ArticleScientific reports2019
AKF-PD alleviates diabetic nephropathy via blocking the RAGE/AGEs/NOX and PKC/NOX Pathways.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- Ferroptosis in prostatitis: pathogenic mechanisms and therapeutic advances.Molecular and cellular biochemistry · 2026Review
- Investigating the Effects and Potential Mechanisms of Astragalus Root Against Diabetic Nephropathy Based on Bioinformatics Analysis and In Vitro Validation.International journal of molecular sciences · 2026Article
- Advances in Targeting the AGEs-RAGE Pathway for the Treatment of Diabetic Kidney Disease.Drug design, development and therapy · 2026Review
- Nrf2-Mediated Ferroptosis Is Involved in Berberine-Induced Alleviation of Diabetic Kidney Disease.Phytotherapy research : PTR · 2025Article
- Inflammation, Apoptosis, and Fibrosis in Diabetic Nephropathy: Molecular Crosstalk in Proximal Tubular Epithelial Cells and Therapeutic Implications.Current issues in molecular biology · 2025Review
- Regulation of pyroptosis in diabetic nephropathy by long non-coding and circular RNAs.Clinical and experimental medicine · 2025Review
- Mitochondrial dysfunction in diabetic ulcers: pathophysiological mechanisms and targeted therapeutic strategies.Frontiers in cell and developmental biology · 2025Review
- Diabetic Kidney Disease: Disease Progression Driven by Positive Feedback Loops and Therapeutic Strategies Targeting Pathogenic Pathways.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Review
- Sodium butyrate enhances titanium nail osseointegration in ovariectomized rats by inhibiting the PKCα/NOX4/ROS/NF-κB pathways.Journal of orthopaedic surgery and research · 2023Article
- Nox4 as a novel therapeutic target for diabetic vascular complications.Redox biology · 2023Review
- Frontiers in Understanding the Pathological Mechanism of Diabetic Retinopathy.Medical science monitor : international medical journal of experimental and clinical research · 2023Review
- Diabetic vascular diseases: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2023Review
- Echinochrome A Prevents Diabetic Nephropathy by Inhibiting the PKC-Iota Pathway and Enhancing Renal Mitochondrial Function in db/db Mice.Marine drugs · 2023Article
- Oxidative stress and inflammation in diabetic nephropathy: role of polyphenols.Frontiers in immunology · 2023Review
- The impact of oxidative stress-induced mitochondrial dysfunction on diabetic microvascular complications.Frontiers in endocrinology · 2023Review
- Structural and Functional Changes in Aging Kidneys.International journal of molecular sciences · 2022Review
- Diabetic Kidney Disease: From Pathogenesis to Novel Treatment Possibilities.Handbook of experimental pharmacology · 2022Review
- Verbascoside Protects Gingival Cells against High Glucose-Induced Oxidative Stress via PKC/HMGB1/RAGE/NFκB Pathway.Antioxidants (Basel, Switzerland) · 2021Article
- Organelle stress and glycation in kidney disease.Glycoconjugate journal · 2021Review
- Article
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diabetic nephropathy (DN) is a major complication of diabetes. Currently, drugs are not available to effectively control the disease. Fluorofenidone (AKF-PD) is a recently developed drug; it possesses activities in reducing DN progression in preclinical research. Nonetheless, its renal protection and the underlying mechanisms have not been thoroughly investigated. We report here that AKF-PD significantly alleviatesrenal oxidative stress (OS) in db/dbmice through downregulation of Nicotinamide Adenine Dinucleotide Phosphate (NADPH) oxidase and upregulation of glutathione peroxidase and superoxide dismutase, thereby protecting kidney from DN pathogenesis. AKF-PD likely reduces OS through the advanced glycation end products (AGE) and protein kinase C (PKC) pathways. While renal AGEs, PKCα, PKCβ, and NADPH oxidase 4 (NOX4) were all substantially upregulated in db/db mice compared to db/m animals, AKF-PD robustly downregulated all these events to the basal levelsdetected in db/m mice. In primary human renal mesangial cells (HMCs), high glucose (HG) elevated receptor for advanced glycation endproducts (RAGE), PKCα, PKCβ and NOX4 activity, and induced the production of reactive oxygen species (ROS); these events were all inhibited by AKF-PD. Furthermore, HG led to mitochondrial damagein HMCs;AKF-PD conferred protection on the damage. Knockdown of either PKCα or PKCβ reduced HG-induced ROS production and mitochondrial damage in HMCs. The knockdown significantly enhanced AKF-PD-mediated inhibition of ROS production and mitochondrial damage in HG-treated HMCs. Collectively, our study demonstrates that AKF-PD protects renal function under diabetes conditions in part through inhibition of OS during DN pathogenesis. AKF-PD can be explored for clinical applications in DN therapy.
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