Back‐regulation of six oxidative stress proteins with grape seed proanthocyanidin extracts in rat diabetic nephropathy

Abstract

Diabetic nephropathy (DN) is a major cause of morbidity and mortality in diabetic patients. To prevent the development of this disease and to improve advanced kidney injury, effective therapies directed toward the key molecular target are required. Grape seed proanthocyanidin extracts (GSPE) have been reported to be effective in treating DN, while little is known about the functional protein changes. In this study, we used streptozotocin (STZ) to induce diabetic rats. GSPE (250 mg/kg body weight/day) were administrated to diabetic rats for 24 weeks. Serum glucose, glycated hemoglobin, and advanced glycation end products were determined. Consequently, 2-D difference gel electrophoresis and mass spectrometry were used to investigate kidney protein profiles among the control, untreated and GSPE treated diabetic rats. Twenty-five proteins were found either up-regulated or down-regulated in the kidneys of untreated diabetic rats. Only nine proteins in the kidneys of diabetic rats were found to be back-regulated to normal levels after GSPE therapy. These back-regulated proteins are involved in oxidative stress, glycosylation damage, and amino acids metabolism. Our findings might help to better understanding of the mechanism of DN, and provide novel targets for estimating the effects of GSPE therapy.

The effects of grape seed on apoptosis-related gene expression and oxidative stress in streptozotocin-induced diabetic rats

“…Ulusoy et al have shown that grape seed increased TAS level and decreased TOS level in cyclosporine A-induced nephropathy. 20 In accordance with the findings of our study, Li et al 23 reported antioxidant features of grape seed in STZ-induced diabetic rats. Grape seed proanthocyanidin extract (GSPE) was shown to increase glutathione levels in pancreatic tissue of diabetic rats, resulting in decreased lipid peroxidation, and increased insulin sensitivity by directly affecting the insulin signaling pathways.…”

Grape Seed Procyanidin B2 Inhibits Human Aortic Smooth Muscle Cell Proliferation and Migration Induced by Advanced Glycation End Products

“…GSPB2, as a natural dietary supplement, displays an anti-oxidative property and protects against diabetic complications. 13,[31][32][33] The results of the present study reveal that GSPB2 inhibited the AGE-induced proliferation and migration of HASMCs, and that UCH-L1 may be involved in this process via the inhibition of NF-B activity.…”

“…37,38) A GSPE treatment has decreased the aortic pulse wave velocity and aortic medial thickness by reducing the expression of AGE and RAGE in diabetic aortas. 39) GSPE has also demonstrated protective effects against nephropathy, 32) retinopathy, 31) and damage to peripheral nerves 33) and the cerebral cortex 40) in STZ-induced diabetic rats. We found in this present study that HASMCs stimulated with AGEs had a higher migration cell number and increased proliferation when compared with unstimulated HASMCs in a dosedependent manner.…”

Effects of Grape Seed Proanthocyanidin Extracts on Aortic Pulse Wave Velocity in Streptozocin Induced Diabetic Rats

“…[12][13][14] Moreover, GSPEs have cardiovascular, cerebullar, and renal protective effects. [15][16][17] Our previous experiments showed that GSPEs displayed anti-nonenzymatic glycation and anti-inflammation, reducing receptor of advanced glycation end product (RAGE) protein expression, leading to decreased expression of high level vascular cell adhesion molecule 1 induced by advanced glycation end products (AGEs) in endothelial cells. 18,19) In our present study, we examined the effects of AGEs on the diabetic aorta and evaluated the efficacy of aortic protection by GSPEs.…”