| Stability of arsenic metabolites, arsenic triglutathione [As(GS)3] and methylarsenic diglutathione [CH3As(GS)2], in rat bile. | |
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MedLine Citation:
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PMID: 15863254 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Inorganic arsenicals such as arsenite (iAs(III)) and arsenate (iAs(V)) are well-known human carcinogens. Arsenic is metabolized by repetitive reduction and oxidative methylation, and is excreted mainly in urine as monomethylated arsenicals (MMAs) and dimethylated arsenicals (DMAs). Recently, it has been shown that iAs(III) administered intravenously or orally is excreted into bile as arsenic-glutathione (As-GSH) complexes such as arsenic triglutathione [As(GS)(3)] and methylarsenic diglutathione [CH(3)As(GS)(2)]. In order to carry out the speciation of As-GSH complexes, it is important to understand their stability. The present study was designed to clarify the stability of As-GSH complexes in rat bile, and the role of GSH in stabilizing these complexes. Arsenic species were separated on an anion-exchange column and were analyzed by high-performance liquid chromatography-inductively coupled argon plasma mass spectrometry (HPLC-ICP MS). As(GS)(3) and CH(3)As(GS)(2) were unstable in bile and were hydrolyzed to iAs(III) and monomethylarsonous acid (MMA(III)) in the absence of GSH. As(GS)(3) appeared to be stable in the presence of 10mM GSH. Exogenously added GSH also stabilized CH(3)As(GS)(2) in bile at the concentrations of 5mM or higher. It has been suggested that trivalent arsenicals, especially MMA(III), are more toxic than corresponding pentavalent ones. These results suggest that GSH plays an important role in preventing hydrolysis of As-GSH complexes and the generation of well-known toxic trivalent arsenicals. |
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Authors:
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Yayoi Kobayashi; Xing Cui; Seishiro Hirano |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Toxicology Volume: 211 ISSN: 0300-483X ISO Abbreviation: Toxicology Publication Date: 2005 Jul |
Date Detail:
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Created Date: 2005-05-02 Completed Date: 2005-06-20 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0361055 Medline TA: Toxicology Country: Ireland |
Other Details:
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Languages: eng Pagination: 115-23 Citation Subset: IM |
Affiliation:
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Environmental Health Sciences Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506, Japan. kobayashi.yayoi@nies.go.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arsenic / metabolism*, pharmacokinetics Bile / metabolism* Chromatography, High Pressure Liquid Chromatography, Ion Exchange Glutathione / analogs & derivatives*, metabolism, pharmacokinetics Half-Life Injections, Intravenous Male Mass Spectrometry Rats Rats, Sprague-Dawley Reproducibility of Results |
| Chemical | |
Reg. No./Substance:
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70-18-8/Glutathione; 7440-38-2/Arsenic |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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