Tissue- and Region-Specific Accumulation of Arsenic Species, Especially in the Brain of Mice, After Long-term Arsenite Exposure in Drinking Water

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Arsenic is identified as a known carcinogen and ubiquitously exists in nature. It appears that accumulation of inorganic arsenic (iAs) and its methylated metabolites in various tissues is closely correlated with the long-term toxicity and carcinogenicity of this metalloid. In this study, various arsenic species in murine tissues, especially in the cerebral cortex, cerebellum, and hippocampus, were determined after long-term exposure to 25, 50, 100, and 200 mg/L sodium arsenite in drinking water for 1 and 12 months. Our data showed that the amount of total arsenic (TAs) increased in an obvious dose-dependent manner in various tissues, and TAs levels were in the order of urinary bladder > brain > lung > liver > kidney > spleen. Furthermore, iAsIII and DMA could be observed in all tissues and brain regions with DMA being the predominant metabolite. The bladder, brain, and lung orderly contained the higher levels of DMA, while the liver, kidney, and spleen accumulated the higher proportion of iAsIII. MMA was preferentially accumulated in the lung and bladder of mice regardless of arsenic exposure doses or duration. What’s more, amazingly higher levels of MMA were observed in the hippocampus, which was distinguished from the cerebral cortex and cerebellum. Together with these results, our study clearly demonstrates that the accumulation of iAs and its methylated metabolites is tissue-specific and even not homogeneous among different brain regions in mice by long-term exposure to arsenite. Our study thus provides crucial information for recognizing arsenical neurotoxicity, and reducing the uncertainty in the risk assessment for this toxic metalloid.

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Fig. 1
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Fig. 3



Central nervous system


Inorganic arsenic

iAsV :

Pentavalent inorganic arsenic

iAsIII :

Trivalent inorganic arsenic


Monomethylarsonic acid


Monomethylarsonous acid


Dimethylarsinic acid


Dimethylarsinous acid


Monomethylated acid


Dimethylated acid


Total arsenic

NaAsO2 :

Sodium arsenite


Blood-brain barrier


Potassium hydroxide

H2SO4 :

Ultrapure sulfuric acid

(NH4)2HPO4 :

Diammonium phosphate


Limit of detection


One-way analysis of variation


Least significant difference


Arsenite methyltransferase


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Correspondence to Bing Li.

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All trials were approved by the Animal Care and Use Committee of China Medical University.

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Li, J., Guo, Y., Duan, X. et al. Tissue- and Region-Specific Accumulation of Arsenic Species, Especially in the Brain of Mice, After Long-term Arsenite Exposure in Drinking Water. Biol Trace Elem Res (2020) doi:10.1007/s12011-020-02033-x

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  • Inorganic arsenic
  • Arsenic species
  • Accumulation
  • Tissue-specific
  • Brain regions