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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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Abstract

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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Abbreviations

CNS:

Central nervous system

iAs:

Inorganic arsenic

iAsV :

Pentavalent inorganic arsenic

iAsIII :

Trivalent inorganic arsenic

MMAV :

Monomethylarsonic acid

MMAIII :

Monomethylarsonous acid

DMAV :

Dimethylarsinic acid

DMAIII :

Dimethylarsinous acid

MMA:

Monomethylated acid

DMA:

Dimethylated acid

TAs:

Total arsenic

NaAsO2 :

Sodium arsenite

BBB:

Blood-brain barrier

KOH:

Potassium hydroxide

H2SO4 :

Ultrapure sulfuric acid

(NH4)2HPO4 :

Diammonium phosphate

LOD:

Limit of detection

ANOVA:

One-way analysis of variation

LSD:

Least significant difference

AS3MT:

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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Keywords

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