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

Authors

DOI:

https://doi.org/10.18413/rrpharmacology.12.1072

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.

 

Graphical Abstract

Keywords:

cisplatin, acute kidney injury, nephrotoxicity, microcirculation, polydatin

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Author Contribution

Aleksandr S. Netrebenko , Belgorod Regional Oncology Clinic

Urologist, Belgorod Regional Oncology Clinic, Belgorod, Russia; e-mail: AlexNetrebenko@mail.ru; ORCID ID: https://orcid.org/0000-0003-2212-0508. Development of the concept of search and analytical work, critical analysis of literature sources, writing review sections, and modeling cisplatin-induced acute kidney injury.

Tatiana G. Pokrovskaya, Belgorod State National Research University

Doctor Habil. of Medical Sciences, Professor, Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: pokrovskaia-tg@mail.ru; ORCID ID: https://orcid.org/0000-0001-6802-5368. Critical review of the manuscript, adding valuable intellectual content, and approval of the final version.

Elena G. Netrebenko, Belgorod Regional Oncology Clinic

Oncologist, Belgorod Regional Oncology Clinic, Belgorod, Russia; e-mail: saprykina5555@yandex.ru; ORCID ID: https://orcid.org/0009-0003-3612-4398. Search for and analysis of literature on chemotherapy nephrotoxicity.

Margarita V. Edamenko, Belgorod Regional Oncology Clinic

Oncologist, Belgorod Regional Oncology Clinic, Belgorod, Russia; e-mail: edamenko@oncology31.ru; ORCID ID: https://orcid.org/0009-0005-1517-2133. Analysis of literature on the mechanisms of cisplatin’s nephrotoxic action and writing sections of the review.

Dmitriy B. Kuzmin, Belgorod Regional State City Hospital №2

Urologist, Belgorod Regional State City Hospital №2, Belgorod, Russia; e-mail: kuzmin.79@bk.ru,ORCID ID: https://orcid.org/0000-0002-0257-6340. Analysis of literature sources on biological markers of nephrotoxicity.

Aleksandr V. Paulauskas

Cardiologist, Belgorod Regional State City Hospital №2, Belgorod, Russia; e-mail: earl_bel@mail.ru. Manuscript preparation for publication.

Dmitry S. Skuryatin, Belgorod State National Research University

Junior researcher, Belgorod State National Research University, Belgorod, Russia; e-mail: 127677@bsuedu.ru; ORCID ID: https://orcid.org/0009-0001-1599-4795. Developing the concept, methodology and investigation.

Ekaterina I. Skuryatina, Belgorod State National Research University

Junior researcher, Belgorod State National Research University, Belgorod, Russia; e-mail: 1386707@bsuedu.ru; ORCID ID: https://orcid.org/0009-0001-5193-4618. Developing the concept, methodology and investigation.

Igor A. Efremenko, Belgorod State National Research University

Chemist-expert, Laboratory for Toxicological Research, Belgorod State National Research University, Belgorod, Russia; e-mail: efremenko_i@bsuedu.ru; ORCID ID: https://orcid.org/0009-0005-5056-2866. Development of the dosage form, technical assistance in animal study, and analysis of the results.

Tatyana V. Avtina

PhD in Pharmaceutical Sciences, Associate Professor, Department of Pharmacology and Clinical Pharmacology, Belgorod State National Research University, Belgorod, Russia; e-mail: tatyanavtina@yandex.ru; ORCID ID: https://orcid.org/0000-0003-0509-5996. Conception of the study, performing the experiments, development of the dosage form, and analysis of the results.

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Published

31-05-2026

How to Cite

Netrebenko AS, Pokrovskaya TG, Netrebenko EG, Edamenko MV, Kuzmin DB, Paulauskas AV, Skuryatin DS, Skuryatina EI, Efremenko IA, Avtina TV (2026) Modeling of cisplatin-induced acute kidney injury and its correction using polydatin. Research Results in Pharmacology 12(2): 35–45. https://doi.org/10.18413/rrpharmacology.12.1072

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Section

Experimental Pharmacology

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