Canagliflozin protects against cisplatin-induced acute kidney injury by AMPK-mediated autophagy in renal proximal tubular cells

Cheol Ho Park, Bin Lee, Myeonggil Han, Woo Joong Rhee, Man Sup Kwak, Tae Hyun Yoo, Jeon Soo Shin

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7 Citations (Scopus)


Sodium-glucose cotransporter 2 inhibitors, which are recently introduced as glucose-lowering agents, improve cardiovascular and renal outcomes in patients with diabetes mellitus. These drugs also have beneficial effects in various kidney disease models. However, the effect of SGLT2 inhibitors on cisplatin-induced acute kidney injury (AKI) and their mechanism of action need to be elucidated. In this study, we investigated whether canagliflozin protects against cisplatin-induced AKI, depending on adenosine monophosphate-activated protein kinase (AMPK) activation and following induction of autophagy. In the experiments using the HK-2 cell line, cell viability assay and molecular analysis revealed that canagliflozin protected renal proximal tubular cells from cisplatin, whereas addition of chloroquine or compound C abolished the protective effect of canagliflozin. In the mouse model of cisplatin-induced AKI, canagliflozin protected mice from cisplatin-induced AKI. However, treatment with chloroquine or compound C in addition to administration of cisplatin and canagliflozin eliminated the protective effect of canagliflozin. Collectively, these findings indicate that canagliflozin protects against cisplatin-induced AKI by activating AMPK and autophagy in renal proximal tubular cells.

Original languageEnglish
Article number12
JournalCell Death Discovery
Issue number1
Publication statusPublished - 2022 Dec

Bibliographical note

Funding Information:
The Physician-Scientist program of Yonsei University College of Medicine is gratefully acknowledged. This work was supported by grants from the National Research Foundation of Korea (NRF) funded by the Korean government (MEST) (2017R1A2B3006704, 2019R1A6A1A03032869, 2021R1I1A1A01044809), and the Research Center Program of the Institute for Basic Science (IBS) in Korea (IBS-R026-D1).

Publisher Copyright:
© 2021, The Author(s).

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research


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