Abstract
Cystic echinococcosis (CE), which primarily affects the liver, is associated with hepatocyte injury, although the underlying cellular and molecular mechanisms remain unclear. The aim of this study was to determine whether hepatocyte injury caused by Echinococcus granulosus sensu lato involves pyroptosis mediated through the ROS-NLRP3 inflammasome pathway. AML-12 hepatocytes were exposed to E. granulosus excretory-secretory products (ESPs), and cell viability, LDH release, cell death, and NLRP3 inflammasome-mediated pyroptosis were evaluated. The results indicated that ESP treatment reduced cell viability, increased LDH release and cell death, and upregulated markers of NLRP3 inflammasome-dependent pyroptosis. Pharmacological inhibition of NLRP3 with MCC950 markedly attenuated ESP-induced cytotoxicity and pyroptosis, confirming the critical role of NLRP3 activation in this process. Additionally, the ROS scavenger N-acetyl-L-cysteine (NAC) suppressed pyroptosis and reduced inflammasome activation, indicating that ESP-induced pyroptosis is ROS dependent. All of these results point to the possibility that ESPs cause hepatocyte damage in CE by inducing hepatocyte pyroptosis via the ROS-NLRP3 inflammasome pathway.
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Acknowledgements
We would like to thank the staff of Shihezi slaughterhouse in Xinjiang Province for donating their abandoned sheep liver.
Funding
This work was supported by the National Natural Science Foundation of China (Grant number 81560334 to H.L.), the Key research and development program of Sichuan Provincial Science and Technology Department (Grant number 2022YFS0231 to H.L.) and the Chengdu Medical College Graduate Student Innovation Fund (Grant number YCX2024-01-08 to J.C.). The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.
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J.C. and J.Q.C. carried out most of the experiments and wrote the manuscript. H.W.L. carried out statistical analysis. Y.J. designed the project and experiments. J.C. prepared figures. J.C. and H.L. were responsible for acquiring funding for this project. All authors contributed to the manuscript and have read and approved the final version of the manuscript.
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Cao, J., Chen, J., Li, H. et al. ROS-NLRP3 participates in the pyroptosis response of excretory-secretory products from protoscoleces of Echinococcus granulosus in hepatocytes. Sci Rep (2026). https://doi.org/10.1038/s41598-026-45127-7
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DOI: https://doi.org/10.1038/s41598-026-45127-7
