ArticleFree radical biology & medicine2015
Metallothionein plays a prominent role in the prevention of diabetic nephropathy by sulforaphane via up-regulation of Nrf2.
Article in Free radical biology & medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 92 citations in OpenAlex.
- Compartment-specific Zinc Misallocation in Diabetic Foot Ulcers: Mechanistic Coupling Between Macrophage M1 Locking and MMP-9 Hyperactivation.Biological trace element research · 2026Review
- Interleukin 33 Promotes Liver Sinusoidal Endothelial Cell Dysfunction and Hepatic Fibrosis in Diabetic Mice.Diabetes & metabolism journal · 2025Article
- NRF2 Dysregulation and Therapeutic Insights Across Chronic Kidney Diseases.International journal of molecular sciences · 2025Review
- Ranolazine as a therapeutic agent for diabetic cardiomyopathy: reducing endoplasmic reticulum stress and inflammation in type 2 diabetic rat model.BMC pharmacology & toxicology · 2025Article
- Sulforaphane alleviates renal fibrosis through dual regulation on mTOR-mediated autophagy pathway.International urology and nephrology · 2025Article
- The protection of sulforaphane on subarachnoid hemorrhage-induced intestinal mucosa injury in rats.Frontiers in molecular biosciences · 2025Article
- Exacerbation by knocking-out metallothionein gene of obesity-induced cardiac remodeling is associated with the activation of CARD9 signaling.International journal of biological sciences · 2025Article
- Identification of podocyte molecular markers in diabetic kidney disease via single-cell RNA sequencing and machine learning.PloS one · 2025Article
- Invited Perspective: New Insight into Cadmium-Related Osteoporosis Yields Hope for Prevention and Therapy.Environmental health perspectives · 2024Article
- Insights into the Therapeutic uses of Plant Derive Phytocompounds onDiabetic Nephropathy.Current diabetes reviews · 2024Review
- Oxidative Stress Induced by Lipotoxicity and Renal Hypoxia in Diabetic Kidney Disease and Possible Therapeutic Interventions: Targeting the Lipid Metabolism and Hypoxia.Antioxidants (Basel, Switzerland) · 2023Review
- A mechanistic overview of sulforaphane and its derivatives application in diabetes and its complications.Inflammopharmacology · 2023Review
- Oxidative Stress and NRF2/KEAP1/ARE Pathway in Diabetic Kidney Disease (DKD): New Perspectives.Biomolecules · 2022Review
- Article
- Metals and Metallothionein Expression in Relation to Progression of Chronic Kidney Disease of Unknown Etiology (CKDu) in Sri Lanka.Diseases (Basel, Switzerland) · 2022Article
- Knowledge domain and emerging trends in diabetic cardiomyopathy: A scientometric review based on CiteSpace analysis.Frontiers in cardiovascular medicine · 2022Article
- Sulforaphane Ameliorates Diabetes-Induced Renal Fibrosis through Epigenetic Up-Regulation of BMP-7.Diabetes & metabolism journal · 2021Article
- Nrf2 Activation Attenuates Acrylamide-Induced Neuropathy in Mice.International journal of molecular sciences · 2021Article
- The Influence of Plant Extracts and Phytoconstituents on Antioxidant Enzymes Activity and Gene Expression in the Prevention and Treatment of Impaired Glucose Homeostasis and Diabetes Complications.Antioxidants (Basel, Switzerland) · 2021Review
- Eat Your Broccoli: Oxidative Stress, NRF2, and Sulforaphane in Chronic Kidney Disease.Nutrients · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
Sulforaphane (SFN) prevents diabetic nephropathy (DN) in type 1 diabetes via up-regulation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2). However, it has not been addressed whether SFN also prevents DN from type 2 diabetes or which Nrf2 downstream gene(s) play(s) the key role in SFN renal protection. Here we investigated whether Nrf2 is required for SFN protection against type 2 diabetes-induced DN and whether metallothionein (MT) is an Nrf2 downstream antioxidant using Nrf2 knockout (Nrf2-null) mice. In addition, MT knockout mice were used to further verify if MT is indispensable for SFN protection against DN. Diabetes-increased albuminuria, renal fibrosis, and inflammation were significantly prevented by SFN, and Nrf2 and MT expression was increased. However, SFN renal protection was completely lost in Nrf2-null diabetic mice, confirming the pivotal role of Nrf2 in SFN protection from type 2 diabetes-induced DN. Moreover, SFN failed to up-regulate MT in the absence of Nrf2, suggesting that MT is an Nrf2 downstream antioxidant. MT deletion resulted in a partial, but significant attenuation of SFN renal protection from type 2 diabetes, demonstrating a partial requirement for MT for SFN renal protection. Therefore, the present study demonstrates for the first time that as an Nrf2 downstream antioxidant, MT plays an important, though partial, role in mediating SFN renal protection from type 2 diabetes.
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