Protective Effect of A New Peptide HS1002 Against Cisplatin-Induced Acute Kidney Injury

Author(s): Joo Hee Han, Hyun Ji Noh, Ju Ri Kim, Haeun Lee, Jae Hyeon Park, Hyung Sik Kim

Background: The administration of the chemotherapeutic agent cisplatin (CDDP) to patients with cancer is limited by the occurrence of acute kidney injury (AKI), with no effective protective therapies currently available. The present study investigated the protective effects of HS1002 against CDDP-induced nephrotoxicity in Sprague-Dawley rats. Methods: HS1002 was administered subcutaneously at 10 mg/kg for 3 days consecutively, following intraperitoneal injection of CDDP (6 mg/kg). All rats were euthanized 72 h after CDDP administration. Histopathological examination, AKI biomarkers, apoptosis, and oxidative damage were evaluated. Results: HS1002 protected against CDDP-induced cytotoxicity and apoptotic cell death in rats. The CDDP-induced elevation of serum blood urea nitrogen (BUN) and creatinine (sCr) levels were significantly ameliorated by HS1002. Additionally, urinary excretion of kidney injury markers, including kidney injury molecule-1 (KIM-1), selenium-binding protein-1 (SBP-1), and neutrophil gelatinase-associated lipocalin (NGAL), were significantly reduced. Further-more, HS1002 markedly improved antioxidant enzyme activities and reduced DNA damage in CDDP-treated rat kidneys. Notably, HS1002 administration inhibited telomere shortening and restored apoptosis regulation through the extracellu-lar signal-regulated kinase signaling pathway, enhancing protection against renal injury. Histopathological examinations confirmed the HS1002 protective effects against CDDP-induced renal injury. However, HS1002 did not affect the anti-cancer activity of CDDP in the tumor xenograft model. Conclusions: These findings suggest that HS1002 is a potential adjuvant therapy in cancer patients with undergoing CDDP therapy by preventing CDDP-induced nephrotoxicity. Collectively, HS1002 may serve as a therapeutic agent for preventing CDDP-induced AKI in patients with solid tumors.