*Purpose: Robust intrarenal inflammatory responses following ischemia-reperfusion injury (IRI) induce renal injury in ischemic acute kidney injury (AKI). We hypothesized that poly (ADP-Ribose) polymerase (PARP) inhibitor may attenuate the inflammatory cascade in postischemic kidneys by reducing DAMP signals and improve renal outcome after IRI. The effects of a novel PARP inhibitor (JPI-289) on the development renal injury in a murine ischemic AKI model and HK-2 cell hypoxia model were investigated.

*Methods: Bilateral ischemic-reperfusion injury (BIRI) surgery was performed in three groups of 9-week old male C57BL/6 mice (control, JPI-289 50mg/kg, and JPI-289 100mg/kg; n=9-10 in each group). Saline or JPI-289 were injected intraperitoneally immediately before reperfusion during surgery and at 24 hours after IRI. Histologic changes and intrarenal immunologic components were analyzed on day 3 after BIRI. The effect of JPI-289 on HK-2 cells after a hypoxic insult was also investigated.

*Results: Renal functional and structural deterioration was significantly attenuated with JPI-289 treatment. The expression of proinflammatory cytokines such as IFN-γ, IL-2, and MCP-1 following IRI was suppressed by the JPI-289 treatment, whereas intrarenal VEGF expression was increased by JPI-289 treatment in the postischemic kidneys. The infiltration of macrophages and NK cells following IRI was attenuated in groups treated with JPI-289, while intrarenal T cell and B cell infiltration was comparable between control and groups treated with JPI-289. The proliferation of HK-2 cells after hypoxia was facilitated by JPI-289 treatment (0.5 μg/mL).

*Conclusions: JPI-289 treatment mitigated renal injury by changing intrarenal immunologic micromilieu favorably in a murine ischemic AKI model and restored proliferation of HK-2 cells after hypoxia.

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