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.

中文翻译：

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HBCD、TBECH 和 BTBPE 通过调节线粒体功能和 ROS 产生对人血管内皮细胞表现出细胞毒性作用

溴化阻燃剂 (BFR)，例如 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 1,2-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 在人血管内皮细胞 (EC) 中的毒性。数据显示六溴环十二烷、TBECH 和 BTBPE 诱导细胞毒性，即剂量依赖性细胞活力降低、细胞膜通透性和细胞凋亡增加、迁移和管腔形成抑制。此外，发现六溴环十二烷比 BTBPE 或 TBECH 的毒性更大。暴露于 HBCD、TBECH 和 BTBPE 导致活性氧的产生、线粒体超氧化物的生成和线粒体膜电位崩溃，暗示反应性应激导致细胞毒性。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导致细胞凋亡的关键机制。本研究表明，线粒体是内皮细胞中 BFR 的新靶点，并进一步加深了我们对 BFR 发育毒性的理解。