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Vinpocetine reduces cisplatin-induced acute kidney injury through inhibition of NF–κB pathway and activation of Nrf2/ARE pathway in rats

  • Nephrology - Original Paper
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Abstract

Acute kidney injury is a complex clinical disease that is associated with a high incidence of morbidity and mortality. Drug-induced acute kidney injury occurs in approximately 19–33% of hospitalized patients. Cisplatin, one of the most commonly used and effective chemotherapeutic drugs not only exerts anti-tumor effects but also causes renal toxicity damage, affecting its clinical application. Vinpocetine is an anti-inflammatory and antioxidant drug that predominately acts in the nervous system. In this study, we investigated the effects and mechanisms of vinpocetine in an animal model of cisplatin-induced acute renal injury. Rats were randomly divided into three experimental groups. During a 10-day trial, rats in the control group were administered a physiological saline solution; rats in the model group received a 5 mg/kg intraperitoneal injection of cisplatin; and rats in the cisplatin + vinpocetine group received a 5 mg/kg intraperitoneal injection of cisplatin as well as a 5 mg/kg dose of vinpocetine via gavage. We observed that following cisplatin administration, the rats exhibited an increase in blood urea and creatinine levels as well as an increase in their inflammation and oxidative stress levels. In renal tissue, cisplatin caused the morphological changes typical of acute tubular injury. Vinpocetine reduced the cisplatin-induced acute renal function damage and tubular injury. In both in vivo and in vitro experiments, we found that vinpocetine can confer protection of rat renal cells by inhibiting the NF–κB signaling pathway and activating the Nrf2/ARE signaling pathway. Therefore, vinpocetine is a promising therapeutic drug for the treatment of cisplatin-induced acute kidney injury.

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Acknowledgements

We sincerely thank Wuhan Central Hospital, Wuhan, Hubei, China, for the project support. This work was supported by the Wuhan Municipal Health Commission (No. WZ16A01).

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Authors and Affiliations

  1. Department of Breast and Thyroid Surgery, Zhongnan Hospital, Hubei Key Laboratory of Tumor Biological Behaviors, Hubei Cancer Clinical Study Center, Wuhan University, Wuhan, 430071, Hubei, China

    Wenjing Song, Liang Ding, Yan Yang, Xin He, Pengju Gong & Jingwei Zhang

  2. School of Basic Medical Sciences, Department of Pathology and Pathophysiology, Wuhan University, Wuhan, 430071, Hubei, China

    Weinan Yin, Yang Gao, JingJing Xu & Lei Wei

  3. Division of Nephrology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, Hubei, China

    Wenli Chen

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Contributions

LD and YY helped design and implement animal experiments. WY, YG, and JX provided technical support in cell experiments. The first draft of the manuscript was written by WS and all authors commented on the previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Wenli Chen or Jingwei Zhang.

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The animal study was reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) and the ABSL-3 Institutional Biosafety Committee (IBC). All experiments were performed in strict accordance with the recommendations of the National Institutes of Health Laboratory Animal Care and Use Guidelines.

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Song, W., Yin, W., Ding, L. et al. Vinpocetine reduces cisplatin-induced acute kidney injury through inhibition of NF–κB pathway and activation of Nrf2/ARE pathway in rats. Int Urol Nephrol 52, 1389–1401 (2020). https://doi.org/10.1007/s11255-020-02485-z

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