Grape Seed Proanthocyanidins Ameliorate Diabetic Nephropathy via Modulation of Levels of AGE, RAGE and CTGF

BACKGROUND: Diabetic nephropathy (DN) is the most common cause of end-stage renal failure. Grape seed proanthocyanidin extracts (GSPE) are powerful antioxidants. However, the role of GSPE on advanced glycation end products (AGEs), receptor for advanced glycation end products (RAGE) and expression of connective tissue growth factor (CTGF) 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 (dosage: 500 mg x kg(-1) x day(-1)) for 24 weeks. The renal pathological changes were examined with PAS staining and electron microscope. The mRNA and protein expression of RAGE and CTGF in kidney were detected by RT-PCR, Western blot and immunohistochemical staining. RESULTS: Treated animals showed reduction in serum AGEs (p < 0.01), proteinuria (p < 0.01) and systolic blood pressure (p < 0.01). GSPE reduced the expression of RAGE (p < 0.01) and CTGF (p < 0.01) in the kidney, which were contributing to reversal of extracellular matrix accumulation in DN. CONCLUSION: Our results suggest that GSPE hold substantial promise for the treatment of DN. GSPE can decrease proteinuria, attenuating the progression of nephropathy in diabetic rats. Renoprotective effects of GSPE are correlated with suppression on AGEs/RAGE axis, downregulating expression of CTGF.