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Artesunate Inhibits Renal Ischemia-Reperfusion-Mediated Remote Lung Inflammation Through Attenuating ROS-Induced Activation of NLRP3 Inflammasome

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Abstract

The molecular mechanisms of acute lung injury (ALI) are closely associated with nucleotide-binding domains and leucine-rich repeat (NLR) pyrin domains containing 3 (NLRP3) inflammasome, in which alveolar macrophages (AMs) exert an essential function. Our study has been proved that artesunate (AS) inhibits ALI. Nevertheless, the inhibition actions of AS on activation of NLRP3 in renal ischemia-reperfusion (RIR)-mediated ALI remain to be further discussed. Male Sprague-Dawley rats were randomly assigned into four groups: sham + NS, sham + AS, RIR + NS, and RIR + AS. RIR-mediated ALI was performed through bilateral renal pedicle occlusion for 60 min followed by reperfusion for 24 h. AS (15 mg/kg) or NS was injected intraperitoneal to rat 1 h before RIR treatment. AMs were rendered hypoxic (0.5%) for 2 h and reoxygenated for 24 h. Lung injury index and histology, and inflammatory cells and cytokine release in the BALF and AMs were examined. The protein and mRNA levels of NLRP3, ASC, and caspase-1 in the lung and AMs were evaluated via Western blot and real-time RCR. In this research, we indicated that AS preconditioning inhibited RIR-mediated lung damage, vascular permeability, and edema in rats. AS reduced RIR-mediated ALI, as characterized by abatement in the count of inflammatory cells, and the production of inflammatory cytokines in the BALF. AS administration inhibited the number of F4/80-positive cells, the activity of myeloperoxidase, and the fiery cytokines mRNA expression in lung samples of RIR-stimulated rats. Furthermore, AS alleviated the activity of caspase-1 and activation of NLRP3 through depending on reactive oxygen species (ROS). An in vitro finding that AS mitigated hypoxia/reoxygenation-mediated activation of AMs partially supported in vivo study. In a word, these findings demonstrate that AS pretreatment attenuated RIR-mediated ALI potentially through reducing ROS-induced activation of the NLRP3 inflammasome.

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Authors and Affiliations

  1. Department of Anesthesiology, Cangzhou Central Hospital, Hebei Medical University, No.16 Xinhua West Road, Yunhe District, Cangzhou, Hebei, China

    Zhaohui Liu, Min Qu, Lili Yu, Panpan Song & Yulin Chang

Authors
  1. Zhaohui Liu
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  2. Min Qu
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  3. Lili Yu
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  4. Panpan Song
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  5. Yulin Chang
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Contributions

Zhaohui Liu wrote the main manuscript text and prepared all figures. Min Qu and Zhaohui Liu performed the animal model and collected the samples. Lili Yu, Panpan Song, and Yulin Chang helped to revise the manuscript. Min Qu and Zhaohui Liu conceived the study and revised the manuscript. Min Qu and Zhaohui Liu provided the funding support. All authors reviewed the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Zhaohui Liu.

Ethics declarations

All procedures were performed in accordance with the Declaration of Helsinki of the World Medical Association. The study was approved by the ethics committee of Cangzhou Central Hospital, Cangzhou, Hebei, China.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Liu, Z., Qu, M., Yu, L. et al. Artesunate Inhibits Renal Ischemia-Reperfusion-Mediated Remote Lung Inflammation Through Attenuating ROS-Induced Activation of NLRP3 Inflammasome. Inflammation 41, 1546–1556 (2018). https://doi.org/10.1007/s10753-018-0801-z

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  • DOI: https://doi.org/10.1007/s10753-018-0801-z

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