Abstract: SA-PO087
The Effects of PARP Inhibitor Treatment on Early Renal Injury in a Murine Ischemic AKI Model
Session Information
- AKI: Mechanisms - Primary Injury and Repair - II
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Lee, Kyungho, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea (the Republic of)
- Jang, Hye Ryoun, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea (the Republic of)
- Song, Seungmin, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea (the Republic of)
- Baeg, Song in, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea (the Republic of)
- Jeon, Junseok, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea (the Republic of)
- Lee, Jung eun, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea (the Republic of)
- Kim, Yoon-Goo, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea (the Republic of)
- Kim, Dae joong, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea (the Republic of)
- Huh, Wooseong, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea (the Republic of)
Background
Intrarenal robust inflammatory responses following ischemia-reperfusion injury are major factors in the pathogenesis of renal injury in ischemic AKI. Although numerous studies have investigated various agents to modulate immune responses in ischemic AKI, few have demonstrated reproducible effects in animals and humans.
We hypothesized that poly(ADP-Ribose) polymerase(PARP) inhibitor may change the post-ischemic intrarenal immunologic micromilieu favorably by reducing DAMP signal and protect the kidneys from further damage after ischemic injury. The effects of JPI-289 (PARP inhibitor) on early renal injury in a murine ischemia-reperfusion injury model were investigated.
Methods
Bilateral ischemic-reperfusion injury (BIRI) was induced in three groups of 9-week male C57BL/6 mice (control, JPI-289 50mg/kg, and JPI-289 100mg/kg; n=9-10 in each group) by laparotomy approach. Intraperitoneal injection of saline or JPI-289 were performed immediately before reperfusion and at 24 hours after IRI. Serial changes in renal function were assessed up to day 3 following BIRI. The effects of JPI-289 on HK-2 cells after a hypoxic insult were investigated.
Results
Deterioration of renal function was significantly attenuated in the JPI-289 treatment groups in a dose-dependent manner. The expression of proinflammatory cytokines such as IFN-γ, IL-2, and MCP-1 was reduced by the JPI-289 treatment, while intrarenal VEGF expression was higher after IRI in the JPI-289 groups. Intrarenal T cell infiltration following IRI was comparable between control and JPI-289 groups, but intrarenal B cell infiltration was increased by JPI-289 treatment. Low dose (0.5 μg/mL) JPI-289 treatment facilitated proliferation of hypoxic HK-2 cells, but very low dose or high dose treatment did not show favorable effects on hypoxic HK-2 cells.
Conclusion
JPI-289 treatment attenuated early renal injury in a murine ischemic AKI model and facilitated proliferation of hypoxic HK-2 cells. Further studies are needed to identify optimal dosage and administration timing of JPI-289 treatment.