Quercetin improves diabetic kidney disease by inhibiting ferroptosis and regulating the Nrf2 in streptozotocin-induced diabetic rats

• Published in: Renal failure 2024-12, Vol.46 (1), p.2327495-2327495
• Main Authors: Zhang, Lei, Wang, Xingzhi, Chang, Liang, Ren, Yiqun, Sui, Manshu, Fu, Yuting, Hao, Lirong
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Basic Sciences Investigations; Cell activation; Cell culture; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - metabolism; Diabetic kidney disease (DKD); Diabetic Nephropathies - drug therapy; Diabetic Nephropathies - etiology; Diabetic Nephropathies - metabolism; End-stage renal disease; Epithelial cells; Ferroptosis; Flavonoids; Kidney diseases; Mice; NF-E2-Related Factor 2 - metabolism; Nrf2; Quercetin; Quercetin - pharmacology; Quercetin - therapeutic use; rat; Rats; Streptozocin; streptozotocin
• ISSN: 0886-022X; 1525-6049
• DOI: 10.1080/0886022X.2024.2327495

Diabetic kidney disease (DKD) is a leading factor in end-stage renal disease. The complexity of its pathogenesis, combined with the limited treatment efficacy, necessitates deeper insights into potential causes. Studies suggest that ferroptosis-driven renal tubular damage contributes to DKD's progression, making its counteraction a potential therapeutic strategy. Quercetin, a flavonoid found in numerous fruits and vegetables, has demonstrated DKD mitigation in mouse models, though its protective mechanism remains ambiguous. In this study, we delved into quercetin's potential anti-ferroptotic properties, employing a DKD rat model and high glucose (HG)-treated renal tubular epithelial cell models. Our findings revealed that HG prompted unusual ferroptosis activation in renal tubular epithelial cells. However, quercetin counteracted this by inhibiting ferroptosis and activating NFE2-related factor 2 (Nrf2) expression in both DKD rats and HG-treated HK-2 cells, indicating its renal protective role. Further experiments, both and , validated that quercetin stimulates Nrf2. Thus, our research underscores quercetin's potential in DKD treatment by modulating the ferroptosis process activating Nrf2 in a distinct DKD rat model, offering a fresh perspective on quercetin's protective mechanisms.