ArticleInternational journal of molecular sciences2019
Xanthine Oxidase Inhibitor Febuxostat Exerts an Anti-Inflammatory Action and Protects against Diabetic Nephropathy Development in KK-Ay Obese Diabetic Mice.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 41 citations in OpenAlex.
- Evaluation of febuxostat in treating diabetic kidney disease with hyperuricemia: a systematic review and meta-analysis of randomized controlled trials.Frontiers in medicine · 2025Pooled it
- Febuxostat provides renoprotection in patients with hyperuricemia or gout: a systematic review and meta-analysis of randomized controlled trials.Annals of medicine · 2024Pooled it
- Effect of the Xanthine Oxidase Inhibitor, Febuxostat, on WBC Count in Asymptomatic Hyperuricemia: Subanalysis of the Randomized PRIZE Study.Journal of atherosclerosis and thrombosis · 2024Trial
- Effect of febuxostat on the level of malondialdehyde-modified low-density lipoprotein, an oxidative stress marker: A subanalysis of the PRIZE study.Clinical cardiology · 2023Trial
- Oxidative-Inflammatory Crosstalk and Multi-Target Natural Agents: Decoding Diabetic Vascular Complications.Current issues in molecular biology · 2025Review
- Glomerular Haematopoietic Prostaglandin D Synthase-Prostaglandin D2 Axis Contributes to the Periodontitis-Related Exacerbation of Diabetic Nephropathy in KK-AJournal of clinical periodontology · 2025Article
- Serum Uric Acid Is Associated with Insulin Resistance in Non-Diabetic Subjects.Journal of clinical medicine · 2025Article
- Hyperuricemia-induced complications: dysfunctional macrophages serve as a potential bridge.Frontiers in immunology · 2025Review
- Febuxostat Improves Postprandial Glucose Regulation and Insulin Sensitivity in Hyperuricemic Individuals with Prediabetes or Newly Diagnosed Type 2 Diabetes: A Prospective Cohort Study.Drug design, development and therapy · 2025Article
- Emerging Roles of Xanthine Oxidoreductase in Chronic Kidney Disease.Antioxidants (Basel, Switzerland) · 2024Review
- Febuxostat attenuates secondary brain injury caused by cerebral hemorrhage through inhibiting inflammatory pathways.Iranian journal of basic medical sciences · 2024Article
- Carbonylated Proteins as Key Regulators in the Progression of Metabolic Syndrome.Antioxidants (Basel, Switzerland) · 2023Article
- Oral Administration of Lipopolysaccharide Enhances Insulin Signaling-Related Factors in the KK/Ay Mouse Model of Type 2 Diabetes Mellitus.International journal of molecular sciences · 2023Article
- Inhibition of Xanthine Oxidase Protects against Diabetic Kidney Disease through the Amelioration of Oxidative Stress via VEGF/VEGFR Axis and NOX-FoxO3a-eNOS Signaling Pathway.International journal of molecular sciences · 2023Article
- The Management of Diabetes with Hyperuricemia: Can We Hit Two Birds with One Stone?Journal of inflammation research · 2023Review
- The effects of compound centella formula on OxInflammation and silent information regulator 1 in a high-fat diet/streptozotocin-induced diabetic kidney disease rat model.Experimental and therapeutic medicine · 2021Article
- Article
- The Role of Oxidative Stress in Hyperuricemia and Xanthine Oxidoreductase (XOR) Inhibitors.Oxidative medicine and cellular longevity · 2021Review
- The Crucial Role of Xanthine Oxidase in CKD Progression Associated with Hypercholesterolemia.International journal of molecular sciences · 2020Article
- Regulation of Vascular Function and Inflammation via Cross Talk of Reactive Oxygen and Nitrogen Species from Mitochondria or NADPH Oxidase-Implications for Diabetes Progression.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 2 countries.
Funding
Abstract
Hyperuricemia has been recognized as a risk factor for insulin resistance as well as one of the factors leading to diabetic kidney disease (DKD). Since DKD is the most common cause of end-stage renal disease, we investigated whether febuxostat, a xanthine oxidase (XO) inhibitor, exerts a protective effect against the development of DKD. We used KK-Ay mice, an established obese diabetic rodent model. Eight-week-old KK-Ay mice were provided drinking water with or without febuxostat (15 μg/mL) for 12 weeks and then subjected to experimentation. Urine albumin secretion and degrees of glomerular injury judged by microscopic observations were markedly higher in KK-Ay than in control lean mice. These elevations were significantly normalized by febuxostat treatment. On the other hand, body weights and high serum glucose concentrations and glycated albumin levels of KK-Ay mice were not affected by febuxostat treatment, despite glucose tolerance and insulin tolerance tests having revealed febuxostat significantly improved insulin sensitivity and glucose tolerance. Interestingly, the IL-1β, IL-6, MCP-1, and ICAM-1 mRNA levels, which were increased in KK-Ay mouse kidneys as compared with normal controls, were suppressed by febuxostat administration. These data indicate a protective effect of XO inhibitors against the development of DKD, and the underlying mechanism likely involves inflammation suppression which is independent of hyperglycemia amelioration.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.