{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T21:48:19Z","timestamp":1793051299707,"version":"4.5.0"},"reference-count":190,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T00:00:00Z","timestamp":1662076800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Diabetes mellitus (DM) is one of the most debilitating chronic diseases worldwide, with increased prevalence and incidence. In addition to its macrovascular damage, through its microvascular complications, such as Diabetic Kidney Disease (DKD), DM further compounds the quality of life of these patients. Considering DKD is the main cause of end-stage renal disease (ESRD) in developed countries, extensive research is currently investigating the matrix of DKD pathophysiology. Hyperglycemia, inflammation and oxidative stress (OS) are the main mechanisms behind this disease. By generating pro-inflammatory factors (e.g., IL-1,6,18, TNF-\u03b1, TGF-\u03b2, NF-\u03baB, MCP-1, VCAM-1, ICAM-1) and the activation of diverse pathways (e.g., PKC, ROCK, AGE\/RAGE, JAK-STAT), they promote a pro-oxidant state with impairment of the antioxidant system (NRF2\/KEAP1\/ARE pathway) and, finally, alterations in the renal filtration unit. Hitherto, a wide spectrum of pre-clinical and clinical studies shows the beneficial use of NRF2-inducing strategies, such as NRF2 activators (e.g., Bardoxolone methyl, Curcumin, Sulforaphane and their analogues), and other natural compounds with antioxidant properties in DKD treatment. However, limitations regarding the lack of larger clinical trials, solubility or delivery hamper their implementation for clinical use. Therefore, in this review, we will discuss DKD mechanisms, especially oxidative stress (OS) and NRF2\/KEAP1\/ARE involvement, while highlighting the potential of therapeutic approaches that target DKD via OS.<\/jats:p>","DOI":"10.3390\/biom12091227","type":"journal-article","created":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T20:48:25Z","timestamp":1662410905000},"page":"1227","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":197,"title":["Oxidative Stress and NRF2\/KEAP1\/ARE Pathway in Diabetic Kidney Disease (DKD): New Perspectives"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7144-2506","authenticated-orcid":false,"given":"Daniela Maria","family":"Tanase","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Internal Medicine Clinic, \u201cSf. Spiridon\u201d County Clinical Emergency Hospital Iasi, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1730-9306","authenticated-orcid":false,"given":"Evelina Maria","family":"Gosav","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Internal Medicine Clinic, \u201cSf. Spiridon\u201d County Clinical Emergency Hospital Iasi, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3626-6201","authenticated-orcid":false,"given":"Madalina Ioana","family":"Anton","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Physiotherapy, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"I Rheumatology Clinic, Clinical Rehabilitation Hospital, 700661 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9465-1503","authenticated-orcid":false,"given":"Mariana","family":"Floria","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Internal Medicine Clinic, \u201cSf. Spiridon\u201d County Clinical Emergency Hospital Iasi, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petronela Nicoleta","family":"Seritean Isac","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Internal Medicine Clinic, \u201cSf. Spiridon\u201d County Clinical Emergency Hospital Iasi, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3803-9405","authenticated-orcid":false,"given":"Loredana Liliana","family":"Hurjui","sequence":"additional","affiliation":[{"name":"Department of Morpho-Functional Sciences II, Physiology Discipline, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Hematology Laboratory, \u201cSt. Spiridon\u201d County Clinical Emergency Hospital, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia Cristina","family":"Tarniceriu","sequence":"additional","affiliation":[{"name":"Department of Morpho-Functional Sciences I, Discipline of Anatomy, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Hematology Clinic, \u201cSf. Spiridon\u201d County Clinical Emergency Hospital, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia Florida","family":"Costea","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"2nd Ophthalmology Clinic, \u201cProf. Dr. Nicolae Oblu\u201d Emergency Clinical Hospital, 700309 Ia\u0219i, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Ciocoiu","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, Faculty of Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1155-7325","authenticated-orcid":false,"given":"Ciprian","family":"Rezus","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, \u201cGrigore T. Popa\u201d University of Medicine and Pharmacy, 700115 Iasi, Romania"},{"name":"Internal Medicine Clinic, \u201cSf. Spiridon\u201d County Clinical Emergency Hospital Iasi, 700111 Iasi, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,2]]},"reference":[{"key":"ref_1","first-page":"7865359","article-title":"Oleander Stem and Root Standardized Extracts Mitigate Acute Hyperglycaemia by Limiting Systemic Oxidative Stress Response in Diabetic Mice","volume":"2019","author":"Dey","year":"2019","journal-title":"Adv. Pharmacol. Sci."},{"key":"ref_2","unstructured":"(2022, August 01). 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