Miller I, Serchi T, Cambier S, Diepenbroek C, Renaut J, Van der Berg J H J, Kwadijk C, Gutleb A C, Rijntjes E, Murk A J
Institute for Medical Biochemistry, Department for Biomedical Sciences, University of Veterinary Medicine Vienna, Veterinaerplatz 1, A-1210 Vienna, Austria.
Environmental Research and Innovation (ERIN) Department, Luxembourg Institute of Science and Technology (LIST), 5, Avenue des Hauts-Forneaux, L-4362 Esch-sur-Alzette, Luxembourg.
Toxicol Lett. 2016 Mar 14;245:40-51. doi: 10.1016/j.toxlet.2016.01.002. Epub 2016 Jan 12.
Hexabromocyclododecane (HBCD) is a brominated flame retardant known for its low acute toxicity as observed in animal experiments. However, HBCD exposure can affect liver functioning and thyroid hormone (TH) status. As exact mechanisms are unknown and only limited toxicological data exists, a gel-based proteomic approach was undertaken. In a eu- and hypothyroid female rat model, rats were exposed to 3 and 30 mg/kg bw/day HBCD for 7 days via their diet, and exposure was related to a range of canonical endpoints (hormone status, body weight) available for these animals. Alterations in the liver proteome under HBCD exposure were determined in comparison with patterns of control animals, for both thyroid states. This revealed significantly changed abundance of proteins involved in metabolic processes (gluconeogenesis/glycolysis, amino acid metabolism, lipid metabolism), but also in oxidative stress responses, in both euthyroid and hypothyroid rats. The results provide a more detailed picture on the mechanisms involved in these alterations, e.g. at the protein level changes of the proposed influence of HBCD on the lipid metabolism. Present results show that proteomic approaches can provide further mechanistic insights in toxicological studies.
六溴环十二烷（HBCD）是一种溴化阻燃剂，在动物实验中其急性毒性较低。然而，接触HBCD会影响肝脏功能和甲状腺激素（TH）状态。由于确切机制尚不清楚且毒理学数据有限，因此采用了基于凝胶的蛋白质组学方法。在正常甲状腺和甲状腺功能减退的雌性大鼠模型中，大鼠通过饮食以3和30 mg/kg体重/天的剂量接触HBCD，持续7天，且接触与这些动物可用的一系列标准终点（激素状态、体重）相关。针对两种甲状腺状态，将接触HBCD的大鼠肝脏蛋白质组的变化与对照动物的模式进行比较来确定。这表明，在正常甲状腺和甲状腺功能减退的大鼠中，参与代谢过程（糖异生/糖酵解、氨基酸代谢、脂质代谢）以及氧化应激反应的蛋白质丰度发生了显著变化。结果提供了关于这些变化所涉及机制的更详细情况，例如在蛋白质水平上HBCD对脂质代谢的拟议影响的变化。目前的结果表明，蛋白质组学方法可以为毒理学研究提供进一步的机制见解。
