Shanghai East Hospital, Key Laboratory of Yangtze River Water Environment Ministry of Education, College of Environmental Science and Engineering, Tongji University, Shanghai, China.
Division of Cardiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Environ Toxicol. 2021 Aug;36(8):1674-1682. doi: 10.1002/tox.23163. Epub 2021 May 11.
Brominated flame retardants (BFRs), such as, 1,2,5,6-tetrabromocyclooctane (HBCD), 1,2-dibromo-4-(1,2-dibromopropyl)cyclohexane (TBECH), and 1 1,2-bis-(2,4,6-tribromophenoxy)ethane (BTBPE), have garnered increasing attention due to their potent biological effects. In the present study, the toxicity of HBCD, TBECH, and BTBPE in human vascular endothelial cells (ECs) was explored. The data showed that HBCD, TBECH, and BTBPE induced cytotoxicity, namely dose-dependent cell viability reduction, cell membrane permeability and apoptosis increase, migration, and lumen formation inhibition. Moreover, HBCD was found to be more toxic than BTBPE or TBECH. Exposure to HBCD, TBECH, and BTBPE led to the production of reactive oxygen species, mitochondrial superoxide generation, and mitochondrial membrane potential collapse, implying that reactive stress caused the cytotoxicity. The ATP content, glutathione content, superoxide dismutase, and MDA activities were reduced, indicating that mitochondrial dysfunction may be the key mechanisms responsible for apoptosis. The present study suggested that mitochondria are a new target of BFRs in ECs and further deepened our understanding of the developmental toxicity of BFRs.
溴系阻燃剂（BFRs），如 1,2,5,6-四溴环辛烷（HBCD）、1,2-二溴-4-（1,2-二溴丙基）环己烷（TBECH）和 1,1,2-双-（2,4,6-三溴苯氧基）乙烷（BTBPE），由于其强大的生物效应而受到越来越多的关注。在本研究中，探讨了 HBCD、TBECH 和 BTBPE 对人血管内皮细胞（ECs）的毒性。结果表明，HBCD、TBECH 和 BTBPE 诱导细胞毒性，即剂量依赖性细胞活力降低、细胞膜通透性增加和凋亡增加、迁移和管腔形成抑制。此外，HBCD 的毒性比 BTBPE 或 TBECH 更强。暴露于 HBCD、TBECH 和 BTBPE 导致活性氧的产生、线粒体超氧化物的产生和线粒体膜电位的崩溃，表明活性应激导致了细胞毒性。ATP 含量、谷胱甘肽含量、超氧化物歧化酶和 MDA 活性降低，表明线粒体功能障碍可能是细胞凋亡的关键机制。本研究表明，线粒体是 BFRs 在 ECs 中的一个新靶标，进一步加深了我们对 BFRs 发育毒性的理解。
