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Leonurine attenuates cisplatin nephrotoxicity by suppressing the NLRP3 inflammasome, mitochondrial dysfunction, and endoplasmic reticulum stress

  • Nephrology - Original Paper
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Abstract

Purpose

Cisplatin has been widely accepted as an effective chemotherapy drug with various side effects, including nephrotoxicity. The mechanisms of cisplatin-induced acute kidney injury (AKI) are complex, and there are limited renoprotective approaches. Leonurine is the main active compound of a Chinese herb and has recently been reported to have a protective effect on the kidneys. This study aimed to verify the renoprotective effect of leonurine in attenuating cisplatin-induced AKI and explore the potential associated mechanisms.

Methods

C57BL/6 mice were divided into four groups (Sham, Cisplatin, Leonurine, and Cisplatin + Leonurine). Mice in the leonurine-treated groups were pretreated with a daily intraperitoneal injection of 25 mg/kg leonurine. AKI was induced by injecting cisplatin once intraperitoneally at 20 mg/kg body weight. Mice were killed on day 5. Kidney injury was assessed using a serum biochemical and histological assay. Apoptosis was evaluated using a terminal deoxyribonucleotide transferase-mediated dUTP nick-end labeling (TUNEL) staining assay and Western blot. Antioxidant enzymes were detected using commercial kits. The improvement in inflammasome activation, mitochondrial dysfunction, and endoplasmic reticulum stress (ERS) were assessed by polymerase chain reaction (PCR) and Western blot, respectively.

Results

Leonurine treatment improved kidney function by preventing renal tubular injury and apoptosis. Expression of nucleotide-binding leucine-rich repeat and pyrin domain containing protein 3 (NLRP3) inflammasome components and inflammatory cytokines, mitochondrial dysfunction, and ERS were all alleviated by leonurine.

Conclusion

The results indicate that leonurine plays a protective role in cisplatin-induced AKI and may represent an effective multi-targeted intervention strategy.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (81970609); “The Belt and Road international cooperation project” (18410741500) and “Interdisciplinary program of Shanghai Jiao Tong University” (YG2017MS07) and “Science and Technology Innovation Fund of Shanghai Ninth People’s Hospital” (CK2019010).

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Authors and Affiliations

  1. Division of Nephrology, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiaotong University, 639 Zhizaoju Road, Shanghai, 200011, China

    Qi Zhang, Yan Tong, Xiao Bi, Lin Chen, Jianxin Lu & Wei Ding

  2. Zibo Center for Disease Control and Prevention, 44 Dongyi Road, Shandong, 255020, China

    Qiuhong Sun

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  1. Qi Zhang
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  2. Qiuhong Sun
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  7. Wei Ding
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Correspondence to Jianxin Lu or Wei Ding.

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All the animal experiments were approved by the Animal Care Committee at Shanghai Jiao Tong University and carried out in accordance with institutional guidelines.

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Zhang, Q., Sun, Q., Tong, Y. et al. Leonurine attenuates cisplatin nephrotoxicity by suppressing the NLRP3 inflammasome, mitochondrial dysfunction, and endoplasmic reticulum stress. Int Urol Nephrol 54, 2275–2284 (2022). https://doi.org/10.1007/s11255-021-03093-1

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