期刊
BIOMEDICINE & PHARMACOTHERAPY
卷 143, 期 -, 页码 -出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2021.112133
关键词
MCC950; Doxorubicin; Myocardial injury; NLRP3 inflammasome; Inflammatory; Pyroptosis
资金
- Project Found by National Natural Science Foundation of China [81774247, 81804045]
- Shandong Province Famous and Old Traditional Chinese Medicine Expert Inheritance Studio Construction Project [201992]
- Natural Science Foundation of Shandong Province [ZR2020MH134]
In this study, MCC950 was found to significantly improve myocardial function, inhibit inflammation and myocardial fibrosis, and attenuate cardiomyocyte pyroptosis in mice treated with DOX. Mechanistically, MCC950 inhibited the cleavage of NLRP3, ASC, Caspase-1, IL-18, IL-1 beta, and GSDMD induced by DOX in vivo. Overall, MCC950 has the potential to attenuate DOX-induced myocardial injury by inhibiting NLRP3-mediated pyroptosis in vivo and in vitro.
MCC950, an NLRP3 inflammasome inhibitor, displays multiple pharmacological properties. However, the protective potential and underlying mechanism of MCC950 against doxorubicin (DOX)-induced myocardial injury has not been well investigated yet. Herein, DOX-induced myocardial injury in mice and in H9c2 myocardial cells was investigated, and the protective effects and underlying mechanism of MCC950 were fully explored. The results showed that MCC950 co-treatment significantly improved myocardial function, inhibited inflammatory and myocardial fibrosis, and attenuated cardiomyocyte pyroptosis in DOX-treated mice. Mechanismly, MCC950 had the potential to inhibit DOX-induced the cleavage of NLRP3, ASC, Caspase-1, IL-18, IL-1 beta and GSDMD in vivo. Moreover, MCC950 co-treatment in vivo suppressed DOX-induced cytotoxicity as well as inflammatory and cardiomyocyte pyroptosis through the same molecular mechanism. Taken together, our findings validated that MCC950, an NLRP3 inflammasome inhibitor, has the potential to attenuate doxorubicin-induced myocardial injury in vivo and in vitro by inhibiting NLRP3-mediated pyroptosis.
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