HBCD, TBECH, and BTBPE exhibit cytotoxic effects in human vascular endothelial cells by regulating mitochondria function and ROS production

Abstract

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.

Astragaloside IV protects against oxidized low‐density lipoprotein‐induced injury in human umbilical vein endothelial cells via the histone deacetylase 9 (HDAC9)/NF‐κB axis

“…Additionally, acrolein could cause cell toxicity in HUVECs through regulating cell apoptosis, DNA damage response, and oxidative stress 35 . It was proved that brominated flame retardants induced call damage of HUVECs via modulating ROS production and mitochondria function 36 …”

“…35 It was proved that brominated flame retardants induced call damage of HUVECs via modulating ROS production and mitochondria function. 36 ASV has extensive activities on the hematopoietic system, liver, endocrine system, nervous system, collagen metabolism, cardiac function, and organ immune system. 37 For example, ASV showed the inhibition influence on anti-apoptotic signaling and enhancement on apoptosis in hepatocellular carcinoma.…”

Interactions of Brominated Flame Retardants with Membrane Models of Dehalogenating Bacteria: Langmuir Monolayer and Grazing Incidence X-ray Diffraction Studies

“…BTBPE is one of the most commonly used novel BFRs, applied especially in all these plastics, where PBDEs were previously used. Similar to HBCD and TBCO, BTBPE exhibits cytotoxicity and can damage plasma membranes . TBP is produced in quantities of 10 to 100 tons yearly and applied as novel BFR in some plastics .…”

“…Similar to HBCD and TBCO, BTBPE exhibits cytotoxicity and can damage plasma membranes. 47 TBP is produced in quantities of 10 to 100 tons yearly and applied as novel BFR in some plastics. 45 Moreover, TBP is a BFR of special environmental concern, as it is also a degradation product of multiple other BFRs, to name only PBDEs or BTBPE.…”

Determination of Hexabromocyclododecane in Expanded Polystyrene and Extruded Polystyrene Foam by Gas Chromatography-Mass Spectrometry

“…Also, HBCD has been detected in arctic regions [ 7 ] and breast milk [ 8 ]. There is global concern about the potential toxic effects of HBCD on humans and ecosystems [ 3 , 9 ] because of its persistence in the environment, bioaccumulation, and bioamplification in fish [ 10 ], birds [ 11 ], and mammals [ 12 , 13 ]. Recently many studies in animals have shown that HBCD can affect the expression of related genes in rats [ 14 ] and zebrafish [ 10 ].…”