Identification of Methylated Dithioarsenicals in the Urine of Rats Fed with Sodium Arsenite

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

Research output: Contribution to journalArticle

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Abstract

Biotransformation of inorganic arsenic results in the formation of methylarsenicals of both oxygen and sulfur analogues. Aiming to improve our understanding of metabolism of inorganic arsenic in animals, we conducted an animal feeding study with an emphasis on identifying new arsenic metabolites. Female F344 rats were given 0, 1, 10, 25, 50, and 100 μg/g of arsenite (iAsIII) in the diet. Arsenic species in rat urine were determined using high performance liquid chromatography (HPLC) separation and inductive coupled plasma mass spectrometry (ICPMS) and electrospray ionization tandem mass spectrometry (ESI MS/MS) detection. Nine arsenic species were detected in the urine of the iAsIII-dosed rats. Seven of these arsenic species were consistent with previous reports, including iAsIII, arsenate, monomethyarsonic acid, dimethylarsinic acid, trimethylarsine oxide, monomethylmonothioarsonic acid, and dimethylmonothioarsinic acid. Two new methyldithioarsencals, monomethyldithioarsonic acid (MMDTAV) and dimethyldithioarsinic acid (DMDTAV), were identified for the first time in the urine of rats treated with iAsIII. The concentrations of both MMDTAV and DMDTAV in rat urine were dependent on the dosage of iAsIII in diet. The concentration of DMDTAV was approximately 5 times higher than that of MMDTAV. MMDTAV has not been identified in any biological samples of animals, and DMDTAV has not been reported as a metabolite of inorganic arsenic in the rats. The identification of novel methylated dithioarsenicals as metabolites of inorganic arsenic in the rat urine provided further insights into the understanding of the metabolism of arsenic.

Original languageEnglish (US)
Pages (from-to)1480-1487
Number of pages8
JournalChemical Research in Toxicology
Volume29
Issue number9
DOIs
StatePublished - Sep 19 2016

Fingerprint

Arsenic
Rats
Urine
Metabolites
Animals
Nutrition
Metabolism
Mass spectrometry
Cacodylic Acid
Diet
sodium arsenite
Electrospray ionization
Acids
Electrospray Ionization Mass Spectrometry
Inbred F344 Rats
High performance liquid chromatography
Biotransformation
Tandem Mass Spectrometry
Sulfur
Mass Spectrometry

ASJC Scopus subject areas

  • Toxicology

Cite this

Identification of Methylated Dithioarsenicals in the Urine of Rats Fed with Sodium Arsenite. / Chen, Baowei; Lu, Xiufen; Arnold, Lora L; Cohen, Samuel Monroe; Le, X. Chris.

In: Chemical Research in Toxicology, Vol. 29, No. 9, 19.09.2016, p. 1480-1487.

Research output: Contribution to journalArticle

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abstract = "Biotransformation of inorganic arsenic results in the formation of methylarsenicals of both oxygen and sulfur analogues. Aiming to improve our understanding of metabolism of inorganic arsenic in animals, we conducted an animal feeding study with an emphasis on identifying new arsenic metabolites. Female F344 rats were given 0, 1, 10, 25, 50, and 100 μg/g of arsenite (iAsIII) in the diet. Arsenic species in rat urine were determined using high performance liquid chromatography (HPLC) separation and inductive coupled plasma mass spectrometry (ICPMS) and electrospray ionization tandem mass spectrometry (ESI MS/MS) detection. Nine arsenic species were detected in the urine of the iAsIII-dosed rats. Seven of these arsenic species were consistent with previous reports, including iAsIII, arsenate, monomethyarsonic acid, dimethylarsinic acid, trimethylarsine oxide, monomethylmonothioarsonic acid, and dimethylmonothioarsinic acid. Two new methyldithioarsencals, monomethyldithioarsonic acid (MMDTAV) and dimethyldithioarsinic acid (DMDTAV), were identified for the first time in the urine of rats treated with iAsIII. The concentrations of both MMDTAV and DMDTAV in rat urine were dependent on the dosage of iAsIII in diet. The concentration of DMDTAV was approximately 5 times higher than that of MMDTAV. MMDTAV has not been identified in any biological samples of animals, and DMDTAV has not been reported as a metabolite of inorganic arsenic in the rats. The identification of novel methylated dithioarsenicals as metabolites of inorganic arsenic in the rat urine provided further insights into the understanding of the metabolism of arsenic.",
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