State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China.
State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong, China; SUSTech Academy for Advanced Interdisciplinary Studies, Southern University of Science and Technology, Shenzhen, China.
Ecotoxicol Environ Saf. 2019 Nov 30;184:109606. doi: 10.1016/j.ecoenv.2019.109606. Epub 2019 Aug 28.
Epidemiological and animal studies have revealed a possible linkage between 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) exposure and neurodegenerative disease such as Parkinson's disease (PD). However, whether or how BDE-47 would affect the PD progression remains unclear. Here, we carried out a metabolomics study based on liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) to investigate the possible contribution of BDE-47 exposure to PD progression in Drosophila (fly) model. Transgenic PD flies were exposed to BDE-47 through diet for 30 days. Global metabolomic analysis identified 48 altered metabolites after the exposure. These metabolites were mainly involved in tryptophan metabolism, phenylalanine metabolism, purine metabolism, and alanine, aspartate and glutamate metabolism. Further, by quantifying metabolites of interest using LC-MS/MS, we confirmed that the formation of neuro-protector kynurenic acid was slowed down while the formation of neurotoxin 3-hydroxy-kynurenine was speeded up on the 20 exposure day. Moreover, the levels of SAM/SAH (an index of methylation potential) and GSH/GSSG (an indicator of oxidative stress) were found to decrease on the 30 exposure day. Our results suggest that BDE-47 could induce imbalance of kynurenine metabolism and methylation potential, and oxidative stress, which might further accelerate PD progression.
流行病学和动物研究表明,2,2',4,4'-四溴二苯醚 (BDE-47) 暴露与神经退行性疾病(如帕金森病 (PD))之间可能存在联系。然而,BDE-47 是否会影响 PD 的进展以及如何影响仍不清楚。在这里,我们进行了一项基于液相色谱-质谱 (LC-MS) 和气相色谱-质谱 (GC-MS) 的代谢组学研究,以调查 BDE-47 暴露对果蝇 (苍蝇) 模型中 PD 进展的可能贡献。转基因 PD 苍蝇通过饮食暴露于 BDE-47 30 天。全局代谢组学分析确定暴露后有 48 种代谢物发生改变。这些代谢物主要涉及色氨酸代谢、苯丙氨酸代谢、嘌呤代谢以及丙氨酸、天冬氨酸和谷氨酸代谢。此外,通过使用 LC-MS/MS 定量感兴趣的代谢物,我们证实神经保护剂犬尿氨酸的形成速度减慢,而神经毒素 3-羟基犬尿氨酸的形成速度加快。此外,在暴露 30 天后,SAM/SAH(甲基化潜力的指标)和 GSH/GSSG(氧化应激的指标)的水平发现下降。我们的结果表明,BDE-47 可能会导致犬尿氨酸代谢和甲基化潜力以及氧化应激失衡,这可能进一步加速 PD 的进展。