3-Bromofluoranthene-induced cardiotoxicity of zebrafish and apoptosis in the vascular endothelial cells via intrinsic and extrinsic caspase-dependent pathways

Chun-Hung Su; Shih-Pin Chen; Li-You Chen; Jiann-Jou Yang; Yi-Chia Lee; Shiuan-Shinn Lee; Hsin-Hung Chen; Yan-Yan Ng; Yu-Hsiang Kuan

doi:10.1016/j.ecoenv.2021.112962

3-Bromofluoranthene-induced cardiotoxicity of zebrafish and apoptosis in the vascular endothelial cells via intrinsic and extrinsic caspase-dependent pathways

Ecotoxicol Environ Saf. 2021 Nov 11:228:112962. doi: 10.1016/j.ecoenv.2021.112962. Online ahead of print.

Authors

Chun-Hung Su¹, Shih-Pin Chen², Li-You Chen³, Jiann-Jou Yang⁴, Yi-Chia Lee⁵, Shiuan-Shinn Lee⁶, Hsin-Hung Chen⁷, Yan-Yan Ng⁸, Yu-Hsiang Kuan⁹

Affiliations

¹ 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.
² 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.
³ Department of Anatomy, School of Medicine, College of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC; Department of Medical Education, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC.
⁴ Department of BioMedical Sciences, Chung Shan Medical University, Taichung, Taiwan, ROC; Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC.
⁵ Department of Pharmacology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC; Department of Pharmacy, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC.
⁶ School of Public Health, Chung Shan Medical University, Taichung, Taiwan, ROC.
⁷ Division of Endocrinology and Metabolism, Department of Internal Medicine, Asia University Hospital, Taichung, Taiwan, ROC; School of Medicine, Institute of Medicine and public health, Chung Shan Medical University, Taichung, Taiwan, ROC; Chung Sheng Clinic, Nantou, Taiwan, ROC.
⁸ Department of Pediatric, Chung Kang branch, Cheng Ching Hospital, Taichung City, Taiwan, ROC.
⁹ Department of Pharmacology, School of Medicine, Chung Shan Medical University, Taichung, Taiwan, ROC; Department of Pharmacy, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC. Electronic address: kuanyh@csmu.edu.tw.

PMID: 34775346
DOI: 10.1016/j.ecoenv.2021.112962

Abstract

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.

Keywords: 3-Bromofluoranthene; Caspase-dependent apoptosis; Vascular endothelial cells; Zebrafish.