Oxidative Stress and NRF2/KEAP1/ARE Pathway in Diabetic Kidney Disease (DKD): New Perspectives
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 patie...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-09-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/9/1227 |
| _version_ | 1827663021663584256 |
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| author | Daniela Maria Tanase Evelina Maria Gosav Madalina Ioana Anton Mariana Floria Petronela Nicoleta Seritean Isac Loredana Liliana Hurjui Claudia Cristina Tarniceriu Claudia Florida Costea Manuela Ciocoiu Ciprian Rezus |
| author_facet | Daniela Maria Tanase Evelina Maria Gosav Madalina Ioana Anton Mariana Floria Petronela Nicoleta Seritean Isac Loredana Liliana Hurjui Claudia Cristina Tarniceriu Claudia Florida Costea Manuela Ciocoiu Ciprian Rezus |
| author_sort | Daniela Maria Tanase |
| collection | DOAJ |
| description | 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-α, TGF-β, NF-κB, 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. |
| first_indexed | 2024-03-10T00:37:02Z |
| format | Article |
| id | doaj.art-1f63dd1bd40e48e88a5a37a4c62c9ef1 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T00:37:02Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-1f63dd1bd40e48e88a5a37a4c62c9ef12023-11-23T15:15:01ZengMDPI AGBiomolecules2218-273X2022-09-01129122710.3390/biom12091227Oxidative Stress and NRF2/KEAP1/ARE Pathway in Diabetic Kidney Disease (DKD): New PerspectivesDaniela Maria Tanase0Evelina Maria Gosav1Madalina Ioana Anton2Mariana Floria3Petronela Nicoleta Seritean Isac4Loredana Liliana Hurjui5Claudia Cristina Tarniceriu6Claudia Florida Costea7Manuela Ciocoiu8Ciprian Rezus9Department of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, RomaniaDepartment of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, RomaniaDepartment of Rheumatology and Physiotherapy, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, RomaniaDepartment of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, RomaniaDepartment of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, RomaniaDepartment of Morpho-Functional Sciences II, Physiology Discipline, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, RomaniaDepartment of Morpho-Functional Sciences I, Discipline of Anatomy, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, RomaniaDepartment of Ophthalmology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, RomaniaDepartment of Pathophysiology, Faculty of Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, RomaniaDepartment of Internal Medicine, “Grigore T. Popa” University of Medicine and Pharmacy, 700115 Iasi, RomaniaDiabetes 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-α, TGF-β, NF-κB, 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.https://www.mdpi.com/2218-273X/12/9/1227oxidative stressNRF2/KEAP1/ARE pathwaydiabetic nephropathydiabetes mellitusantioxidant therapydiabetic kidney disease |
| spellingShingle | Daniela Maria Tanase Evelina Maria Gosav Madalina Ioana Anton Mariana Floria Petronela Nicoleta Seritean Isac Loredana Liliana Hurjui Claudia Cristina Tarniceriu Claudia Florida Costea Manuela Ciocoiu Ciprian Rezus Oxidative Stress and NRF2/KEAP1/ARE Pathway in Diabetic Kidney Disease (DKD): New Perspectives Biomolecules oxidative stress NRF2/KEAP1/ARE pathway diabetic nephropathy diabetes mellitus antioxidant therapy diabetic kidney disease |
| title | Oxidative Stress and NRF2/KEAP1/ARE Pathway in Diabetic Kidney Disease (DKD): New Perspectives |
| title_full | Oxidative Stress and NRF2/KEAP1/ARE Pathway in Diabetic Kidney Disease (DKD): New Perspectives |
| title_fullStr | Oxidative Stress and NRF2/KEAP1/ARE Pathway in Diabetic Kidney Disease (DKD): New Perspectives |
| title_full_unstemmed | Oxidative Stress and NRF2/KEAP1/ARE Pathway in Diabetic Kidney Disease (DKD): New Perspectives |
| title_short | Oxidative Stress and NRF2/KEAP1/ARE Pathway in Diabetic Kidney Disease (DKD): New Perspectives |
| title_sort | oxidative stress and nrf2 keap1 are pathway in diabetic kidney disease dkd new perspectives |
| topic | oxidative stress NRF2/KEAP1/ARE pathway diabetic nephropathy diabetes mellitus antioxidant therapy diabetic kidney disease |
| url | https://www.mdpi.com/2218-273X/12/9/1227 |
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