Mice were assigned randomly into five groups: control group (Cont, n=6), vehicle group (Veh, n=6), ABL group (ABL, n=6), IOP group (n=6), and ABL + IOP group (n=6). Mice in the Cont or ABL group were given saline or ABL (25 mg/kg) via gavage administration for 6 days, respectively. Mice in the IOP + ABL group were first gavage administered with ABL for 6 days. On the sixth day, mice in IOP and IOP + ABL groups were injected intraperitoneally with indomethacin, NG-nitro-l-arginine methyl ester, and IOP. Mice in the Veh group were administered with the same amount of vehicle (methanol). (A,B) Serum creatinine and urea levels were determined by ELISA. (C) Kidney tissues were extracted for HE stain. Scale bar = 100 μm. (D,E) show the kidney weight/body weight (%) and tubular injury score. (F,G) Serum IL-18 and IL-1β levels were determined by ELISA. (H) exhibits the LDH release activity. (I) Proteins were extracted for Western blot. (J–N) The relative protein levels of NLRP3, ASC, cleaved caspase-1, mature GSDMD, and IL-1β were normalized to GAPDH. (O) Schema depicting the mechanisms for renoprotection by ABL against IOP-induced AKI. In vivo and in vitro, the application of IOP significantly up-regulated the expression of NLRP3, caspase-1, ASC, and mature GSDMD, in turn promoting the release of pro-inflammatory cytokines IL-1β and IL-18 to induce pyroptosis and AKI. However, the pretreatment of ABL partly reversed the pyroptosis gene alterations in IOP-injured kidney and ameliorated AKI.