agent for the treatment of heart attack.

Vinpocetine protects liver against ischemia–reperfusion injury

2013 ◽  
Vol 91 (12) ◽  
pp. 1064-1070 ◽  
Author(s):  
Hala Fahmy Zaki ◽  
Rania Mohsen Abdelsalam
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Liver Lipid ◽  
Cerebrovascular Disorders ◽  
Cellular Damage ◽  
Dependent Manner ◽  
Oxidative Stress Biomarkers ◽  
Serum Transaminases

Hepatic ischemia–reperfusion (IR) injury is a clinical problem that leads to cellular damage and organ dysfunction mediated mainly via production of reactive oxygen species and inflammatory cytokines. Vinpocetine has long been used in cerebrovascular disorders. This study aimed to explore the protective effect of vinpocetine in IR injury to the liver. Ischemia was induced in rats by clamping the common hepatic artery and portal vein for 30 min followed by 30 min of reperfusion. Serum transaminases and liver lactate dehydrogenase (LDH) activities, liver inflammatory cytokines, oxidative stress biomarkers, and liver histopathology were assessed. IR resulted in marked histopathology changes in liver tissues coupled with elevations in serum transaminases and liver LDH activities. IR also increased the production of liver lipid peroxides, nitric oxide, and inflammatory cytokines interleukin-1β and interleukin-6, in parallel with a reduction in reduced glutathione and interleukin-10 in the liver. Pretreatment with vinpocetine protected against liver IR-induced injury, in a dose-dependent manner, as evidenced by the attenuation of oxidative stress as well as inflammatory and liver injury biomarkers. The effects of vinpocetine were comparable with that of curcumin, a natural antioxidant, and could be attributed to its antioxidant and anti-inflammatory properties.

scholarly journals Ezetimibe Prevents Ischemia/Reperfusion-Induced Oxidative Stress and Up-Regulates Nrf2/ARE and UPR Signaling Pathways

Antioxidants ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 349 ◽  
Author(s):  
Denise Peserico ◽  
Chiara Stranieri ◽  
Ulisse Garbin ◽  
Chiara Mozzini C ◽  
Elisa Danese ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Cultured Cells ◽  
Ischemia Reperfusion ◽  
Cholesterol Absorption ◽  
Antioxidant Response ◽  
Related Factor ◽  
Cellular Models ◽  
Compound C ◽  
Cholesterol Absorption Inhibitor

Background: While reperfusion is crucial for survival after an episode of ischemia, it also causes oxidative stress. Nuclear factor-E2-related factor 2 (Nrf2) and unfolded protein response (UPR) are protective against oxidative stress and endoplasmic reticulum (ER) stress. Ezetimibe, a cholesterol absorption inhibitor, has been shown to activate the AMP-activated protein kinase (AMPK)/Nrf2 pathway. In this study we evaluated whether Ezetimibe affects oxidative stress and Nrf2 and UPR gene expression in cellular models of ischemia-reperfusion (IR). Methods: Cultured cells were subjected to simulated IR with or without Ezetimibe. Results: IR significantly increased reactive oxygen species (ROS) production and the percentage of apoptotic cells without the up-regulation of Nrf2, of the related antioxidant response element (ARE) gene expression or of the pro-survival UPR activating transcription factor 6 (ATF6) gene, whereas it significantly increased the pro-apoptotic CCAAT-enhancer-binding protein homologous protein (CHOP). Ezetimibe significantly decreased the cellular ROS formation and apoptosis induced by IR. These effects were paralleled by the up-regulation of Nrf2/ARE and ATF6 gene expression and by a down-regulation of CHOP. We also found that Nrf2 activation was dependent on AMPK, since Compound C, a pan inhibitor of p-AMPK, blunted the activation of Nrf2. Conclusions: Ezetimibe counteracts IR-induced oxidative stress and induces Nrf2 and UPR pathway activation.

scholarly journals NRF2 Regulation by Noncoding RNAs in Cancers: The Present Knowledge and the Way Forward

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3621
Author(s):  
Federico Pio Fabrizio ◽  
Angelo Sparaneo ◽  
Lucia Anna Muscarella
Keyword(s):  
Noncoding Rna ◽  
Gene Network ◽  
Noncoding Rnas ◽  
Antioxidant Response ◽  
Present Knowledge ◽  
Cellular Damage ◽  
Related Factor ◽  
Nuclear Factor ◽  
Oxygen Species ◽  
Cellular Mechanisms

Nuclear factor erythroid 2-related factor 2 (NRF2) is the key transcription factor triggered by oxidative stress that moves in cells of the antioxidant response element (ARE)-antioxidant gene network against reactive oxygen species (ROS) cellular damage. In tumors, the NRF2 pathway represents one of the most intriguing pathways that promotes chemo- and radioresistance of neoplastic cells and its activity is regulated by genetic and epigenetic mechanisms; some of these being poorly investigated in cancer. The noncoding RNA (ncRNA) network is governed by microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) and modulates a variety of cellular mechanisms linked to cancer onset and progression, both at transcriptional and post-transcriptional levels. In recent years, the scientific findings about the effects of ncRNA landscape variations on NRF2 machines are rapidly increasing and need to be continuously updated. Here, we review the latest knowledge about the link between NRF2 and ncRNA networks in cancer, thus focusing on their potential translational significance as key tumor biomarkers.

scholarly journals Effect of atorvastatin on oxidative damage and inflammation in experimental hindlimb ischemia–reperfusion model

2018 ◽  
Vol 16 ◽  
pp. 205873921881266
Author(s):  
Walter A Trujillo-Rangel ◽  
Araceli Castillo-Romero ◽  
Sylvia E Totsuka-Sutto ◽  
Simón Q Rodríguez-Lara ◽  
Teresa A García-Cobián ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Cellular Damage ◽  
Healthy Controls ◽  
Transcript Levels ◽  
Loss And Damage ◽  
Ischemic Tissue ◽  
Tnf Α ◽  
Hematoxylin And Eosin Stain

Ischemia–reperfusion is defined as cellular damage after the reperfusion of ischemic tissue, and it is likely to occur in relation to various diseases and surgical procedures. The purpose of this study was to evaluate the capability of atorvastatin to prevent oxidative damage and modulate the release of proinflammatory cytokines in rat hindlimb during ischemia–reperfusion injury. The animals were divided into 4 groups (ischemia–reperfusion + vehicle, ischemia–reperfusion + atorvastatin, sham, and healthy controls) with 15 rats per group. The animals were exposed to ischemia for 6 h, followed by 24 h, 7 days, and 14 days of reperfusion. Atorvastatin was administered by gavage 14 days before ischemia–reperfusion induction. We then measured the serum concentrations and mRNA transcript levels of TNF-α, IL-1β, IL-6, IL-10, SOD2, and CAT. Hematoxylin and eosin stain were performed for histological analyses. Animals subjected to ischemia–reperfusion showed increased serum and transcript levels of TNF-α, IL-1β, IL-6, and IL-10 expressions with a concurrent increase in mRNA transcripts levels compared with sham and healthy controls. Groups treated with atorvastatin showed a significant CAT increase in the first 24 h, but CAT levels decreased at 7 and 14 days. SOD2 enzyme increased in serum without significant changes in mRNA expression. Histological analysis showed inflammatory infiltrate, microhemorrhages, and distortion of the tissue architecture in the first 7 days. At 14 days, the tissue showed loss and damage to myocytes. However, animals treated with atorvastatin showed few histological changes and a decrease in inflammatory cytokines. No significant changes in NO2, NO3, or 8-OHdG were observed. Atorvastatin showed a protective effect on the inflammation and tissue damage induced by ischemia–reperfusion in the hindlimb. The antioxidant effect of atorvastatin in the hindlimb is already unclear, and further research is needed to elucidate the molecular mechanism of this drug in the extremities.

scholarly journals Persistent oxidative stress following renal ischemia-reperfusion injury increases ANG II hemodynamic and fibrotic activity

2012 ◽  
Vol 302 (11) ◽  
pp. F1494-F1502 ◽  
Author(s):  
David P. Basile ◽  
Ellen C. Leonard ◽  
Alisa G. Beal ◽  
Devin Schleuter ◽  
Jessica Friedrich
Keyword(s):  
Oxidative Stress ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Oxidant Stress ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Ang Ii ◽  
Tissue Slices ◽  
Dual Oxidase ◽  
Renal Ischemia Reperfusion Injury

ANG II is a potent renal vasoconstrictor and profibrotic factor and its activity is enhanced by oxidative stress. We sought to determine whether renal oxidative stress was persistent following recovery from acute kidney injury (AKI) induced by ischemia-reperfusion (I/R) injury in rats and whether this resulted in increased ANG II sensitivity. Rats were allowed to recover from bilateral renal I/R injury for 5 wk and renal blood flow responses were measured. Post-AKI rats showed significantly enhanced renal vasoconstrictor responses to ANG II relative to sham-operated controls and treatment of AKI rats with apocynin (15 mM, in the drinking water) normalized these responses. Recovery from AKI for 5 wk resulted in sustained oxidant stress as indicated by increased dihydroethidium incorporation in renal tissue slices and was normalized in apocynin-treated rats. Surprisingly, the renal mRNA expression for common NADPH oxidase subunits was not altered in kidneys following recovery from AKI; however, mRNA screening using PCR arrays suggested that post-AKI rats had decreased renal Gpx3 mRNA and an increased expression other prooxidant genes such as lactoperoxidase, myeloperoxidase, and dual oxidase-1. When rats were infused for 7 days with ANG II (100 ng·kg−1·min−1), renal fibrosis was not apparent in sham-operated control rats, but it was enhanced in post-AKI rats. The profibrotic response was significantly attenuated in rats treated with apocynin. These data suggest that there is sustained renal oxidant stress following recovery from AKI that alters both renal hemodynamic and fibrotic responses to ANG II, and may contribute to the transition to chronic kidney disease following AKI.

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