Arsenic speciation in the blood of arsenite-treated F344 rats

Baowei Chen, Xiufen Lu, Shengwen Shen, Lora L Arnold, Samuel Monroe Cohen, X. Chris Le

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Arsenic speciation in blood can improve understanding of the metabolism and toxicity of arsenic. In this study, arsenic species in the plasma and red blood cells (RBCs) of arsenite-treated female F344 rats were characterized using anion exchange and size exclusion chromatography separation with inductively coupled plasma mass spectrometry (ICPMS) and electrospray ionization tandem mass spectrometry (ESI MS/MS) detection. Arsenite (iAsIII), arsenate (iAsV), monomethylarsonic acid (MMAV), dimethylarsinic acid (DMAV), trimethylarsine oxide (TMAOV), monomethylmonothioarsonic acid (MMMTAV), and dimethylmonothioarsinic acid (DMMTAV) were detected in the plasma, with DMAV being the predominant metabolite. Upon oxidative pretreatment with 5% hydrogen peroxide (H2O2), plasma proteins released bound arsenic in the form of DMAV as the major species and MMAV as the minor species. The ratio of protein-bound arsenic to total arsenic decreased with increasing dosage of iAsIII administered to the rats, suggesting a possible saturation of the binding capacity of the plasma proteins. The proportion of the protein-bound arsenic in the plasma varied among rats. In the H2O2-treated lysates of red blood cells of rats, DMA V was consistently found as the predominant arsenic species, probably reflecting the preferential binding of dimethylarsinous acid (DMA III) to rat hemoglobin. iAsV, MMAV, and trimethylarsine oxide (TMAOV) were also detected in the hydrogen peroxide-treated lysates of red blood cells. Importantly, DMMTAV and MMMTAV have not been reported in rat blood, and the present finding of DMMTAV and MMMTAV in the rat plasma is toxicologically relevant because these pentavalent thioarsenicals are more toxic than their counterparts DMAV and MMAV. Identifying novel thiolated arsenicals and determining protein-bound arsenicals in the blood provide useful insights into the metabolism and toxicity of arsenic in animals.

Original languageEnglish (US)
Pages (from-to)952-962
Number of pages11
JournalChemical Research in Toxicology
Volume26
Issue number6
DOIs
StatePublished - Jun 17 2013

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Inbred F344 Rats
Arsenic
Rats
Blood
Arsenicals
Plasmas
Erythrocytes
Cells
Dynamic mechanical analysis
Metabolism
Hydrogen Peroxide
Toxicity
Blood Proteins
Cacodylic Acid
arsenite
Inductively coupled plasma mass spectrometry
Electrospray ionization
Proteins
Size exclusion chromatography
Electrospray Ionization Mass Spectrometry

ASJC Scopus subject areas

  • Toxicology

Cite this

Arsenic speciation in the blood of arsenite-treated F344 rats. / Chen, Baowei; Lu, Xiufen; Shen, Shengwen; Arnold, Lora L; Cohen, Samuel Monroe; Le, X. Chris.

In: Chemical Research in Toxicology, Vol. 26, No. 6, 17.06.2013, p. 952-962.

Research output: Contribution to journalArticle

Chen, Baowei ; Lu, Xiufen ; Shen, Shengwen ; Arnold, Lora L ; Cohen, Samuel Monroe ; Le, X. Chris. / Arsenic speciation in the blood of arsenite-treated F344 rats. In: Chemical Research in Toxicology. 2013 ; Vol. 26, No. 6. pp. 952-962.
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abstract = "Arsenic speciation in blood can improve understanding of the metabolism and toxicity of arsenic. In this study, arsenic species in the plasma and red blood cells (RBCs) of arsenite-treated female F344 rats were characterized using anion exchange and size exclusion chromatography separation with inductively coupled plasma mass spectrometry (ICPMS) and electrospray ionization tandem mass spectrometry (ESI MS/MS) detection. Arsenite (iAsIII), arsenate (iAsV), monomethylarsonic acid (MMAV), dimethylarsinic acid (DMAV), trimethylarsine oxide (TMAOV), monomethylmonothioarsonic acid (MMMTAV), and dimethylmonothioarsinic acid (DMMTAV) were detected in the plasma, with DMAV being the predominant metabolite. Upon oxidative pretreatment with 5{\%} hydrogen peroxide (H2O2), plasma proteins released bound arsenic in the form of DMAV as the major species and MMAV as the minor species. The ratio of protein-bound arsenic to total arsenic decreased with increasing dosage of iAsIII administered to the rats, suggesting a possible saturation of the binding capacity of the plasma proteins. The proportion of the protein-bound arsenic in the plasma varied among rats. In the H2O2-treated lysates of red blood cells of rats, DMA V was consistently found as the predominant arsenic species, probably reflecting the preferential binding of dimethylarsinous acid (DMA III) to rat hemoglobin. iAsV, MMAV, and trimethylarsine oxide (TMAOV) were also detected in the hydrogen peroxide-treated lysates of red blood cells. Importantly, DMMTAV and MMMTAV have not been reported in rat blood, and the present finding of DMMTAV and MMMTAV in the rat plasma is toxicologically relevant because these pentavalent thioarsenicals are more toxic than their counterparts DMAV and MMAV. Identifying novel thiolated arsenicals and determining protein-bound arsenicals in the blood provide useful insights into the metabolism and toxicity of arsenic in animals.",
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