Arsenic Speciation in the Blood of Arsenite-Treated F344 Rats

• Published in: Chemical research in toxicology 2013-06, Vol.26 (6), p.952-962
• Main Authors: Chen, Baowei, Lu, Xiufen, Shen, Shengwen, Arnold, Lora L, Cohen, Samuel M, Le, X. Chris
• Format: Article
• Language: English
• Subjects: Animals; Arsenic - blood; Arsenic - chemistry; Arsenites - blood; Arsenites - pharmacology; Chromatography, High Pressure Liquid; Diet; Female; Rats; Rats, Inbred F344; Spectrometry, Mass, Electrospray Ionization
• ISSN: 0893-228X; 1520-5010
• DOI: 10.1021/tx400123q

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, DMAV was consistently found as the predominant arsenic species, probably reflecting the preferential binding of dimethylarsinous acid (DMAIII) 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.