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无机砷及其甲基化代谢产物的组织特异性分布,尤其是在小鼠单次口服亚砷酸盐后在大脑皮层、小脑和海马体中的分布。

Tissue-specific distributions of inorganic arsenic and its methylated metabolites, especially in cerebral cortex, cerebellum and hippocampus of mice after a single oral administration of arsenite.

作者信息

Li Jinlong, Duan Xiaoxu, Dong Dandan, Zhang Yang, Zhao Lu, Li Wei, Chen Jinli, Sun Guifan, Li Bing

机构信息

Department of Occupational and Environmental Health, Key Laboratory of Arsenic-related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, Shenyang, 110013, China.

Department of Toxicology, School of Public Health, Shenyang Medical College, Shenyang, 110034, Liaoning, China.

出版信息

J Trace Elem Med Biol. 2017 Sep;43:15-22. doi: 10.1016/j.jtemb.2016.10.002. Epub 2016 Oct 4.

DOI:10.1016/j.jtemb.2016.10.002
PMID:27745987
Abstract

Groundwater contaminated with inorganic arsenic (iAs) is the main source of human exposure to arsenic and generates a global health issue. In this study, the urinary excretion, as well as the time-course distributions of various arsenic species in murine tissues, especially in different brain regions were determined after a single oral administration of 2.5, 5, 10 and 20mg/kg sodium arsenite (NaAsO). Our data showed that the peak times of urinary, hepatic and nephritic total arsenic (TAs) were happened at about 1h, then TAs levels decreased gradually and almost could not be observed after 72h. On contrast, the time course of TAs in lung, urinary bladder and different brain regions exhibited an obvious process of accumulation and elimination,and the peak times were nearly at 6h to 9h. TAs levels of 10 and 20mg/kg NaAsO groups were significantly higher than 2.5 and 5mg/kg groups, and the amounts of TAs in 5mg/kg groups were in the order of liver>lung>kidney>urinary bladder>hippocampus>cerebral cortex>cerebellum. In addition, iAs was the most abundant species in liver and kidney, while lung and urinary bladder accumulated the highest concentrations of dimethylated arsenicals (DMA). What's more, the distributions of arsenic species were not homogeneous among different brain regions, as DMA was the sole species in cerebral cortex and cerebellum, while extremely high concentrations and percentages of monomethylated arsenicals (MMA) were found in hippocampus. These results demonstrated that distributions of iAs and its methylated metabolites were tissue-specific and even not homogeneous among different brain regions, which must be considered as to the tissue- and region-specific toxicity of iAs exposure. Our results thus provide useful information for clarifying and reducing the uncertainty in the risk assessment for this metalloid.

摘要

受无机砷(iAs)污染的地下水是人类接触砷的主要来源,并引发了全球性的健康问题。在本研究中,单次口服2.5、5、10和20mg/kg亚砷酸钠(NaAsO)后,测定了小鼠组织中各种砷物种的尿排泄以及时间进程分布,特别是在不同脑区中的分布。我们的数据显示,尿、肝和肾总砷(TAs)的峰值时间约在1小时出现,然后TAs水平逐渐下降,72小时后几乎无法检测到。相比之下,肺、膀胱和不同脑区中TAs的时间进程呈现出明显的积累和消除过程,峰值时间接近6至9小时。10和20mg/kg NaAsO组的TAs水平显著高于2.5和5mg/kg组,5mg/kg组中TAs的含量顺序为肝脏>肺>肾脏>膀胱>海马体>大脑皮层>小脑。此外,iAs是肝脏和肾脏中含量最丰富的物种,而肺和膀胱中积累了最高浓度的二甲基化砷(DMA)。更重要的是,不同脑区中砷物种的分布并不均匀,因为DMA是大脑皮层和小脑中唯一的物种,而在海马体中发现了极高浓度和百分比的一甲基化砷(MMA)。这些结果表明,iAs及其甲基化代谢产物的分布具有组织特异性,甚至在不同脑区中也不均匀,在考虑iAs暴露的组织和区域特异性毒性时必须予以考虑。因此,我们的结果为澄清和降低这种类金属风险评估中的不确定性提供了有用信息。

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