APELA/ELA32 Reduces Iodixanol-induced Apoptosis, Inflammatory Response and Mitochondrial and DNA Damage in Renal Tubular Epithelial Cells

BACKGROUND/AIM: Contrast-induced AKI (CI-AKI) is an important clinical complication of intravascular use of iodinated contrast agents. The aim of the present study was to investigate the renoprotective effect of Apela on contrast-induced acute kidney injury. MATERIALS AND METHODS: Blood samples from patients exposed to iodinated contrast agent were collected to assay for Apela and creatinine levels. The effects of ELA32 (Apela 32) on iodixanol-induced apoptosis, inflammation response, mitochondrial ROS production and DNA damage were examined in NRK-52E renal tubular epithelial cells. RESULTS: Plasma Apela levels were decreased in patients exposed to the contrast agent. Iodixanol-induced apoptosis was reduced in ELA32 treated NRK-52E cells (p<0.05). ELA32 treatment inhibited iodixanol-induced mitochondrial ROS generation (p<0.01). Iodixanol-induced inflammatory cytokines TNFa and IL-6 and inflammatory genes Nrf2 and ICAM-1 were reduced by ELA32 treatment (p<0.01). Reduced Apela expression in iodixanol-treated cells was partially restored by ELA32 treatment (p<0.05). ELA32 treatment suppressed iodixanol-induced up-regulation of DNA damage-associated gene P-ATR and p-CHK1 as well as apoptosis-associated gene C-caspase 3 (p<0.05). CONCLUSION: Administration of iodinated contrast agent reduces Apela expression. ELA32 treatment reduces iodixanol-induced apoptosis, inflammatory response and mitochondrial and DNA damage in renal tubular epithelial cells.