Astaxanthin attenuates contrast-induced acute kidney injury through silent mating-type information regulation 2 homolog-1/peroxisome proliferator-activated receptor γ co-activator–α/NRF1 signaling pathway

Abstract

Objectives: In this study, we established a model of contrast-induced acute kidney injury with iohexol. This model was used to investigate whether astaxanthin (AST) attenuates oxidative stress and apoptosis by activating silent mating-type information regulation 2 homolog-1 (SIRT1) signaling pathway in rat renal tubular epithelial cells (NRK-52E). Materials and Methods: NRK-52E cells were randomly divided into six groups: control group (CON group), vehicle (dimethyl sulfoxide group, iohexol group (I group), AST pretreatment group (AST + I group), AST plus nicotinamide (NA) co-pretreatment group (AST + NA + I group), and NA treatment group (NA + I group). The cellular activity was measured by cell counting kit-8. We estimated the levels of malonaldehyde (MDA) by the thiobarbituric acid method, and the level of intracellular reactive oxygen species (ROS) was measured by flow cytometry. Western blot analysis was conducted to detect the protein levels of SIRT1, peroxisome proliferator-activated receptor γ co-activator–α (PGC-1α), and NRF1. Results: Compared with the CON group, the I group showed suppressed cellular activity; increased levels of MDA and ROS; and decreased levels of SIRT1, PGC-1α, and NRF1 protein. Compared with the I group, AST + I pretreated group showed high cellular activity; low levels of MDA and ROS; and increased levels of SIRT1, PGC-1α, and NRF1 protein. SIRT1 inhibitor NA reversed the protective effect of AST. Compared with the AST + NA + I group, NA + I group showed low cellular activity; high levels of MDA and ROS; and low levels of SIRT1, PGC-1α, and NRF1 protein, which further confirmed the protective effect of AST. Conclusion: AST alleviated iohexol-induced NRK-52E cell injury by decreasing the formation of MDA and ROS and upregulating the SIRT1/PGC-1α/NRF1 signaling pathway.