Resveratrol Protects Against Post-Contrast Acute Kidney Injury in Rabbits With Diabetic Nephropathy

Abstract

Resveratrol (Res) is a multi-functional polyphenol compound that has protective functions in acute kidney diseases. Here, we examined whether the resveratrol could ameliorate post-contrast acute kidney injury (PC-AKI) following diabetic nephropathy (DN), and explored any underlying mechanism(s) in vivo and in vitro. Twenty-four rabbits with DN were randomly divided into four groups: control (Cont), resveratrol (Res), iohexol (PC-AKI), and resveratrol plus iohexol (Res+PC-AKI) groups. Functional magnetic resonance imaging, renal histology, blood and urinary biomarkers, silent information regulator l (SIRT1), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), hypoxia-inducible transcription factor-1α (HIF-1α), and apoptosis-associated protein expression were assessed ex vivo. For in vitro experiments, renal tubular epithelial (HK-2) cells subjected to high glucose conditions were treated with resveratrol, Ex527, an SIRT1 inhibitor, or 2-methoxyestradiol (2-MeOE2), HIF-1α inhibitor, before treatment with iohexol. With regard to the rabbit model of acute renal injury in DN, compared to the PC-AKI group, the Res+PC-AKI group showed decreased levels of cystatin C and urinary neutrophil gelatinase-associated lipocalin, increased pure molecular diffusion (D) and the fraction of water flowing in capillaries (f), a decreased apparent relaxation rate (R2*), renal injury score and apoptosis rate, increased protein expression levels of SIRT1 and PGC-1α, and decreased levels of HIF-1α and apoptosis-associated protein. In addition, iohexol decreased HK-2 cell survival and increased the cell apoptosis rate; results were reversed after treating cells with resveratrol. Resveratrol reduced renal hypoxia, mitochondrial dysfunction and renal tubular cell apoptosis by activating SIRT1-PGC-1α-HIF-1α signaling pathways in PC-AKI with DN.