Abstract: TH-PO292

Prothymosin Alpha-Derived Peptide Prevents Cisplatin-Induced AKI

Session Information

Category: Acute Kidney Injury

  • 001 AKI: Basic

Authors

  • Torigoe, Kenta, Nagasaki University Hospital , Nagasaki, Japan
  • Obata, Yoko, Nagasaki University Hospital , Nagasaki, Japan
  • Torigoe, Miki, Nagasaki University Hospital , Nagasaki, Japan
  • Koji, Takehiko, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  • Ueda, Hiroshi, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  • Nishino, Tomoya, Nagasaki University Hospital , Nagasaki, Japan
Background

Cisplatin is one of the most used drugs for cancer treatment. However, cisplatin induces nephrotoxicity via apoptosis, necrosis or vasoconstriction, and this side effect limits clinical application of cisplatin. Prothymosin alpha (ProTα) is reported to exert protective effects against ischemia-induced necrosis and apoptosis in the brain and retina. Recently, the 6-amino acid peptide/P6Q (NEVDQE), modified active core 6-amino acid peptide (a.a.51-56) in ProTa, also showed protective effect against retinal ischemia. Therefore, in this study, we investigated the renoprotective effect of P6Q against cisplatin-induced acute kidney injury (AKI).

Methods

In vitro study, HK-2 cells were treated with cisplatin (12.5μM) for 24hrs to evaluate the cell viability by MTT assay. ProTα protein (0-40nM) or P6Q (0-100μM) was added 30 minutes before cisplatin treatment. In vivo study, 8 week old male Wistar rats were divided into 3 groups: vehicle-treated group, cisplatin (8mg/kg)-treated group, cisplatin-treated group with P6Q (30mg/kg) injection. P6Q was injected 30 minutes before cisplatin treatment. Renal function was assessed by measuring serum creatinine. Renal histological change was assessed by PAS staining, and apoptosis of renal tubular cell was assessed by active caspase 3 and TUNEL staining. Renal hypoxia was assessed by HIF1α staining.

Results

Cisplatin treatment reduced the viability of HK-2 cells in vitro. Administration of ProTα improved cell viability dose-dependently. Furthermore, P6Q administration was more effective to suppress the cytotoxicity by cisplatin compared with ProTa. Thus, we focused to investigate the protective effect of P6Q against cisplatin-induced AKI in vivo. Serum creatinine level peaked at 5 days after cisplatin treatment. Histologic examination revealed extensive tubular damage in cisplatin-treated rats. Cisplatin treatment also increased the active caspase 3 positive area, number of TUNEL-positive apoptotic cells and HIF1α positive area at day 5. P6Q injection significantly suppressed cisplatin-induced AKI and apoptosis of tubular cells, but not HIF1α expression.

Conclusion

We showed the renoprotective effect of ProTα-derived peptide against cisplatin-induced AKI via suppression of apoptosis. Our results suggest that ProTa-derived peptide may become a preventive drug for cisplatin-induced AKI.