Nephrin loss is reduced by grape seed proanthocyanidins in the experimental diabetic nephropathy rat model

Diabetic nephropathy (DN) is one of the major causes of end-stage renal failure. Grape seed proanthocyanidin extracts (GSPE) are known to act as antioxidants. The current study aimed to determine the effects of GSPE on the streptozotocin (STZ) -induced diabetic rat model and to explore the underlying mechanism of its action. Wistar rats were induced into a diabetic state by injection of STZ and were treated with 250 mg.kg(-1).day(-1) GSPE for 24 weeks. Kidney samples were collected for observation of renal pathological changes by light microscope (periodic acid-Schiff staining) and electron microscopy. Reverse transcription-polymerase chain reaction, western blotting, and immunohistochemical staining were used to detect the mRNA and protein expression of the receptor for advanced glycation end-products (RAGE), nephrin and podocin. The results indicated that diabetic rats treated with GSPE had markedly reduced Ccr, urinary albumin excretion, ratio of kidney weight to body weight, AGEs and ECM accumulation (P< 0.01) compared with that in the diabetic rats. GSPE treatment can also reverse the renal pathological damage in diabetic rats. Further results indicated that GSPE treatment significantly decreased the RAGE expression level (P< 0.01), and significantly increased the expression level of nephrin in the kidney and glomeruli of diabetic rats (P< 0.01). However, no significant differences were identified in the expression of podocin following GSPE treatment (P> 0.05). In conclusion, the results demonstrated that GSPE exerts a reno-protective effect by decreasing urinary albumin excretion and reversing renal pathological damage in diabetic rats. The underlying mechanism of GSPE activity is associated with the decreased expression of the AGEs/RAGE axis and the increased expression of nephrin in diabetic rats.