Mechanistically, the current study demonstrated, for the first time, that APO, UMB, and their combination prevented the activation of the NLRP3 inflammasome signaling pathway in ACR-induced AKI by targeting NLRP3, ASC, GSDMD, IL-1β, and caspase-1, which is being investigated as a potential therapeutic approach for various inflammatory conditions, including AKI. This evidence concerns the gene CASP1 and acute kidney injury.