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 Aug 9;27(16):5056. doi: 10.3390/molecules27165056.
(1) Background: 2,4,6-Tribromophenol (2,4,6-TBP) and pentabromophenol (PBP) are utilized as brominated flame retardants (BFRs) in order to reduce the combustion of materials used in various utility products. The presence of 2,4,6-TBP and PBP has been reported in environmental samples as well as in inhaled air, dust, food, drinking water, and the human body. To date, there are limited data concerning the toxic action of 2,4,6-TBP and particularly PBP, and no study has been conducted to assess the apoptotic mechanism of action of these substances in human leukocytes. (2) Methods: PBMCs were isolated from leukocyte-platelet buffy coat and treated with tested substances in concentrations ranging from 0.01 to 50 µg/mL for 24 h. The apoptotic mechanism of action of the tested BFRs was assessed by the determination of phosphatidylserine exposure on the PBMCs surface, the evaluation of mitochondrial potential and cytosolic calcium ion levels, and the determination of caspase-8, -9, and -3 activation. Moreover, poly (ADP-ribose) polymerase-1 (PARP-1) cleavage, DNA fragmentation, and chromatin condensation were analyzed. (3) Results: 2,4,6-TBP and, more strongly, PBP induced apoptosis in PBMCs, changing all tested parameters. It was also found that the mitochondrial pathway was mainly involved in the apoptosis of PBMCs exposed to the studied compounds. (4) Conclusions: 2,4,6-TBP and PBP triggered apoptosis in human PBMCs, and some observed changes occurred at 2,4,6-TBP concentrations that were detected in humans occupationally exposed to this substance.
(1) 背景：2,4,6-三溴苯酚（2,4,6-TBP）和五溴苯酚（PBP）被用作溴化阻燃剂（BFRs），以减少各种实用产品中材料的燃烧。环境样本以及吸入的空气、灰尘、食物、饮用水和人体中都已经报告了 2,4,6-TBP 和 PBP 的存在。迄今为止，关于 2,4,6-TBP 的毒性作用，特别是 PBP 的毒性作用的数据有限，并且没有研究评估这些物质在人白细胞中的凋亡作用机制。(2) 方法：从白细胞-血小板缓冲层中分离 PBMCs，并将其用测试物质处理，浓度范围为 0.01 至 50μg/ml，处理 24 小时。通过测定 PBMCs 表面的磷脂酰丝氨酸暴露、评估线粒体电势和胞浆钙离子水平以及测定 caspase-8、-9 和 -3 的激活来评估测试 BFRs 的凋亡作用机制。此外，还分析了多聚（ADP-核糖）聚合酶-1（PARP-1）的切割、DNA 片段化和染色质凝聚。(3) 结果：2,4,6-TBP 和更强烈的 PBP 诱导 PBMCs 凋亡，改变了所有测试参数。还发现，研究化合物暴露后 PBMCs 的凋亡主要涉及线粒体途径。(4) 结论：2,4,6-TBP 和 PBP 诱导人 PBMCs 凋亡，并且在某些观察到的变化发生在人类职业接触该物质时检测到的 2,4,6-TBP 浓度。
