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.
Highlights
Post-contrast acute kidney injury (PC–AKI), described as a decrease in renal function that follows the intravascular administration of contrast medium, is one of the leading causes of hospitalacquired acute kidney injury (Takahashi et al, 2017; Van Der Molen et al, 2018)
Serum Cr, blood urea nitrogen (BUN) and cystatin C (CysC) levels were significantly lower in the Res+post-contrast acute kidney injury (PC–AKI) group compared to the PC–AKI group (P = 0.038; P = 0.035; P = 0.048, respectively), whereas there was no significant difference between Cont and Res groups (P = 0.562; P = 0.631; P = 0.895, respectively)
We found that the Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) protein level was higher (P = 0.447) and the hypoxia-inducible transcription factor-1α (HIF-1α) protein level lower (P = 0.112) in the Res+PC–AKI group compared to the PC–AKI group, but no statistical differences were observed between these
Summary
Post-contrast acute kidney injury (PC–AKI), described as a decrease in renal function that follows the intravascular administration of contrast medium, is one of the leading causes of hospitalacquired acute kidney injury (Takahashi et al, 2017; Van Der Molen et al, 2018). This type of injury is associated with adverse short- and long-term outcomes (Maioli et al, 2012; Chalikias et al, 2016). Accumulated experimental evidence suggests that resveratrol may inhibit the inflammatory response and tubular apoptosis, and scavenge oxygen free radicals in cisplatin-induced nephropathy, renal ischemic/reperfusion injury and diabetic nephropathy (Kim et al, 2011; Gu et al, 2016; Xiao et al, 2016)
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