Abstract

Contrast-induced acute kidney injury (CI-AKI) poses a significant clinical challenge and contributes to a considerable healthcare burden. Ferroptosis has been increasingly recognized as an important mechanism of renal tubular epithelial cell injury in CI-AKI. Salvianolic acid B (SalB), a natural compound with anti-inflammatory and antioxidant properties, has shown protective effects in various kidney diseases. However, its role in CI-AKI-associated ferroptosis has not been fully clarified. In this study, we established a rat model of CI-AKI by subcutaneous injection of carbon tetrachloride for 6 weeks followed by iopamidol administration, and an in vitro model using iopamidol-treated HK-2 cells. Effects of tubular injury and ferroptosis were examined both in vivo and in vitro. Cycloheximide chase assay, cellular thermal shift assay, and molecular docking were used to assess the binding capacity of SalB to SIRT1. Our results showed that SalB significantly alleviated renal injury, reduced iron accumulation, oxidative stress levels, and lipid peroxidation, upregulated the expression of SLC7A11 and GPX4, and downregulated ACSL4 expression in both iopamidol-treated rat kidneys and HK-2 cells. Mechanistically, SalB targeted and bound to SIRT1, enhancing its stability, thereby promoting Nrf2 upregulation and nuclear translocation, which in turn enhanced the expression of SLC7A11 and GPX4 and attenuated ferroptosis. Silencing either SIRT1 or Nrf2 in HK-2 cells partially abrogated the protective effect of SalB. Collectively, our results support SalB as a viable treatment strategy for CI-AKI.