Niraparib, an FDA-Approved Poly-(ADP-Ribose) Polymerase (PARP) Inhibitor Is Renoprotective against Cisplatin Nephrotoxicity in Ovarian Tumor-Bearing Mice

Background: Cisplatin is one of the most commonly used drugs for the treatment of many solid cancers. However, its dose-limiting side effect is nephrotoxicity, leading to acute kidney injury and chronic kidney disease. We previously demonstrated that genetic or pharmacological suppression of poly(ADP-ribose) polymerase 1 (PARP1) protects against cisplatin nephrotoxicity. PARP1 inhibitors such as olaparib, niraparib, and rucaparib are currently FDA-approved for the treatment of ovarian cancer. In this study, we investigated the effect of niraparib on cisplatin nephrotoxicity in an ovarian tumor-bearing model. Methods: OVCAR3, ovarian cancer cell line cells, bearing mice were established in athymic nude mice and the animals were treated with saline (vehicle), 8 mg/kg cisplatin (once a week), or cisplatin plus 10 mg/kg niraparib (daily). Results: We found that PARP1 inhibition attenuated kidney cell death and tissue damage, preserving renal function during cisplatin treatment in ovarian tumor bearing mice. Furthermore, inhibition of PARP1 attenuated cisplatin-induced inflammation and renal interstitial fibrogenesis. Conclusion: Taken together, these results demonstrate that the FDA-approved PARP inhibitor, niraparib can protect efficaciously against renal tubular cell death during cisplatin nephrotoxicity in tumor bearing mice and could be developed as potential therapeutic agents to improve cisplatin nephrotoxicity.