坏死性下垂
地塞米松
阿霉素
心脏毒性
程序性细胞死亡
药理学
细胞凋亡
医学
癌症研究
蒽环类
化学
内科学
化疗
癌症
生物化学
乳腺癌
作者
Xiaoxue Yu,Yuanyuan Ruan,Xiuqing Huang,Lin Dou,Ming Lan,Ju Chen,Beidong Chen,Huan Gong,Que Wang,Mingjing Yan,Shenghui Sun,Quan Qiu,Xiyue Zhang,Yong Man,Weiqing Tang,Jian Li,Tao Shen
标识
DOI:10.1016/j.bbrc.2019.12.027
摘要
Doxorubicin, as a first line chemotherapeutic agent, its usage is limited owing to cardiotoxicity. Necroptosis is a new form of programmed cell death, and recent investigations indicated that necroptosis is vitally involved in serious cardiac pathological conditions. Dexrazoxane is the only cardiac protective drug approved by FDA for anthracycline. We aimed to explore whether and how dexrazoxane regulates doxorubicin-induced cardiomyocyte necroptosis. First, doxorubicin could cause heart failure and reduce cardiomyocyte viability by promoting cell apoptosis and necroptosis in vivo and in vitro. Second, necroptosis plays an important role in doxorubicin induced cardiomyocyte injury, which could be inhibited by Nec-1. Third, dexrazoxane increased cell viability and protect heart function by decreasing both cardiomyocyte apoptosis and necroptosis after doxorubicin treatment. Forth, dexrazoxane attenuated doxorubicin-induced inflammation and necroptosis by the inhibition of p38MAPK/NF-κB pathways. These results indicated that dexrazoxane ameliorates cardiotoxicity and protects heart function by attenuating both apoptosis and necroptosis in doxorubicin induced cardiomyocyte injury.
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