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

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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 Jinlong Li 1,2 & Yuanyuan Guo 1 & Xiaoxu Duan 3 & Bing Li 1 Received: 16 October 2019 / Accepted: 1 January 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020

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 tissuespecific 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. Keywords Inorganic arsenic . Arsenic species . Accumulation . Tissue-specific . Brain regions

Abbreviations CNS Central nervous system iAs Inorganic arsenic

Jinlong Li and Yuanyuan Guo contributed equally to this work. * Bing Li [email protected] 1

Environment and Non-Communicable Disease Research Center, Key Laboratory of Arsenic-related Biological Effects and Prevention and Treatment in Liaoning Province, School of Public Health, China Medical University, No.77 Pu he Road, Shenyang North New Area, Shenyang, Liaoning Province 110122, People’s Republic of China

2

Department of Occupational and Environmental Health, Key Laboratory of Occupational Health and Safety for Coal Industry in Hebei Province, School of Public Health, North China University of Science and Technology, Tangshan 063210, China

3

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

iAsV iAsIII MMAV MMAIII DMAV DMAIII MMA DMA TAs NaAsO2 BBB KOH H2SO4 (NH4)2HPO4 LOD ANOVA LSD AS3MT

Pentavalent inorganic arsenic Trivalent inor