ArticleJournal of diabetes investigation2019
Canagliflozin, a sodium-glucose cotransporter 2 inhibitor, normalizes renal susceptibility to type 1 cardiorenal syndrome through reduction of renal oxidative stress in diabetic rats.
Article in Journal of diabetes investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 of them syntheses that pooled it.
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Who cites it
33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 57 citations in OpenAlex.
- GV effects of diabetes mellitus on clinical outcomes of patients with acute heart failure: A systematic review and meta-analysis.PloS one · 2025Pooled it
- Role and mechanisms of SGLT-2 inhibitors in the treatment of diabetic kidney disease.Frontiers in immunology · 2023Pooled it
- Antioxidant Effects of SGLT2 Inhibitors on Cardiovascular-Kidney-Metabolic (CKM) Syndrome.Antioxidants (Basel, Switzerland) · 2025Review
- Sodium-Glucose Cotransporter 2 Inhibitors as Potential Antioxidant Therapeutic Agents in Cardiovascular and Renal Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Quantitative Proteomics Combined with Network Pharmacology Analysis Unveils the Biological Basis of Schisandrin B in Treating Diabetic Nephropathy.Combinatorial chemistry & high throughput screening · 2024Article
- Antioxidant and Anti-Inflammatory Functions of High-Density Lipoprotein in Type 1 and Type 2 Diabetes.Antioxidants (Basel, Switzerland) · 2023Review
- Sodium Glucose Transporter-2 Inhibitors (SGLT2Is)-TLRs Axis Modulates Diabetes.Cell biochemistry and biophysics · 2023Review
- Toll-like receptors 2 and 4 stress signaling and sodium-glucose cotransporter-2 in kidney disease.Molecular and cellular biochemistry · 2023Review
- SGLT2 Inhibitors in the Treatment of Diabetic Kidney Disease: More than Just Glucose Regulation.Pharmaceutics · 2023Review
- Novel Antidiabetic Agents and Their Effects on Lipid Profile: A Single Shot for Several Cardiovascular Targets.International journal of molecular sciences · 2023Review
- Early diabetic kidney disease: Focus on the glycocalyx.World journal of diabetes · 2023Review
- Acute Cardiorenal Syndrome: Epidemiology, Pathophysiology, Assessment, and Treatment.Reviews in cardiovascular medicine · 2023Review
- Mechanistic View on the Effects of SGLT2 Inhibitors on Lipid Metabolism in Diabetic Milieu.Journal of clinical medicine · 2022Review
- Oxidative Stress Management in Cardiorenal Diseases: Focus on Novel Antidiabetic Agents, Finerenone, and Melatonin.Life (Basel, Switzerland) · 2022Review
- Experimental models of acute kidney injury for translational research.Nature reviews. Nephrology · 2022Review
- Sodium-glucose cotransporter-2 inhibitor alleviated atrial remodeling in STZ-induced diabetic rats by targeting TLR4 pathway.Frontiers in cardiovascular medicine · 2022Article
- Renal outcomes with sodium-glucose cotransporters 2 inhibitors.Frontiers in endocrinology · 2022Review
- Markers of Kidney Injury, Inflammation, and Fibrosis Associated With Ertugliflozin in Patients With CKD and Diabetes.Kidney international reports · 2021Article
- Canagliflozin protects against sepsis capillary leak syndrome by activating endothelial α1AMPK.Scientific reports · 2021Article
- Involvement of necroptosis in contrast-induced nephropathy in a rat CKD model.Clinical and experimental nephrology · 2021Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
AIMS/
introductionType 2 diabetes mellitus is a risk factor of acute kidney injury after myocardial infarction (MI), a form of cardiorenal syndrome. Recent clinical trials have shown that a sodium-glucose cotransporter 2 (SGLT2) inhibitor improved both cardiac and renal outcomes in patients with type 2 diabetes mellitus, but effects of an SGLT2 inhibitor on cardiorenal syndrome remain unclear. MATERIALS AND
methodsType 2 diabetes mellitus (Otsuka Long-Evans Tokushima Fatty rats [OLETF]) and control (Long-Evans Tokushima Otsuka rats [LETO]) were treated with canagliflozin, an SGLT2 inhibitor, for 2 weeks. Renal tissues were analyzed at 12 h after MI with or without preoperative fasting.
resultsCanagliflozin reduced blood glucose levels in OLETF, and blood β-hydroxybutyrate levels were increased by canagliflozin only with fasting. MI increased neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 protein levels in the kidney by 3.2- and 1.6-fold, respectively, in OLETF, but not in LETO. The renal messenger ribonucleic acid level of Toll-like receptor 4 was higher in OLETF than in LETO after MI, whereas messenger ribonucleic acid levels of cytokines/chemokines were not significantly different. Levels of lipid peroxides, nicotinamide adenine dinucleotide phosphate oxidase (NOX)2 and NOX4 proteins after MI were significantly higher in OLETF than in LETO. Canagliflozin with pre-MI fasting suppressed MI-induced renal expression of neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 in OLETF, together with reductions in lipid peroxides and NOX proteins in the kidney. Blood β-hydroxybutyrate levels before MI were inversely correlated with neutrophil gelatinase-associated lipocalin protein levels in OLETF. Pre-incubation with β-hydroxybutyrate attenuated angiotensin II-induced upregulation of NOX4 in NRK-52E cells.
conclusionsThe findings suggest that SGLT2 inhibitor treatment with a fasting period protects kidneys from MI-induced cardiorenal syndrome, possibly by β-hydroxybutyrate-mediated reduction of NOXs and oxidative stress, in type 2 diabetic rats.
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