Background: Diabetic nephropathy (DN) is the most common cause of end-stage renal failure. Grape seed proanthocyanidin extracts (GSPEs) are powerful antioxidants. However, the role of GSPEs in advanced glycation end products (AGEs), expression of connective tissue growth factor (CTGF) and bone morphogenetic protein-7 (BMP-7) in DN has not been elucidated. Using streptozotocin-induced diabetic rats, we evaluated the effects of GSPE in DN.
Methods: Wistar rats were induced into diabetes using streptozotocin injections, and diabetic rats were treated with GSPE (high dosage: 500 mg/kg per day; low dosage: 250 mg/kg.per day) for 24 weeks. The renal pathologic changes were examined with periodic acid-Schiff (PAS) staining under an electron microscope. The mRNA and protein expressions of CTGF and BMP-7 in kidney were detected by RT-PCR and immunohistochemical staining.
Results: Treated animals showed a reduction in serum AGEs (p<0.01), proteinuria (p<0.01) and systolic blood pressure (SBP) (p<0.01). GSPE reduced the expression of mRNA and protein of CTGF in the kidney (p<0.05 and p<0.01), which were contributing to reversal of extracellular matrix (ECM) accumulation in DN. GSPE increased the expression of mRNA and protein of BMP-7 in the kidney (p<0.05 and p<0.01), which were contributing to improvement of the microstructure of podocytes and ECM accumulation in DN.
Conclusion: Our results suggest that GSPEs hold substantial promise for the treatment of DN. GSPEs can decrease proteinuria and attenuate the progression of nephropathy in diabetic rats. Renoprotective effects of GSPE correlated with suppression of AGEs, down-regulating expression of CTGF and up-regulating the expression of BMP-7.