Study of metabolic disorders associated with BDE-47 exposure in Drosophila model by MS-based metabolomics

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^th 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^th 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.