Organophosphorus flame retardants are developmental neurotoxicants in a rat primary brainsphere in vitro model.
Organophosphorus flame retardants are developmental neurotoxicants in a rat primary brainsphere in vitro model.
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DOI：
10.1007/s00204-020-02903-2
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发表时间：
2021-01
影响因子：
6.1
通讯作者：
Hartung T
中科院分区：
文献类型：
--
作者：
Hogberg HT;de Cássia da Silveira E Sá R;Kleensang A;Bouhifd M;Cemiloglu Ulker O;Smirnova L;Behl M;Maertens A;Zhao L;Hartung T
由于监管禁令和自愿替代，卤代多溴二苯醚(PBDE)阻燃剂(FR)正越来越多地被主要有机磷阻燃剂(OPFR)取代。利用3D大鼠原代神经器官型体外模型(大鼠脑)，我们比较了BDE-47-最丰富的PBDE同系物-与四种OPFR(异丙基苯基磷酸盐-IPP、三苯基磷酸盐-TPHP、异癸基二苯基磷酸盐-IDDP和三甲基苯基磷酸盐)-TMPP的发育神经毒性效应。利用基于质谱学的代谢组学和转录组学，我们观察到在与人类相关的非细胞毒性浓度相似的情况下(0.1-5微米)，OPFR具有更强的发育神经毒性作用。这包括对低微米范围内的神经元的毒性；所有FR都会降低神经递质谷氨酸和GABA(除BDE-47和TPHP外)。此外，被认为是神经学诊断分子的N-乙酰天冬氨酸(NAA)被所有OPFR降低。在相似的浓度下，目前使用的FR降低了质膜多巴胺活性转运体的表达，而BDE-47没有。一些发现表明，星形胶质细胞增生症是由OPFR引起的，而不是BDE-47。在5µM浓度下，OPFR对髓鞘形成的干扰大于BDE-47。细胞因子基因和受体表达的增加表明，暴露于OPFR可能会诱导炎症反应。途径/类别的过度表达在1)动作电位传递、细胞-细胞信号传递、突触传递、受体信号传递、(2)免疫反应、炎症、防御反应、(3)细胞周期和(4)脂质代谢和运输方面表现出干扰。综上所述，这似乎是一个令人遗憾的案例，在原始的大鼠3D模型中，用不降低发育神经毒性的物质替代了这些物质。本文的在线版本(10.1007/s00204-020-02903-2)包含向授权用户提供的补充材料。
Due to regulatory bans and voluntary substitutions, halogenated polybrominated diphenyl ether (PBDE) flame retardants (FR) are increasingly substituted by mainly organophosphorus FR (OPFR). Leveraging a 3D rat primary neural organotypic in vitro model (rat brainsphere), we compare developmental neurotoxic effects of BDE-47—the most abundant PBDE congener—with four OPFR (isopropylated phenyl phosphate—IPP, triphenyl phosphate—TPHP, isodecyl diphenyl phosphate—IDDP, and tricresyl phosphate (also known as trimethyl phenyl phosphate)—TMPP). Employing mass spectroscopy-based metabolomics and transcriptomics, we observe at similar human-relevant non-cytotoxic concentrations (0.1–5 µM) stronger developmental neurotoxic effects by OPFR. This includes toxicity to neurons in the low µM range; all FR decrease the neurotransmitters glutamate and GABA (except BDE-47 and TPHP). Furthermore, n-acetyl aspartate (NAA), considered a neurologic diagnostic molecule, was decreased by all OPFR. At similar concentrations, the FR currently in use decreased plasma membrane dopamine active transporter expression, while BDE-47 did not. Several findings suggest astrogliosis induced by the OPFR, but not BDE-47. At the 5 µM concentrations, the OPFR more than BDE-47 interfered with myelination. An increase of cytokine gene and receptor expressions suggests that exposure to OPFR may induce an inflammatory response. Pathway/category overrepresentation shows disruption in 1) transmission of action potentials, cell–cell signaling, synaptic transmission, receptor signaling, (2) immune response, inflammation, defense response, (3) cell cycle and (4) lipids metabolism and transportation. Taken together, this appears to be a case of regretful substitution with substances not less developmentally neurotoxic in a primary rat 3D model. The online version of this article (10.1007/s00204-020-02903-2) contains supplementary material, which is available to authorized users.
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影响因子：
4.7
作者：
Burke RD;Todd SW;Lumsden E;Mullins RJ;Mamczarz J;Fawcett WP;Gullapalli RP;Randall WR;Pereira EFR;Albuquerque EX
通讯作者：
Albuquerque EX
DOI：
10.14573/altex.1406111
发表时间：
2014
期刊：
ALTEX
影响因子：
--
作者：
Alépée N;Bahinski A;Daneshian M;De Wever B;Fritsche E;Goldberg A;Hansmann J;Hartung T;Haycock J;Hogberg H;Hoelting L;Kelm JM;Kadereit S;McVey E;Landsiedel R;Leist M;Lübberstedt M;Noor F;Pellevoisin C;Petersohn D;Pfannenbecker U;Reisinger K;Ramirez T;Rothen-Rutishauser B;Schäfer-Korting M;Zeilinger K;Zurich MG
通讯作者：
Zurich MG
影响因子：
2.5
作者：
BARBIN, G;POLLARD, H;BENARI, Y
通讯作者：
BENARI, Y
溴化阻燃剂：值得关注吗？
影响因子：
10.4
作者：
Birnbaum LS;Staskal DF
通讯作者：
Staskal DF
DOI：
10.1186/1476-069x-7-50
发表时间：
2008-10-22
期刊：
Environmental health : a global access science source
影响因子：
--
作者：
Bjørling-Poulsen M;Andersen HR;Grandjean P
通讯作者：
Grandjean P