心脏毒性
三氧化二砷
细胞凋亡
自噬
程序性细胞死亡
药理学
氧化应激
活性氧
急性早幼粒细胞白血病
医学
化学
癌症研究
细胞生物学
毒性
生物化学
生物
内科学
基因
维甲酸
作者
Linya Wang,Shuguang Liu,Chao Gao,Hui Chen,Jing Li,Jiran Lu,Yuan Yuan,Xueling Zheng,Hongbo He,Xixi Zhang,Ruidong Zhang,Yuanyuan Zhang,Ying Wu,Wei Lin,Huyong Zheng
标识
DOI:10.1177/09603271211064537
摘要
Arsenic trioxide (ATO) has been found to be effective in acute promyelocytic leukemia. However, ATO-induced severe cardiotoxicity limits its clinical application. To date, the mechanisms of ATO-induced cardiotoxicity remain unclear. It is hypothesized that ferroptosis may trigger ATO-induced cardiotoxicity; however, this has not yet been investigated. To clarify this hypothesis, rat cardiomyocyte H9c2 cells were treated with ATO with or without ferrostain-1 (Fer-1). The results indicated that ATO exposure induced H9c2 cell death and apoptosis, and the ferroptosis inhibitor Fer-1, administered for 24 h before ATO exposure, suppressed ATO-induced cell death, and apoptosis, as determined by Annexin V-APC/7-AAD apoptosis assay. Furthermore, Fer-1 displayed a cardioprotective effect through inhibiting the ATO-induced production of intracellular reactive oxygen species, improving the ATO-induced loss of the mitochondrial membrane potential, alleviating hyperactive endoplasmic reticulum stress, and alleviating the ATO-induced impairment in autophagy in H9c2 cells. Overall, the cardioprotective effect of Fer-1 against ATO-induced cell injury implies that ATO may trigger ferroptosis to induce cardiotoxicity. These findings lay the foundation for exploring the potential value of ferroptosis inhibitors against ATO-induced cardiotoxicity in the future.
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