...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Toxicological sciences: An official journal of the Society of Toxicology >The role of mitochondrial and oxidative injury in BDE 47 toxicity to human fetal liver hematopoietic stem cells.
【24h】

The role of mitochondrial and oxidative injury in BDE 47 toxicity to human fetal liver hematopoietic stem cells.

机译：线粒体和氧化损伤在BDE 47对人胎肝造血干细胞的毒性中的作用。

获取原文
获取原文并翻译 | 示例
   

获取外文期刊封面封底 >>

       
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The polybrominated diphenyl ethers (PBDEs) are a group of flame retardants whose residues have markedly increased in the environment and in human tissues during the last decade. Of the various congeners, BDE 47 (2,2',4,4'-tetrabromodiphenyl ether) is typically the predominant congener observed in fish and wildlife samples, as well as in human tissues. Several studies indicate in utero transfer of PBDEs during pregnancy with residues accumulating in fetal tissues, and thus the potential for BDE 47-mediated injury in utero is of concern. In this study, we examined the mechanisms of BDE 47-mediated injury to primary human fetal liver hematopoietic stem cells (HSCs), which comprise a large proportion of fetal hepatic cells and play a key role in hematopoiesis during fetal development. Incubation of fetal liver HSCs with BDE 47 led to a loss of mitochondrial membrane potential and the onset of apoptosis. These effects were observed in the low micromolar range of BDE 47 exposures. At higher concentrations, BDE 47 elicited a loss of viability, which was accompanied by the generation of reactive oxygen species and peroxidation of HSC lipids. Preincubation of fetal liver HSCs with N-acetylcysteine, a glutathione (GSH) precursor, caused an increase in cellular GSH concentrations, restored mitochondrial redox status, and ameliorated the toxicity of BDE 47. BDE 47-mediated cytotoxicity or oxidative injury was not evident at the lower concentrations (< 1microM). Collectively, these data support a role for oxidative stress in the cytotoxicity of BDE 47 and indicate that oxidative stress-associated biomarkers may be useful in assessing the sublethal effects of BDE 47 toxicity in other models. However, the fact that BDE 47 undergoes a concentration-dependent accumulation in other primary cells in media that can underestimate cellular concentrations (W. R. Mundy et al., 2004, Toxicol. Sci. 82, 164-169) suggests that the HSC cell injury observed in our study may be of less relevance to human in utero PBDE exposures.
机译：多溴二苯醚（PBDEs）是一组阻燃剂，其残留物在过去十年中在环境和人体组织中显着增加。在各种同源物中，BDE 47（2,2'，4,4'-四溴二苯醚）通常是在鱼类和野生生物样品以及人体组织中观察到的主要同源物。多项研究表明，怀孕期间PBDEs在子宫内的转移会在胎儿组织中积累残留物，因此，BDE 47介导的子宫内损伤的可能性值得关注。在这项研究中，我们检查了BDE 47介导的原代人胎肝造血干细胞（HSC）损伤的机制，该干细胞包含大量胎儿肝细胞，并且在胎儿发育过程中在造血过程中起关键作用。胎儿肝HSC与BDE 47的孵育导致线粒体膜电位的丧失和凋亡的开始。在低微摩尔浓度的BDE 47暴露中观察到了这些影响。在较高浓度下，BDE 47引起活力丧失，并伴有活性氧的生成和HSC脂质的过氧化。胎儿肝脏HSC与谷胱甘肽（GSH）前体N-乙酰半胱氨酸的预孵育导致细胞GSH浓度增加，线粒体氧化还原状态恢复，并减轻了BDE 47的毒性。BDE47介导的细胞毒性或氧化损伤在较低的浓度（<1microM）。总体而言，这些数据支持氧化应激在BDE 47的细胞毒性中的作用，并表明与氧化应激相关的生物标记物可能在其他模型中可用于评估BDE 47毒性的亚致死作用。但是，BDE 47在其他原代细胞中在培养基中会发生浓度依赖性积累，这一事实会低估细胞浓度（WR Mundy等，2004，Toxicol。Sci。82，164-169），这表明观察到了HSC细胞损伤在我们的研究中，子宫内多溴二苯醚暴露与人的相关性可能较低。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号