Metabolomic Research On Early BDE-47 Exposure To Mice

BDE-47 is a widespread persistent organic pollutants in the environment, it has the effects of endocrine disrupting, neural toxicity, immune toxicity and some other toxiticies. Researches on the toxicities of BDE-47 mainly focused on single toxicity except from its comprehensive toxicity. Metabolomic can be used in the research on comprehensive toxicity of BDE-47. Metabolomics is a part of system biology, it analyses the impact of external stimuli to the body by providing the information of small endogenous metabolites (molecular weight< 1000) changes, and it is in primary stage. Using the method of metabolomics to analysis BDE-47 toxic effect on organism, getting its potential biomarkers is an effective approach to study its toxic mechanism. The neurotoxicity study showed that BDE-47’s effect on baby are more obvious and BDE-47 has a potential effect on baby mice, when the baby mice grow up, the adult will be effectd on its neuroethology. In the research Balb/c mice was used as the model animal to investigate the metabolomic effects of BDE-47 on brain tissue, blood and urine by LC/MS/MS technology. Mice were exposured toBDE-47 under low, medium and high concentration each for 28 days and then were divided into two groups. One group was analysed by metabolomic method directly and the other group did the same after a three-month normal breeding. After data discriminant analyzing and the statistical testing, we can get the biomarkers of each group and analyze the metabolic pathway based on the change of the metabolites. At the same time in order to study whether the BDE - 47 has reached the target organs, concentration of BDE-47 in the brains tissues of two groups were determined, and we also improved the LC/MS/MS instrument method for determination of some metabolites of small molecules.The results show that in the early subchronic exposure BDE-47 can be enriched in the mice brain. The higher the exposure concentration is the higher BDE-47 level is in the brain. In the second group BDE-47 in all groups were lower than detection limit, which may be caused by the transformation of BDE-47 to hydroxylation PBDEs, or by excreting through the feces and urine.Metabolomic research on the brain tissue, plasma and urine of the mice showed that early subchronic exposure of BDE-47 can affect the metabolism of mice. And the disorder still exists in the second group with different biomarkers, which indicated different toxic mechanisms of the two periods. The brain metabolomic result showed brain neurotransmitter like gamma-aminobutyric acid, dopamine, norepinephrine and serotonin synthesis are affected by the BDE-47 exposure.BDE-47 exposure can lead to a rise in concentration of dopamine increase and norepinephrine decrease. The beta dopamine hydroxylase was inhibited by BDE-47. The metabolite pathway analysis showed that BDE -47 exposure can affect phospholipid in the brain, plasma and urine, thereby affect the glycerol phospholipid metabolite pathways. Metabolic pathway analysis result also showed the synthesis of amino acids were also affected.