期刊
BIOMEDICINE & PHARMACOTHERAPY
卷 163, 期 -, 页码 -出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2023.114808
关键词
ACT001; Radiation-induced lung injury; Pyroptosis; Bioinformatics; Inflammasome
ACT001, a prodrug of micheliolide, has potential clinical application in treating thoracic tumors and protecting against radiation-induced lung injury (RILI). This study demonstrates that ACT001 can alleviate RILI, reduce inflammation and fibrosis in lung tissue, and inhibit the activation of the NLRP3 inflammasome and pyroptosis. These findings suggest that ACT001 may serve as a novel protective agent for RILI.
Radiotherapy is a prevalent treatment modality for thoracic tumors; however, it can lead to radiation-induced lung injury (RILI), which currently lacks effective interventions. ACT001, a prodrug of micheliolide, has demonstrated promising clinical application potential, yet its impact on RILI requires further validation. This study aims to investigate the radioprotective effects of ACT001 on RILI and elucidate its underlying mechanism. Sprague-Dawley rats were utilized to induce RILI following 20 Gy X-ray chest irradiation, and lung tissue inflammation and fibrosis were assessed using hematoxylin and eosin (H&E) and Masson staining. Lung injury, inflammation, and oxidative stress markers were evaluated employing commercial kits. Pyroptosis-related differentially expressed genes (DEGs) were analyzed using a microarray dataset from the Gene Expression Omnibus (GEO) database, and their functions and hub genes were identified through protein-protein interaction networks. Pyroptosis-related genes were detected via RT-qPCR, western blotting, immunofluorescence, and immunohistochemistry. The results demonstrated that ACT001 ameliorated RILI, diminished pro-inflammatory cytokine release and fibrosis, and mitigated the activation of the NLRP3 inflammasome while inhibiting pyroptosis in lung tissue. In conclusion, our study reveals that ACT001 can suppress NLRP3 inflammasomemediated pyroptosis and improve RILI, suggesting its potential as a novel protective agent for RILI.
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