Protective effects of grape seed proanthocyanidins on podocytes against injury induced by glucolipotoxicity

Abstract

Diabetic nephropathy (DN) is the most common cause of end-stage renal failure, oxidative damage and iron metabolism disorder are related to DN progression, but the exact pathogenesis remains unclear. Grape seed proanthocyanidins extract (GSPE) are one of the most widely distributed polyphenols with antioxidant properties. Here, we evaluate the mechanism by which GSPE alleviates podocyte damage induced by high glucose and palmitic acid (HG/PA). Podocytes were cultured in groups in normal environment; these were based on whether HG/PA and ML385 were present and the concentrations GSPE 10 mg/L, GSPE 25 mg/L, and GSPE 50 mg/. The flow cytometer, immunofluorescence staining, western blot, quantitative real time-PCR (qRT-PCR), kit methodand, and fluorescence microscope were used, respectively. After HG/PA intervention, the podocyte morphology was destroyed, the survival rate was reduced, the cell apoptosis was increased, and the fluorescence intensity of ROS detection was increased, iron metabolism was disordered. After adding ML385, increased oxidative damage to podocyte, nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream protein and mRNA expression levels were significantly reduced. However, the application of different concentrations of GSPE can reverse these situations. Our findings indicate that GSPE regulates intracellular iron metabolism disorders and reduces oxidative damage of podocytes possibly through the activation of the Nrf2 signaling pathway.