{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T14:49:32Z","timestamp":1782226172438,"version":"3.54.5"},"reference-count":52,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T00:00:00Z","timestamp":1623024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2013\/08216-2"],"award-info":[{"award-number":["2013\/08216-2"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2018\/05298-1"],"award-info":[{"award-number":["2018\/05298-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>High levels of aldosterone (Aldo) trigger oxidative stress and vascular dysfunction independent of effects on blood pressure. We sought to determine whether Aldo disrupts Nrf2 signaling, the main transcriptional factor involved in antioxidant responses that aggravate cell injury. Thoracic aorta from male C57Bl\/6J mice and cultured human endothelial cells (EA.hy926) were stimulated with Aldo (100 nM) in the presence of tiron [reactive oxygen species (ROS) scavenger, eplerenone [mineralocorticoid receptor (MR) antagonist], and L-sulforaphane (SFN; Nrf2 activator). Thoracic aortas were also isolated from mice infused with Aldo (600 \u03bcg\/kg per day) for 14 days. Aldo decreased endothelium-dependent vasorelaxation and increased ROS generation, effects prevented by tiron and MR blockade. Pharmacological activation of Nrf2 with SFN abrogated Aldo-induced vascular dysfunction and ROS generation. In EA.hy926 cells, Aldo increased ROS generation, which was prevented by eplerenone, tiron, and SFN. At short times, Aldo-induced ROS generation was linked to increased Nrf2 activation. However, after three hours, Aldo decreased the nuclear accumulation of Nrf2. Increased Keap1 protein expression, but not activation of p38 MAPK, was linked to Aldo-induced reduced Nrf2 activity. Arteries from Aldo-infused mice also exhibited decreased nuclear Nrf2 and increased Keap1 expression. Our findings suggest that Aldo reduces vascular Nrf2 transcriptional activity by Keap1-dependent mechanisms, contributing to mineralocorticoid-induced vascular dysfunction.<\/jats:p>","DOI":"10.3390\/ijms22116154","type":"journal-article","created":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T13:25:43Z","timestamp":1623072343000},"page":"6154","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Aldosterone Negatively Regulates Nrf2 Activity: An Additional Mechanism Contributing to Oxidative Stress and Vascular Dysfunction by Aldosterone"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5967-1576","authenticated-orcid":false,"given":"Daniel","family":"Rodrigues","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, 14049-900 Ribeirao Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0780-4290","authenticated-orcid":false,"given":"Tiago J.","family":"Costa","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, 14049-900 Ribeirao Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6623-7946","authenticated-orcid":false,"given":"Josiane F.","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, 14049-900 Ribeirao Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9143-0193","authenticated-orcid":false,"given":"Jos\u00e9 Teles de Oliveira","family":"Neto","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, 14049-900 Ribeirao Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliano V.","family":"Alves","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, 14049-900 Ribeirao Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline G.","family":"Fedoce","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, 14049-900 Ribeirao Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael Menezes","family":"Costa","sequence":"additional","affiliation":[{"name":"Health Sciences Special Academic Unit, Federal University of Jatai, 75804-020 Jata\u00ed, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9446-0707","authenticated-orcid":false,"given":"Rita C.","family":"Tostes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Ribeirao Preto Medical School, University of Sao Paulo, 14049-900 Ribeirao Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1161\/01.CIR.25.6.1015","article-title":"Hormones and the Pathogenesis of Congestive Heart Failure: Vasopressin, Aldosterone, And Angiotensin Ii","volume":"25","author":"Laragh","year":"1962","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.cjca.2012.03.010","article-title":"Resistant Hypertension and Aldosterone: An Update","volume":"28","author":"Clark","year":"2012","journal-title":"Can. J. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1210\/jc.2002-021443","article-title":"Aldosterone Function in Diabetes Mellitus: Effects on Cardiovascular and Renal Disease","volume":"88","author":"Mcfarlane","year":"2003","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1093\/ajh\/hpw003","article-title":"The Role of Aldosterone in Obesity-Related Hypertension","volume":"29","author":"Kawarazaki","year":"2016","journal-title":"Am. J. Hypertens."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1161\/HYPERTENSIONAHA.107.109439","article-title":"Aldosterone and Metabolic Syndrome","volume":"51","author":"Krug","year":"2008","journal-title":"Hypertension"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1159\/000345243","article-title":"Vascular Actions of Aldosterone","volume":"50","author":"Briet","year":"2013","journal-title":"J. Vasc. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"T125","DOI":"10.1530\/JOE-16-0600","article-title":"30 Years of the Mineralocorticoid Receptor: Mineralocorticoid Receptor Antagonists: 60 Years Of Research and Development","volume":"234","author":"Kolkhof","year":"2017","journal-title":"J. Endocrinol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1056\/NEJM199909023411001","article-title":"The Effect of Spironolactone on Morbidity and Mortality in Patients with Severe Heart Failure. Randomized Aldactone Evaluation Study Investigators","volume":"341","author":"Pitt","year":"1999","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1056\/NEJMoa030207","article-title":"Eplerenone, a Selective Aldosterone Blocker, in Patients with Left Ventricular Dysfunction after Myocardial Infarction","volume":"348","author":"Pitt","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"R453","DOI":"10.1016\/j.cub.2014.03.034","article-title":"Ros Function in Redox Signaling and Oxidative Stress","volume":"24","author":"Schieber","year":"2014","journal-title":"Curr. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/s41580-020-0230-3","article-title":"Reactive Oxygen Species (Ros) as Pleiotropic Physiological Signalling Agents","volume":"21","author":"Sies","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1080\/10715762.2018.1457217","article-title":"Ros And Rns Signalling: Adaptive Redox Switches through Oxidative\/Nitrosative Protein Modifications","volume":"52","author":"Moldogazieva","year":"2018","journal-title":"Free Radic. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8416763","DOI":"10.1155\/2017\/8416763","article-title":"Oxidative Stress: Harms and Benefits for Human Health","volume":"2017","author":"Pizzino","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1161\/01.HYP.0000154365.30593.d3","article-title":"Aldosterone Activates Vascular P38map Kinase and Nadph Oxidase via c-Src","volume":"45","author":"Callera","year":"2005","journal-title":"Hypertension"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1815","DOI":"10.1097\/HJH.0000000000000259","article-title":"Chronic Aldosterone Administration Causes Nox2-Mediated Increases in Reactive Oxygen Species Production and Endothelial Dysfunction in the Cerebral Circulation","volume":"32","author":"Chrissobolis","year":"2014","journal-title":"J. Hypertens."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1291\/hypres.31.363","article-title":"Aldosterone Nongenomically Produces Nadph Oxidase\u2013Dependent Reactive Oxygen Species And Induces Myocyte Apoptosis","volume":"31","author":"Hayashi","year":"2008","journal-title":"Hypertens. Res."},{"key":"ref_17","first-page":"4033","article-title":"Aldosterone Promotes Renal Interstitial Fibrosis via the Aif-1\/Akt\/Mtor Signaling Pathway","volume":"20","author":"Yuan","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1101\/gad.13.1.76","article-title":"Keap1 Represses Nuclear Activation of Antioxidant Responsive Elements by Nrf2 Through Binding to the Amino-Terminal Neh2 Domain","volume":"13","author":"Itoh","year":"1999","journal-title":"Genes Dev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1016\/j.freeradbiomed.2009.07.035","article-title":"Nrf2:Inrf2 (Keap1) Signaling in Oxidative Stress","volume":"47","author":"Kaspar","year":"2009","journal-title":"Free Radic. Biol. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8477","DOI":"10.1128\/MCB.24.19.8477-8486.2004","article-title":"The Keap1-Btb Protein is an Adaptor that Bridges Nrf2 to A Cul3-Based E3 Ligase: Oxidative Stress Sensing by A Cul3-Keap1 Ligase","volume":"24","author":"Cullinan","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"44675","DOI":"10.1074\/jbc.M307633200","article-title":"Phosphorylation of Nrf2 at Ser40 by Protein Kinase C in Response to Antioxidants Leads to the Release of Nrf2 from Inrf2, but is not Required for Nrf2 Stabilization\/Accumulation in the Nucleus and Transcriptional Activation of Antioxidant Response Element-Mediated Nad(P)H:Quinone Oxidoreductase-1 Gene Expression","volume":"278","author":"Bloom","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.freeradbiomed.2013.02.008","article-title":"Regulation of Nrf2-An Update","volume":"66","author":"Niture","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"148","DOI":"10.7150\/ijbs.28874","article-title":"Sulforaphane Attenuates Angiotensin Ii-Induced Vascular Smooth Muscle Cell Migration via Suppression of Nox4\/Ros\/Nrf2 Signaling","volume":"15","author":"Zhang","year":"2019","journal-title":"Int. J. Biol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"154002","DOI":"10.1016\/j.metabol.2019.154002","article-title":"Protective Effects of Sulforaphane on Type 2 Diabetes-Induced Cardiomyopathy via Ampk-Mediated Activation of Lipid Metabolic Pathways and Nrf2 Function","volume":"102","author":"Sun","year":"2020","journal-title":"Metab. Clin. Exp."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.redox.2017.12.016","article-title":"Sulforaphane Prevents Angiotensin Ii-Induced Cardiomyopathy by Activation of Nrf2 via Stimulating the Akt\/Gsk-3\u00df\/Fyn Pathway","volume":"15","author":"Xin","year":"2018","journal-title":"Redox Biol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.yjmcc.2013.01.008","article-title":"Prevention by Sulforaphane of Diabetic Cardiomyopathy is Associated with Up-Regulation of Nrf2 Expression and Transcription Activation","volume":"57","author":"Bai","year":"2013","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/hr.2017.83","article-title":"Role of Bardoxolone Methyl, a Nuclear Factor Erythroid 2-Related Factor 2 Activator, in Aldosterone- and Salt-Induced Renal Injury","volume":"41","author":"Hisamichi","year":"2018","journal-title":"Hypertens. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/ncpneph0575","article-title":"The Incidence and Implications of Aldosterone Breakthrough","volume":"3","author":"Bomback","year":"2007","journal-title":"Nat. Clin. Pract. Nephrol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1002\/j.1550-8528.1999.tb00418.x","article-title":"Visceral Obesity and Insulin Resistance are Associated with Plasma Aldosterone Levels in Women","volume":"7","author":"Goodfriend","year":"1999","journal-title":"Obes. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"T107","DOI":"10.1530\/JOE-16-0659","article-title":"30 Years of the Mineralocorticoid Receptor: Nongenomic Effects via the Mineralocorticoid Receptor","volume":"234","author":"Ruhs","year":"2017","journal-title":"J. Endocrinol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.yexcr.2016.06.009","article-title":"Epidermal Growth Factor Receptor Signaling Mediates Aldosterone-Induced Profibrotic Responses in Kidney","volume":"346","author":"Sheng","year":"2016","journal-title":"Exp. Cell Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"C532","DOI":"10.1152\/ajpcell.00203.2012","article-title":"Aldosterone Mediates its Rapid Effects in Vascular Endothelial Cells through Gper Activation","volume":"304","author":"Gros","year":"2013","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1093\/cvr\/cvaa075","article-title":"Aldosterone-Induced Hypertension ss Sex-Dependent, Mediated by T Cells and Sensitive to Gper Activation","volume":"117","author":"Dinh","year":"2020","journal-title":"Cardiovasc. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.tplants.2016.08.002","article-title":"Ros Are Good","volume":"22","author":"Mittler","year":"2017","journal-title":"Trends Plant Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.freeradbiomed.2020.11.021","article-title":"The Homeostatic Role of Hydrogen Peroxide, Superoxide Anion and Nitric Oxide in The Vasculature","volume":"162","author":"Costa","year":"2021","journal-title":"Free Radic. Biol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2906","DOI":"10.1681\/ASN.2005040390","article-title":"Aldosterone Stimulates Reactive Oxygen Species Production through Activation of Nadph Oxidase in Rat Mesangial Cells","volume":"16","author":"Miyata","year":"2005","journal-title":"J. Am. Soc. Nephrol. Jasn"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1161\/01.HYP.0000176236.55322.18","article-title":"Aldosterone Stimulates Matrix Metalloproteinases and Reactive Oxygen Species in Adult Rat Ventricular Cardiomyocytes","volume":"46","author":"Rude","year":"2005","journal-title":"Hypertension"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1089\/ars.2005.7.1294","article-title":"Eplerenone Reduces Oxidative Stress and Enhances Enos in Shr: Vascular Functional and Structural Consequences","volume":"7","author":"Cediel","year":"2005","journal-title":"Antioxid. Redox Signal."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Ferreira, N.S., Bruder-Nascimento, T., Pereira, C.A., Zanotto, C.Z., Prado, D.S., Silva, J.F., Rassi, D.M., Foss-Freitas, M.C., Alves-Filho, J.C., and Carlos, D. (2019). Nlrp3 Inflammasome and Mineralocorticoid Receptors are Associated with Vascular Dysfunction in Type 2 Diabetes Mellitus. Cells, 8.","DOI":"10.3390\/cells8121595"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"34","DOI":"10.3389\/fphar.2015.00034","article-title":"Diabetes Impairs the Vascular Effects of Aldosterone Mediated by G Protein-Coupled Estrogen Receptor Activation","volume":"6","author":"Ferreira","year":"2015","journal-title":"Front. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.ijcard.2014.06.045","article-title":"Dietary Ellagic Acid Improves Oxidant-Induced Endothelial Dysfunction and Atherosclerosis: Role Of Nrf2 Activation","volume":"175","author":"Ding","year":"2014","journal-title":"Int. J. Cardiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"2809","DOI":"10.2337\/db06-1003","article-title":"Activation of Nf-E2-Related Factor-2 Reverses Biochemical Dysfunction of Endothelial Cells Induced by Hyperglycemia Linked to Vascular Disease","volume":"57","author":"Xue","year":"2008","journal-title":"Diabetes"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1161\/HYPERTENSIONAHA.115.06163","article-title":"Downregulation of Nuclear Factor Erythroid 2-Related Factor and Associated Antioxidant Genes Contributes to Redox-Sensitive Vascular Dysfunction in Hypertension","volume":"66","author":"Lopes","year":"2015","journal-title":"Hypertension"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.mrfmmm.2009.09.007","article-title":"A Protective Role of Nuclear Factor-Erythroid 2-Related Factor-2 (Nrf2) in Inflammatory Disorders","volume":"690","author":"Kim","year":"2010","journal-title":"Mutat. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1097\/nen.0b013e31802d6da9","article-title":"Expression of Nrf2 in Neurodegenerative Diseases","volume":"66","author":"Ramsey","year":"2007","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"382","DOI":"10.3389\/fphar.2019.00382","article-title":"Nrf2 as a Potential Mediator of Cardiovascular Risk In Metabolic Diseases","volume":"10","author":"Rodrigues","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"9237263","DOI":"10.1155\/2017\/9237263","article-title":"The Role of Nrf2 In Cardiovascular Function and Disease","volume":"2017","author":"Satta","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1089\/ars.2013.5565","article-title":"Aldosterone Activates Transcription Factor Nrf2 in Kidney Cells both In Vitro and In Vivo","volume":"21","author":"Queisser","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"8804","DOI":"10.1158\/0008-5472.CAN-05-3513","article-title":"Mechanism of Action of Sulforaphane: Inhibition of P38 Mitogen-Activated Protein Kinase Isoforms Contributing to the Induction of Antioxidant Response Element-Mediated Heme Oxygenase-1 in Human Hepatoma Hepg2 Cells","volume":"66","author":"Keum","year":"2006","journal-title":"Cancer Res."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Neves, K.B., Montezano, A.C., Alves-Lopes, R., Bruder-Nascimento, T., Costa, R.M., Costa, R.S., Touyz, R.M., and Tostes, R.C. (2018). Upregulation of Nrf2 and Decreased Redox Signaling Contribute to Renoprotective Effects of Chemerin Receptor Blockade in Diabetic Mice. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19082454"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.bbrc.2019.05.010","article-title":"Curcumin Upregulates the Nrf2 System by Repressing Inflammatory Signaling-Mediated Keap1 Expression in Insulin-Resistant Conditions","volume":"514","author":"Ren","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.bbadis.2011.03.008","article-title":"Resveratrol Protects Diabetic Kidney by Attenuating Hyperglycemia-Mediated Oxidative Stress and Renal Inflammatory Cytokines via Nrf2-Keap1 Signaling","volume":"1812","author":"Palsamy","year":"2011","journal-title":"Biochim. Et Biophys. Acta"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/11\/6154\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:11:45Z","timestamp":1760163105000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/11\/6154"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,7]]},"references-count":52,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,6]]}},"alternative-id":["ijms22116154"],"URL":"https:\/\/doi.org\/10.3390\/ijms22116154","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,7]]}}}