Su Chun-Hung, Chen Shih-Pin, Chen Li-You, Yang Jiann-Jou, Lee Yi-Chia, Lee Shiuan-Shinn, Chen Hsin-Hung, Ng Yan-Yan, Kuan Yu-Hsiang
Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC; Department of Internal Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC; Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC.
Department of Internal Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC; Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC.
Ecotoxicol Environ Saf. 2021 Nov 11;228:112962. doi: 10.1016/j.ecoenv.2021.112962.
Fluoranthene, a high-molecular-weight polycyclic aromatic hydrocarbon (PAH), is widely present in air pollutants, including fine inhalable particulate matter. 3-Bromofluoranthene (3-BrFlu), which is a brominated fluoranthene and halogenated PAH, is generated from waste combustion, metallurgical processes, cement production, e-waste dismantling, and photoreaction. Vascular endothelial cells have key functions in the homeostasis and the development of the cardiovascular system. The zebrafish model has been widely employed to study cardiotoxicity and embryotoxicity. However, no evidence has indicated that 3-BrFlu induces cytotoxicity in vascular endothelial cells, or cardiotoxicity and embryotoxicity in zebrafish. In this study, 3-BrFlu induced concentration-dependent changes in embryo- and cardiotoxicity. Cytotoxicity was also induced by 3-BrFlu in a concentration-dependent manner through apoptosis and necrosis in vascular endothelial cells, SVEC4-10 cells. The activities of caspase-3, -8, and -9 were induced by 3-BrFlu via an intrinsic pathway constituting Bcl-2 downregulation, Bad upregulation, and mitochondrial dysfunction; the extrinsic pathway included the expression of death receptors, including tumour necrosis factor α and Fas receptors. These results indicated that 3-BrFlu caused cardio- and embryotoxicity in zebrafish through vascular endothelial cells cytotoxicity resulting from caspase-dependent apoptosis through intrinsic and extrinsic pathways.
荧蒽是一种高分子量多环芳烃（PAH），广泛存在于空气污染物中，包括可吸入细颗粒物。3-溴荧蒽（3-BrFlu）是一种溴化荧蒽和卤代多环芳烃，产生于废物燃烧、冶金过程、水泥生产、电子废物拆解和光化学反应。血管内皮细胞在心血管系统的稳态和发育中起关键作用。斑马鱼模型已被广泛用于研究心脏毒性和胚胎毒性。然而，尚无证据表明3-BrFlu会诱导血管内皮细胞产生细胞毒性，或在斑马鱼中引发心脏毒性和胚胎毒性。在本研究中，3-BrFlu诱导了胚胎毒性和心脏毒性的浓度依赖性变化。3-BrFlu还通过诱导血管内皮细胞SVEC4-10细胞凋亡和坏死，以浓度依赖性方式诱导细胞毒性。3-BrFlu通过构成Bcl-2下调、Bad上调和线粒体功能障碍的内在途径诱导caspase-3、-8和-9的活性；外在途径包括死亡受体的表达，如肿瘤坏死因子α和Fas受体。这些结果表明，3-BrFlu通过内在和外在途径依赖caspase的凋亡导致血管内皮细胞毒性，从而在斑马鱼中引起心脏毒性和胚胎毒性。
