BDE No 99 是在人体液体和脂肪饮食中检测到的主要多溴二苯醚 (PBDE) 同系物。
BDE No 99 is the predominant Polybrominated diphenyl ethers(PBDE) congeners detected in human fluid and fatty diet. PBDEs are persistent and bio-accumulative in the environment.[1].
BDE No 99 reduced human and murine oligodendrocyte lineage (O4+) cell formation in a concentration-dependent manner (IC50 1.9?μM and 13.6?μM, respectively and IC20 0.9?μM and 6.9?μM, respectively) with human NPCs being 7-times more sensitive towards BDE No 99 exposure than their murine counterparts. BDE No 99 reduced generation of human and mouse O4+ cells, but there is no indication for BDE No 99 interfering with cellular TH signaling during O4+ cell formation. BDE No 99 reduced hMBP expression due to oligodendrocyte reduction, but concentrations that did not affect the number of mouse O4+ cells inhibited TH-induced mMog transcription by a yet unknown mechanism[2]
BDE No 99 increased unconjugated bile acids(BAs) in the serum, liver, small large intestinal contents(SIC) and large intestinal contents(LIC) of conventional mice. BDE No 99 profoundly decreased the alpha diversity of gut microbiome and differentially regulated 45 bacterial species. BDE No 99 downregulated enzymes and transporters involved in BA metabolism, in a gut microbiome-dependent manner[3]
参考文献:
[1]. Frederiksen M, Vorkamp K, et al. Human internal and external exposure to PBDEs--a review of levels and sources. Int J Hyg Environ Health. 2009 Mar;212(2):109-34.
[2]. Dach K, Bendt F, et al. BDE-99 impairs differentiation of human and mouse NPCs into the oligodendroglial lineage by species-specific modes of action. Sci Rep. 2017 Mar 20;7:44861.
[3]. Li CY, Dempsey JL, et al. PBDEs Altered Gut Microbiome and Bile Acid Homeostasis in Male C57BL/6 Mice. Drug Metab Dispos. 2018 Aug;46(8):1226-1240.
BDE No 99 是在人体体液和脂肪饮食中检测到的主要多溴联苯醚 (PBDE) 同系物。 PBDEs 在环境中具有持久性和生物蓄积性。[1]。
BDE No 99 以浓度依赖性方式减少人和鼠少突胶质细胞谱系 (O4+) 细胞形成（IC50 分别为 1.9μM 和 13.6μM，IC20 分别为 0.9μM 和 6.9μM），人类 NPC 的数量是其 7 倍对 BDE No 99 的暴露比他们的小鼠对应物更敏感。 BDE No 99 减少了人和小鼠 O4+ 细胞的生成，但没有迹象表明 BDE No 99 在 O4+ 细胞形成过程中干扰细胞 TH 信号传导。 BDE No 99 由于少突胶质细胞减少而降低了 hMBP 表达，但不影响小鼠 O4+ 细胞数量的浓度通过未知机制抑制了 TH 诱导的 mMog 转录[2]
BDE No 99 增加了常规小鼠血清、肝脏、小肠内容物 (SIC) 和大肠内容物 (LIC) 中的未结合胆汁酸 (BA)。 BDE No 99 显着降低了肠道微生物组的 alpha 多样性，并对 45 种细菌进行了差异调节。 BDE No 99 以肠道微生物组依赖性方式下调参与 BA 代谢的酶和转运体[3]
| Cell experiment [1]: | |
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Cell lines |
Human and mouse neural progenitor cells |
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Preparation Method |
Human mouse neural progenitor cells (NPCs) were differentiated with DMSO or increasing concentrations of BDE No 99 for 5 days. oligodendrocyte lineage cells were immunocytochemically stained with an antibody against O4 and nuclei were counterstained with Hoechst 33258. Viability was measured with the Alamar-Blue assay two hours prior fixation. |
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Reaction Conditions |
0.01 - 20μM BDE No 99 for 5 days. |
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Applications |
BDE No 99 reduces NPC differentiation to the oligodendrocyte (O4+ cells) lineage. BDE No 99 reduced human and murine O4+ cell formation in a concentration-dependent manner with human NPCs being 7-times more sensitive towards BDE No 99 exposure than their murine counterparts. |
| Animal experiment [2]: | |
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Animal models |
C57BL/6J conventional(CV) mice, C57BL/6J germ-free (GN) mice |
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Preparation Method |
CV and GN mice were randomly allocated for the treatment of vehicle (corn oil, 10 ml/kg), or BDE No 99 via oral gavage once daily for 4 days. Livers were collected 24 hours after the last dosing on the fifth day and immediately frozen in liquid nitrogen. The mRNAs of phase-I drug-metabolizing enzymes Cyp1a2 , Cyp2b10, and Cyp3a11 were quantified in livers of CV mice using RT-qPCR. |
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Dosage form |
10, 100 μmol/kg BDE No 99, oral gavage |
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Applications |
Many Cyp2 family members (such as Cyp2a5, Cyp2b10, Cyp2c37, Cyp2c50, Cyp2c54, and Cyp2c55) are upregulated by BDE No 99 in livers of both CV and GF mice, with a much greater fold change observed in GF conditions. |
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参考文献: [1]. Dach K, Bendt F, et al. BDE-99 impairs differentiation of human and mouse NPCs into the oligodendroglial lineage by species-specific modes of action. Sci Rep. 2017 Mar 20;7:44861. [2]. Li CY, Lee S, et al. Novel Interactions between Gut Microbiome and Host Drug-Processing Genes Modify the Hepatic Metabolism of the Environmental Chemicals Polybrominated Diphenyl Ethers. Drug Metab Dispos. 2017 Nov;45(11):1197-1214. |
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