Abstract: FR-PO381
Quercetin Ameliorates Podocytes Injury via Inhibition of Oxidative Stress and TGF-β1/Smad Pathway in DN Rats
Session Information
- Diabetic Kidney Disease: Basic - II
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Authors
- Gao, Fanfan, The First Affiliated Hospital of Xi’an Jiaotong University, Xi'an, Shaanxi, China
- Jiang, Hongli, First Affiliated Hospital of Medicine School, Xi?an Jiaotong University, Xi?an, China
Group or Team Name
- Dialysis Department of Nephrology Hospital, First Affiliated Hospital of Medicine School, Xi’an Jiaotong University, Xi’an 710061, Shaanxi, China
Background
An increasing number of investigations revealed that podocytes play a crucial role in the development and progression of diabetic nephropathy (DN). The bioflavonoid quercetin, an antioxidant, may be a potential alternative to ameliorate podocytes 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 (180-220g) were randomly divided into four groups: normal control (NC), diabetic nephropathy (DN), DN treated with low-dose quercetin (DN+LQ) and DN treated with high-dose quercetin (DN+HQ). All diabetic rats were induced by a single intraperitoneal injection of streptozotocin at concentration 60 mg/kg, and quercetin was administered daily with an oral dose of 50 mg/kg (DN+LQ) or 100 mg/kg (DN+HQ) 1 week after STZ injection, NC and DN rats were administered vehicle only. Blood glucose and body weight were measured every 2 weeks, and albuminuria was measured every 4 weeks. All animals were sacrificed after 12 weeks of treatments. Then HE, PAS staining and electron microscope were performed to observe kidney tissue and podocytes. Immunohistochemical stainig and western blotting were performed to explore the expression of podocin, nephrin, desmin, TGF-β1, p-Smad2, and p-Smad3 and Smad7. The contents of SOD, GSH and MDA were examined by ELISA.
Results
In the present study, quercetin markedly decreased blood glucose levels, kidney-to-body weight ratio, albuminuria, creatinine clearance rate, blood urea nitrogen, triglycerides and significantly attenuated oxidative stress compared with the DN group. Moreover, quercetin was observed to inhibit podocyte effacement and decrease the thickness of glomerular basement membranes. Mechanistically, quercetin significantly increased the expression of podocyte-specific markers nephrin and podocin and decreased expression of the podocyte injury marker desmin in DN rats. Quercetin also inhibited activation of the TGF-β1/Smad signaling pathway in DN rats by decreasing expression of TGF-β1, p-Smad2, and p-Smad3, and increasing Smad7 expression.
Conclusion
Quercetin administration ameliorated podocytes injury in DN rats, possibly by inhibiting oxidative stress and the TGF-β1/Smad signaling pathway. Thus, quercetin may be manipulated to act as a potential drug for prevention of early diabetic nephropathy.
Funding
- Government Support - Non-U.S.