Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C.
Division of Cardiac and Vascular Surgery, Cardiovascular Center, Taichung Veterans General Hospital, Taichung, Taiwan, R.O.C.
In Vivo. 2021 Nov-Dec;35(6):3157-3163. doi: 10.21873/invivo.12610.
BACKGROUND/AIM: The clinical use of arsenic trioxide (AsO) is hampered due to its cardiotoxicity. Therefore, it is critical to prevent AsO-induced loss of endothelial integrity. The purpose of this study was to examine AsO-induced endothelial dysfunction and evaluate the efficacy of crocetin on reversing AsO-induced cardiotoxicity.
Cultured human umbilical vein endothelial cells (HUVECs) were used to examine AsO-induced oxidative stress, apoptosis, production of reactive oxygen species (ROS) and DNA adducts. In addition, the impact of crocetin on AsO-induced cardiotoxicity was evaluated.
AsO decreased the viability of HUVEC cells and led to apoptosis. Additionally, AsO elevated NADPH oxidase activity, and the levels of intracellular ROS. Furthermore, the formamidopyrimidine DNA-glycosylase- and endonuclease III-digestible adducts were induced by AsO Crocetin treatment reversed the AsO-induced reduction in cell viability, the induction of apoptosis, the activation of NADPH oxidase activity, ROS levels and DNA adducts.
Crocetin protects from AsO-induced cardio-toxicity.
背景/目的：三氧化二砷（AsO）的临床应用受到其心脏毒性的限制。因此，预防 AsO 引起的内皮完整性丧失至关重要。本研究旨在研究 AsO 诱导的内皮功能障碍，并评估西红花酸（crocetin）逆转 AsO 诱导的心脏毒性的效果。
使用培养的人脐静脉内皮细胞（HUVEC）研究 AsO 诱导的氧化应激、细胞凋亡、活性氧（ROS）和 DNA 加合物的产生。此外，评估了西红花酸对 AsO 诱导的心脏毒性的影响。
AsO 降低了 HUVEC 细胞的活力并导致细胞凋亡。此外，AsO 增加了 NADPH 氧化酶活性和细胞内 ROS 水平。此外，AsO 诱导形成了嘧啶二聚体 DNA-糖苷酶和内切酶 III 可消化加合物。西红花酸处理逆转了 AsO 诱导的细胞活力降低、细胞凋亡诱导、NADPH 氧化酶活性、ROS 水平和 DNA 加合物的形成。
西红花酸可预防 AsO 诱导的心脏毒性。
