Haybar Habib, Shahrabi Saeid, Rezaeeyan Hadi, Jodat Hosein, Saki Najmaldin
Atherosclerosis Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Department of Biochemistry and Hematology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran.
J Cell Physiol. 2019 Sep;234(9):14500-14506. doi: 10.1002/jcp.28292. Epub 2019 Feb 15.
Arsenic trioxide (ATO) is a drug commonly used for the treatment of acute promyelocytic leukemia (APL). Although ATO has been shown to cause significant improvement in patients, it is associated with serious side effects, which sometimes lead to the patient's death. In this review paper, we examine the reports of ATO-induced cardiotoxicity in APL patients and evaluate the strategies to reduce the incidence of such toxicity.
The key search terms were "arsenic trioxide," "acute promyelocytic leukemia," "cardiotoxicity," "molecular pathway," and "biomarker."
Studies have indicated the involvement of several molecular pathways in ATO-induced cardiotoxicity. These pathways increase the production of reactive oxygen species by interfering with intracellular calcium homeostasis as well as impairing the transfer of calcium into endoplasmic reticulum and mitochondria. On the other hand, increasing or decreasing expressions of some microRNAs (miRs) have been shown to play a role in cardiotoxicity.
Finally, it can be stated that given the essential role of molecular pathways in cardiotoxicity and considering the fact these pathways impair the regulation of miRs expression, identification of molecular pathways involved in ATO-induced cardiotoxicity aimed at targeting miRs could be a new therapeutic strategy to prevent cardiotoxicity.
三氧化二砷（ATO）是一种常用于治疗急性早幼粒细胞白血病（APL）的药物。尽管ATO已被证明能使患者病情显著改善，但它会引发严重的副作用，有时甚至导致患者死亡。在这篇综述论文中，我们研究了APL患者中ATO诱导心脏毒性的报告，并评估降低此类毒性发生率的策略。
关键检索词为“三氧化二砷”“急性早幼粒细胞白血病”“心脏毒性”“分子途径”和“生物标志物”。
研究表明，ATO诱导的心脏毒性涉及多种分子途径。这些途径通过干扰细胞内钙稳态以及损害钙向内质网和线粒体的转运来增加活性氧的产生。另一方面，一些微小RNA（miRs）表达的增加或减少已被证明在心脏毒性中起作用。
最后，可以说鉴于分子途径在心脏毒性中的重要作用，并且考虑到这些途径会损害miRs表达的调控，识别参与ATO诱导心脏毒性的分子途径并针对miRs进行靶向治疗可能是预防心脏毒性的一种新治疗策略。
