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Neferine mitigates cisplatin-induced acute kidney injury in mice by regulating autophagy and apoptosis

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Abstract

Purpose

The nephrotoxicity caused by cisplatin severely limits the application and affects related platinum-based therapeutics. Neferine is a dibenzylisoquinoline alkaloid extracted from a Chinese medicinal herb (Nelumbo nucifera Gaertn), which can decrease cisplatin-induced apoptosis of NRK-52E cells by activating autophagy in vitro in our previous study. In this article, we aimed to further investigate the protective effect of neferine, against to the cispltain-induced kidney damage in mice.

Methods

Six groups were designed in our study. Renal index, mice serum creatinine and blood urea nitrogen levels were detected after the mice were killed. HE staining was used to observe the pathological changes of each group. The apoptosis of mouse kidney tissue was detected by TUNEL. Immunofluorescence and Western blot were used to detect the expression of cleaved-caspase3 and LC3. The transmission electron microscope was used to reveal the changes of apoptosis and autophagy of renal tubular epithelial cells in different groups.

Results

In our findings, the pathological changes of acute kidney injury were easily observed in cisplatin-treated mice while those in the neferine-pretreated groups were significantly alleviated. The apoptosis induced by cisplatin in mice increased evidently compared with the control group, which was decreased in the mice with neferine pretreatment. What’ more, we found that autophagy increased obviously in mice pretreated by neferine contrast to the cisplatin-treated mice.

Conclusion

In our study, neferine can effectively alleviate cisplatin-induced renal injury in mice, as well act as an autophagy-regulator in kidney protection.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable requests.

Abbreviations

AKI:

Acute kidney injury

Nef:

Neferine

Cis:

Cisplatin

Scr:

Serum creatinine

BUN:

Blood urea nitrogen

PTs:

Proximal tubules

ROS:

Reactive oxygen species

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Funding

This artice was supported by Changsha Science and Technology Project (NO: kq1907013) and Project of Hunan Provincial Health Commission (NO: 202103020384) and General Project of Changsha Science and Technology Bureau (NO: kq2001008).

Author information

Author notes

  1. Hui Li, Huipeng Ge, Xiaoyun Song and Xin Tan are co-first author.

Authors and Affiliations

  1. Department of Respiratory Medicine, The First Hospital of Changsha, Changsha, 410008, Hunan, China

    Hui Li

  2. Department of Nephrology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China

    Huipeng Ge, Qi Xiong, Yizi Gong, Linlin Zhang, Yikai He, Weiwei Zhang, Peng Zhu & Xiangcheng Xiao

  3. Department of Science and Education, The First Hospital of Changsha, Changsha, 410008, Hunan, China

    Xiaoyun Song

  4. Department of Pediatrics, The First Hospital of Changsha, Changsha, 410008, Hunan, China

    Xin Tan

  5. Department of Pathology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China

    Wei Lin

  6. National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China

    Huipeng Ge, Wei Lin & Xiangcheng Xiao

Authors
  1. Hui Li
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  2. Huipeng Ge
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  3. Xiaoyun Song
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  4. Xin Tan
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  9. Weiwei Zhang
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  10. Peng Zhu
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  11. Wei Lin
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  12. Xiangcheng Xiao
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Contributions

LH and LW originated the idea and designed the study. LH, GH, SX and TX conducted the major experiments, analyzed the study and wrote the manuscript. XQ, GY, ZL, HY, ZW and ZP conducted partial of the experiments and provided some materials. LW and XX supported the editing and critical revision of the manuscript.

Corresponding authors

Correspondence to Wei Lin or Xiangcheng Xiao.

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Conflict of interest

The authors declare that they have no competing interests.

Human and animal rights

The present study complied with the protocols approved by the ethics committee of Xiangya Hospital, Central South University. This article does not contain any studies with human participants.

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Li, H., Ge, H., Song, X. et al. Neferine mitigates cisplatin-induced acute kidney injury in mice by regulating autophagy and apoptosis. Clin Exp Nephrol 27, 122–131 (2023). https://doi.org/10.1007/s10157-022-02292-z

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  • DOI: https://doi.org/10.1007/s10157-022-02292-z

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