Department of Environmental Science, Stockholm University, Stockholm, Sweden; Amsterdam Institute for Life and Environment, Vrije Universiteit, Amsterdam, the Netherlands.
Amsterdam Institute for Life and Environment, Vrije Universiteit, Amsterdam, the Netherlands.
Sci Total Environ. 2023 Jan 20;857(Pt 1):159269. doi: 10.1016/j.scitotenv.2022.159269. Epub 2022 Oct 6.
Hydroxylated polybrominated diphenyl ethers (OH-PBDEs) are formed by metabolism from the flame retardants polybrominated diphenyl ethers (PBDEs). In the aquatic environment, they are also produced naturally. OH-PBDEs are known for their potential to disrupt energy metabolism, the endocrine system, and the nervous system. This is the first study focusing on the effects of OH-PBDEs at the metabolite level in vivo. The aim of the current study was to investigate the metabolic effects of exposure to OH-PBDEs using metabolomics, and to identify potential biomarker(s) for energy disruption of OH-PBDEs. Zebrafish (Danio rerio) embryos were exposed to two different concentrations of 6-OH-BDE47 and 6-OH-BDE85 and a mixture of these two compounds. In total, 342 metabolites were annotated and 79 metabolites were affected in at least one exposure. Several affected metabolites, e.g. succinic acid, glutamic acid, glutamine, tyrosine, tryptophan, adenine, and several fatty acids, could be connected to known toxic mechanisms of OH-PBDEs. Several phospholipids were strongly up-regulated with up to a six-fold increase after exposure to 6-OH-BDE47, a scarcely described effect of OH-PBDEs. Based on the observed metabolic effects, a possible connection between disruption of the energy metabolism, neurotoxicity and potential immunotoxicity of OH-PBDEs was suggested. Single compound exposures to 6-OH-BDE47 and 6-OH-BDE85 showed little overlap in the affected metabolites. This shows that compounds of similar chemical structure can induce different metabolic effects, possibly relating to their different toxic mechanisms. There were inter-concentration differences in the metabolic profiles, indicating that the metabolic effects were concentration dependent. After exposure to the mixture of 6-OH-BDE47 and 6-OH-BDE85, a new metabolic profile distinct from the profiles obtained from the single compounds was observed. Succinic acid was up-regulated at the highest, but still environmentally relevant, concentration of 6-OH-BDE47, 6-OH-BDE85, and the mixture. Therefore, succinic acid is suggested as a potential biomarker for energy disruption of OH-PBDEs.
羟基化多溴二苯醚（OH-PBDEs）是由阻燃剂多溴二苯醚（PBDEs）代谢形成的。在水生环境中，它们也自然产生。OH-PBDEs 以其破坏能量代谢、内分泌系统和神经系统的潜力而闻名。这是第一项专注于体内 OH-PBDEs 代谢物水平影响的研究。本研究的目的是使用代谢组学研究暴露于 OH-PBDEs 时的代谢效应，并确定 OH-PBDEs 能量破坏的潜在生物标志物。斑马鱼（Danio rerio）胚胎暴露于两种不同浓度的 6-OH-BDE47 和 6-OH-BDE85 以及这两种化合物的混合物中。总共注释了 342 种代谢物，至少有 79 种代谢物受到影响。一些受影响的代谢物，例如琥珀酸、谷氨酸、谷氨酰胺、酪氨酸、色氨酸、腺嘌呤和几种脂肪酸，可与 OH-PBDEs 的已知毒性机制联系起来。暴露于 6-OH-BDE47 后，几种磷脂强烈上调，上调幅度高达六倍，这是 OH-PBDEs 的一种鲜为人知的作用。基于观察到的代谢效应，提出了 OH-PBDEs 破坏能量代谢、神经毒性和潜在免疫毒性之间的可能联系。单化合物暴露于 6-OH-BDE47 和 6-OH-BDE85 显示出受影响代谢物的很少重叠。这表明具有相似化学结构的化合物可以诱导不同的代谢效应，这可能与其不同的毒性机制有关。代谢谱存在浓度间差异，表明代谢效应与浓度有关。暴露于 6-OH-BDE47 和 6-OH-BDE85 的混合物后，观察到一种与单化合物获得的谱不同的新代谢谱。琥珀酸在最高浓度（但仍处于环境相关浓度）的 6-OH-BDE47、6-OH-BDE85 和混合物中上调。因此，琥珀酸被建议作为 OH-PBDEs 能量破坏的潜在生物标志物。
