1. The protective effect of isoflurane pretreatment on liver IRI by suppressing noncanonical pyroptosis of liver macrophages
- Author
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Zuojin Liu, Yucheng Chen, Di-Guang Wen, Xiaoying Wang, Zhihao Feng, and Jiao Lu
- Subjects
Lipopolysaccharides ,Male ,Lipopolysaccharide ,Inflammasomes ,medicine.medical_treatment ,Immunology ,Ischemia ,Inflammation ,Pharmacology ,Systemic inflammation ,Protective Agents ,chemistry.chemical_compound ,Mice ,NLR Family, Pyrin Domain-Containing 3 Protein ,medicine ,Pyroptosis ,Immunology and Allergy ,Animals ,Ischemic Preconditioning ,Isoflurane ,Macrophages ,medicine.disease ,Mice, Inbred C57BL ,Cytokine ,chemistry ,Liver ,Reperfusion Injury ,Anesthetics, Inhalation ,Cytokines ,Calcium ,medicine.symptom ,Intracellular ,medicine.drug - Abstract
Background Liver ischaemia–reperfusion injury (IRI) is a major complication in the perioperative period and often leads to liver failure and even systemic inflammation. Sufficient evidence has demonstrated that isoflurane has anti-inflammatory effects. We aimed to determine whether isoflurane pretreatment protects against liver IRI and to investigate the mechanisms involved in this protection. Methods Male C57BL/6 mice were pretreated with or without isoflurane and subjected to 90 min of 70% liver ischaemia, followed by reperfusion for 6 h. Liver tissues and serum were analysed to assess liver IRI. To probe the mechanisms, liver macrophages isolated from C57BL/6 mice were pretreated with or without emulsified isoflurane for 30 min before incubation with 1 µg/ml lipopolysaccharide (LPS) for 24 h. Inflammatory cytokine production, intracellular Ca2+ levels, caspase-11 expression, NF-κB transcription, and NLRP3 inflammasome activation were assessed by ELISA, an intracellular Ca2+ concentration assay, immunohistochemistry, or Western blotting. Results Isoflurane preconditioning significantly relieved liver IRI in mice and LPS-induced inflammation in liver macrophages. Additionally, isoflurane pretreatment inhibited caspase-11 expression and noncanonical pyroptosis-related production of cytokines (IL-1β and IL-18). Interestingly, isoflurane preconditioning reduced intracellular Ca2+ levels, NF-κB translocation, and NLRP3 inflammasome activation in LPS-induced macrophages. Our results indicated that isoflurane preconditioning ameliorated liver IRI by suppressing noncanonical pyroptosis in liver macrophages. These findings suggest that isoflurane could be a pharmacological agent for liver IRI prevention and thus deserves more attention and further investigation.
- Published
- 2021