MCC950 attenuates doxorubicin-induced myocardial injury in vivo and in vitro by inhibiting NLRP3-mediated pyroptosis

• DOI: 10.1016/j.biopha.2021.112133
• Publication Date: 2021-08-31T02:49:51Z
• Authors: Lei Zhang; Yue-Hua Jiang; Cundong Fan; Qian Zhang; Yong-Hao Jiang; Yan Li; Yi-Tao Xue
• Keywords: Pyroptosis

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 in mice H9c2 cells was investigated, effects were fully explored. The results showed that co-treatment significantly improved function, inhibited inflammatory fibrosis, attenuated cardiomyocyte pyroptosis DOX-treated mice. Mechanismly, had to inhibit cleavage NLRP3, ASC, Caspase-1, IL-18, IL-1β GSDMD vivo. Moreover, vivo suppressed cytotoxicity as through same molecular mechanism. Taken together, our findings validated attenuate doxorubicin-induced vitro by inhibiting NLRP3-mediated pyroptosis.