Department of Biophysics of Environmental Pollution, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska Str. 141/143, 90-236 Lodz, Poland.
Molecules. 2022 Sep 16;27(18):6052. doi: 10.3390/molecules27186052.
Tetrabromobisphenol A (TBBPA) is the most commonly used brominated flame retardant (BFR) in the industry. TBBPA has been determined in environmental samples, food, tap water, dust as well as outdoor and indoor air and in the human body. Studies have also shown the toxic potential of this substance. In search of a better and less toxic BFR, tetrabromobisphenol S (TBBPS) has been developed in order to replace TBBPA in the industry. There is a lack of data on the toxic effects of TBBPS, while no study has explored apoptotic mechanism of action of TBBPA and TBBPS in human leukocytes.
The cells were separated from leucocyte-platelet buffy coat and were incubated with studied compounds in concentrations ranging from 0.01 to 50 µg/mL for 24 h. In order to explore the apoptotic mechanism of action of tested BFRs, phosphatidylserine externalization at cellular membrane (the number of apoptotic cells), cytosolic calcium ion and transmembrane mitochondrial potential levels, caspase-8, -9 and -3 activation, as well as PARP-1 cleavage, DNA fragmentation and chromatin condensation in PBMCs were determined.
TBBPA and TBBPS triggered apoptosis in human PBMCs as they changed all tested parameters in the incubated cells. It was also observed that the mitochondrial pathway was mainly involved in the apoptotic action of studied compounds.
It was found that TBBPS, and more strongly TBBPA, triggered apoptosis in human PBMCs. Generally, the mitochondrial pathway was involved in the apoptotic action of tested compounds; nevertheless, TBBPS more strongly than TBBPA caused intrinsic pathway activation.
四溴双酚 A（TBBPA）是工业中最常用的溴化阻燃剂（BFR）。TBBPA 已在环境样品、食品、自来水、灰尘以及室外和室内空气中以及人体中被检测到。研究还表明了这种物质的毒性潜力。为了寻找更好、毒性更小的 BFR，开发了四溴双酚 S（TBBPS）以取代工业中的 TBBPA。目前缺乏关于 TBBPS 毒性影响的数据，而尚无研究探讨 TBBPA 和 TBBPS 在人白细胞中的凋亡作用机制。
从白细胞-血小板缓冲层中分离出细胞，并将其与研究化合物在 0.01 至 50 µg/mL 的浓度下孵育 24 小时。为了探讨测试的 BFR 引起凋亡的作用机制，检测了细胞膜上的磷脂酰丝氨酸外翻（凋亡细胞数量）、细胞质钙离子和跨膜线粒体膜电位水平、caspase-8、-9 和 -3 的激活以及 PBMCs 中的 PARP-1 裂解、DNA 片段化和染色质浓缩。
TBBPA 和 TBBPS 可改变孵育细胞中的所有测试参数，从而在人 PBMCs 中引发凋亡。还观察到线粒体途径主要参与了研究化合物的凋亡作用。
研究发现 TBBPS 和 TBBPA 均可引发人 PBMCs 凋亡。通常，线粒体途径参与了测试化合物的凋亡作用；然而，TBBPS 比 TBBPA 更强烈地引起内在途径的激活。
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