Aleksandr S. Netrebenko , Tatiana G. Pokrovskaya, Elena G. Netrebenko, Margarita V. Edamenko, Dmitriy B. Kuzmin, Aleksandr V. Paulauskas, Dmitry S. Skuryatin, Ekaterina I. Skuryatina, Igor A. Efremenko, Tatyana V. Avtina

Modeling of cisplatin-induced acute kidney injury and its correction using polydatin

Introduction

Modeling of cisplatin-induced acute kidney injury and its correction using polydatin. Develops an optimal rat model for cisplatin-induced acute kidney injury (AKI) and proves the nephroprotective potential of polydatin. Cisplatin 5 mg/kg on days 1 & 8 is optimal.

Abstract

Introduction: Cisplatin is a key drug used for anticancer therapy. However, its use is often accompanied by the development of acute kidney injury. The aim of this study was to develop an optimal model of cisplatin-induced kidney injury in rats and use it to study the nephroprotective properties of polydatin. Materials and Methods. The experiment was performed in 100 male Wistar rats. To test the cisplatin-induced acute kidney injury model, seven groups (n=10) were formed. Animals were administered cisplatin intraperitoneally at doses of 1 mg/kg, 5 mg/kg, 10 mg/kg, and 20 mg/kg once or twice on days 1 and 8. Nephrotoxicity was corrected using polydatinat doses of 4 mg/kg and 12 mg/kg. Alpha-tocopherol acetate at a dose of 75 mg/kg was used as a reference drug. The test drug and the reference drug were administered intragastrically daily for 14 days. Nephroprotection was assessed based on the following parameters: creatinine, urea, potassium and sodium ions in the blood serum, glomerular filtration rate, fractional sodium extraction, and renal parenchyma microcirculation. Results and Discussion. The optimal model of cisplatin-induced acute kidney injury was the one in which cisplatin was administered at a dose of 5 mg/kg on days 1 and 8 of the experiment. This was evidenced by an increase in creatinine level to 124.0 ± 8.6 μmol/L and urea to 20.3 ± 1.2 mmol/L, a decrease in glomerular filtration rate to 0.08 ± 0.01 mL/minand a 2-fold deterioration in microcirculation. Other models were significantly inferior in representativeness. Polydatindemonstrated dose-dependent nephroprotective properties, which was confirmed by improvement in laboratory and instrumental parameters. Conclusions. The use of cisplatin at a dose of 5 mg/kg intraperitoneally on days 1 and 8 results in optimal modeling of cisplatin-induced acute kidney injury in rats in the experiment. The potential of intragastric use of polydatin for nephroprotection in cisplatin-induced acute kidney injury has been proven in dosages of 4 mg/kg and 12 mg/kg per day for 14 days.

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