The brominated flame retardant BDE-47 causes oxidative stress and apoptotic cell death in vitro and in vivo in mice.
The brominated flame retardant BDE-47 causes oxidative stress and apoptotic cell death in vitro and in vivo in mice.
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DOI：
10.1016/j.neuro.2015.03.008
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发表时间：
2015-05
期刊：
影响因子：
3.4
通讯作者：
Roque, Pamela J.
中科院分区：
文献类型：
--
作者：
Costa, Lucio G.;Pellacani, Claudia;Dao, Khoi;Kavanagh, Terrance J.;Roque, Pamela J.
多溴联苯醚（PBDEs）作为阻燃剂使用了几十年，现已成为广泛的环境污染物。据信，接触主要通过饮食和灰尘发生，婴儿和幼儿的身体负担最高，引起了对潜在发育神经毒性的关注。多溴二苯醚神经毒性的确切机制尚未阐明，但有两种相关的作用模式涉及甲状腺激素体内平衡受损和对脑细胞的直接影响，导致信号转导、氧化应激和细胞凋亡的改变。本研究表明，BDE-47（2，2 ′，4，4 ′-四溴二苯醚）在体外诱导小鼠小脑颗粒神经元的氧化应激和随后的细胞凋亡。同样，根据一项暴露方案，体内施用BDE-47可引起行为和生化变化（10毫克/千克，出生后第10天经口），可引起氧化应激和细胞凋亡，而不会改变甲状腺激素的血清水平。BDE-47在体外和体内的影响在缺乏谷氨酸半胱氨酸连接酶（GCLM）修饰亚基的小鼠模型中更为明显，由于GSH水平低，导致抗氧化能力降低。BDE-47在大脑中的浓度为中纳摩尔。这些研究结果表明，在体外观察到的BDE-47效应在体内给药后也存在，这表明，除了潜在的内分泌效应（在此未观察到）外，与脑细胞的直接相互作用应被视为BDE-47神经毒性的潜在机制。
Polybrominated diphenyl ethers (PBDEs), used for decades as flame retardants, have become widespread environmental contaminants. Exposure is believed to occur primarily through diet and dust, and infants and toddlers have the highest body burden, raising concern for potential developmental neurotoxicity. The exact mechanisms of PBDE neurotoxicity have not been elucidated, but two relevant modes of action relate to impairment of thyroid hormone homeostasis and to direct effects on brain cells causing alterations in signal transduction, oxidative stress and apoptotic cell death. The present study shows that BDE-47 (2,2′,4,4′-tetrabromodiphenyl ether) induces oxidative stress and ensuing apoptotic cell death in mouse cerebellar granule neurons in vitro. Similarly, in vivo administration of BDE-47, according to an exposure protocol shown to induce behavioral and biochemical alterations (10 mg/kg, per os on post-natal day 10), induces oxidative stress and apoptosis, without altering serum levels of thyroid hormones. The effects of BDE-47 both in vitro and in vivo were more pronounced in a mouse model lacking the modifier subunit of glutamate cysteine ligase (GCLM) which results in reduced anti-oxidant capability due to low levels of GSH. Concentrations of BDE-47 in brain were in the mid-nanomolar range. These findings indicate that effects observed with BDE-47 in vitro are also present after in vivo administration, suggesting that in addition to potential endocrine effects, which were not seen here, direct interactions with brain cells should be considered as a potential mechanism of BDE-47 neurotoxicity.
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影响因子：
10.4
作者：
Herbstman JB;Sjödin A;Kurzon M;Lederman SA;Jones RS;Rauh V;Needham LL;Tang D;Niedzwiecki M;Wang RY;Perera F
通讯作者：
Perera F
影响因子：
10.4
作者：
Herbstman JB;Sjödin A;Apelberg BJ;Witter FR;Halden RU;Patterson DG;Panny SR;Needham LL;Goldman LR
通讯作者：
Goldman LR
影响因子：
2.6
作者：
Gee, Jillian R.;Moser, Virginia C.;Herr, David W.
通讯作者：
Herr, David W.
影响因子：
3.8
作者：
Giordano, Gennaro;White, Collin C.;Costa, Lucio G.
通讯作者：
Costa, Lucio G.
影响因子：
3.8
作者：
Dingemans, Milou M. L.;van den Berg, Martin;Westerink, Remco H. S.
通讯作者：
Westerink, Remco H. S.