Rapamycin Is Not Protective against Ischemic and Cisplatin-Induced Kidney Injury


Autophagy plays an important role in the pathogenesis of acute kidney injury (AKI). Although autophagy activation was shown to be associated with an increased lifespan and beneficial effects in various pathologies, the impact of autophagy activators, particularly, rapamycin and its analogues on AKI remains obscure. In our study, we explored the effects of rapamycin treatment in in vivo and in vitro models of ischemic and cisplatin-induced AKI. The impact of rapamycin on the kidney function after renal ischemia/reperfusion (I/R) or exposure to the nephrotoxic agent cisplatin was assessed by quantifying blood urea nitrogen and serum creatinine and evaluating the content of neutrophil gelatinase-associated lipocalin, a novel biomarker of AKI. In vitro experiments were performed on the primary culture of renal tubular cells (RTCs) that were subjected to oxygen-glucose deprivation (OGD) or incubated with cisplatin under various rapamycin treatment protocols. Cell viability and proliferation were estimated by the MTT assay and real-time cell analysis using an RTCA iCELLigence system. Although rapamycin inhibited mTOR (mammalian target of rapamycin) signaling, it failed to enhance the autophagy and to ameliorate the severity of AKI caused by ischemia or cisplatin-induced nephrotoxicity. Experiments with RTCs demonstrated that rapamycin exhibited the anti-proliferative effect in primary RTCs cultures but did not protect renal cells exposed to OGD or cisplatin. Our study revealed for the first time that the mTOR inhibitor rapamycin did not prevent AKI caused by renal I/R or cisplatin-induced nephrotoxicity and, therefore, cannot be considered as an ideal mimetic of the autophagy-associated nephroprotective mechanisms (e.g., those induced by caloric restriction), as it had been suggested earlier. The protective action of such approaches like caloric restriction might not be limited to mTOR inhibition and can proceed through more complex mechanisms involving alternative autophagy-related targets. Thus, the use of rapamycin and its analogues for the treatment of various AKI forms requires further studies in order to understand potential protective or adverse effects of these compounds in different contexts.

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acute kidney injury


blood urea nitrogen


dimethyl sulfoxide


Dulbecco’s phosphatebuffered saline


epidermal growth factor


fetal bovine serum; i.p., intraperitoneal (injection)




microtubule-associated protein 1A/1B, light chain 3


mammalian target of rapamycin


mammalian target of rapamycin complex 1




neutrophil gelatinase-associated lipocalin


oxygen-glucose deprivation


renal tubular cells


serum creatinine


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Correspondence to E. Y. Plotnikov.

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Conflict of interest. The authors declare no conflict of interest.

Compliance with ethical norms. The rats were treated according to the protocols evaluated and approved by the Animal Ethics Committee of Belozersky Institute of Physico-Chemical Biology. All procedures were in accordance with the guidelines of the Federation of Laboratory Animal Science Associations (FELASA).

Published in Russian in Biokhimiya, 2019, Vol. 84, No. 12, pp. 1854–1866.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM19–194, September 23, 2019.

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Andrianova, N.V., Zorova, L.D., Babenko, V.A. et al. Rapamycin Is Not Protective against Ischemic and Cisplatin-Induced Kidney Injury. Biochemistry Moscow 84, 1502–1512 (2019) doi:10.1134/S0006297919120095

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  • rapamycin
  • acute kidney injury
  • ischemia
  • cisplatin
  • renal tubular cells
  • autophagy
  • nephroprotection