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Abstract: FR-PO613

Quercetin Ameliorates Podocyte Injury by Inhibiting the ERK Signaling Pathway in Rats with Diabetic Nephropathy

Session Information

Category: Diabetes

  • 501 Diabetes Mellitus and Obesity: Basic - Experimental

Authors

  • Gao, Fanfan, Dialysis Centure of First Affiliated Hospital of Medicine School, Xi'an Jiaotong University, Xi'an, China
  • Jiang, Hongli, Dialysis Centure of First Affiliated Hospital of Medicine School, Xi'an Jiaotong University, Xi'an, China
Background

An increasing number of investigations revealed that podocytes play a crucial role in the development and progression of diabetic nephropathy (DN). Quercetin, an antioxidant, may be a potential alternative to ameliorate podocyte injury in DN rats. The aim of this study was to investigate the protective effect and underlying mechanism of quercetin on podocyte injury in rats with diabetic nephropathy.

Methods

SD rats (180-200g) were randomly divided into four groups: normal control (NC, n=10), diabetic nephropathy (DN, n=10), DN treated with low-dose quercetin (DN+LQ, n=10) and DN treated with high-dose quercetin (DN+HQ, n=10). Diabetic nephropathy was induced by intraperitoneal injections of streptozotocin(STZ) (60mg/kg). DN+LQ rats were treated with 50mg/kg/d quercetin by gavage, DN+HQ rats were treated with 100mg/kg/d quercetin by gavage, NC and DN rats were treated with 100mg/kg/d DMSO by gavage. Blood glucose and body weight were obtained every two weeks, microalbuminuria and urine creatinine were obtained every four weeks. All animals were sacrificed after 12 weeks of treatments.

Results

In the present study, the levels of blood glucose, kidney hypertrophy index, microalbuminuria, SCr, BUN, TG were markedly increased in rats with STZ injection compared with NC rats, expectedly, these alterations were less intense in animals treated with quercetin. The picture of electron microscope showed foot process fusion in DN rats, while quercetin markedly inhibited foot process infusion. Immunohistochemical and western blotting results showed that the expression of nephrin and podocin in DN rats was significantly decreased, the expression of desmin, ERK, p-ERK in DN rats was significantly increased, whereas quercetin reversed these above changes. Additionally, the contents of nephrin and podocin in urine of DN rats were markedly higher than that of NC rats, while the contents of GSH and SOD in serum and kidney tissue of DN rats were significantly lower than that of NC rats. However, quercetin decreased the contents of nephrin and podocin in urine and increased the contents of SOD and GSH in blood and kidney tissue.

Conclusion

Quercetin treatment effectively ameliorated podocyte injury in rats with DN by inhibiting ERK signaling pathway. The manipulation of quercetin might act as a promising therapeutic intervention for diabetic nephropathy.