Quercetin Ameliorates Diabetic Kidney Injury by Inhibiting Ferroptosis via Activating Nrf2/HO-1 Signaling Pathway

Area of Science:

• Nephrology
• Cell Biology
• Biochemistry

Background:

• Diabetic nephropathy (DN) is a leading cause of end-stage renal disease with complex pathogenesis and limited treatment options.
• Ferroptosis, an iron-dependent cell death, contributes to renal tubular injury in DN, suggesting that inhibiting ferroptosis may be a therapeutic strategy.
• Quercetin (QCT), a natural flavonoid, has shown potential in ameliorating DN, but its protective mechanisms remain unclear.

Purpose of the Study:

• To investigate the antiferroptotic effect of Quercetin (QCT) in diabetic nephropathy (DN).
• To elucidate the underlying nephroprotective mechanism of QCT involving ferroptosis regulation and signaling pathways.

Main Methods:

• Utilized a mouse model of DN and high glucose (HG)-incubated renal tubular epithelial cells (HK-2) to study ferroptosis.
• Assessed the expression of key ferroptosis-related proteins, including transferrin receptor 1 (TFR-1), glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH-1), and solute carrier family 7 member 11 (SLC7A11).
• Investigated the activation of the NFE2-related factor 2 (Nrf2)/Heme oxygenase-1 (HO-1) signaling pathway in response to QCT treatment.

Main Results:

• High glucose induced ferroptosis in renal tubular epithelial cells.
• QCT treatment inhibited ferroptosis by downregulating TFR-1 and upregulating GPX4, FTH-1, and SLC7A11 expression.
• QCT activated the Nrf2/HO-1 signaling pathway, increasing Nrf2 and HO-1 levels both in vitro and in vivo.

Conclusions:

• Quercetin (QCT) exerts a nephroprotective effect in diabetic nephropathy (DN) by inhibiting ferroptosis in renal tubular epithelial cells.
• The mechanism involves the regulation of ferroptosis markers and activation of the Nrf2/HO-1 signaling pathway.
• QCT represents a promising therapeutic agent for DN, offering a novel approach by targeting ferroptosis.