Urinary Sulfur-Containing Metabolite Produced by Intestinal Bacteria Following Oral Administration of Dimethylarsinic Acid to Rats
| Autor: | Koichi Kuroda, Ginji Endo, Shoji Fukushima, Yukiko Date, Hideki Wanibuchi, Yoshinori Inoue, Xu Zhou, Kaoru Yoshida |
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| Rok vydání: | 2003 |
| Předmět: |
Spectrometry
Mass Electrospray Ionization Metabolite Administration Oral Exotoxins chemistry.chemical_element HL-60 Cells Toxicology Arsenicals Superoxide dismutase chemistry.chemical_compound Cacodylic acid Escherichia coli Animals Cacodylic Acid Humans Cysteine Intestinal Mucosa Hydrogen peroxide Cytotoxicity Chromatography High Pressure Liquid Arsenic chemistry.chemical_classification Reactive oxygen species Chromatography Sulfur Compounds biology Superoxide Dismutase Hydrogen Peroxide General Medicine Rats Intestines chemistry Biochemistry biology.protein Female |
| Zdroj: | Chemical Research in Toxicology. 16:1124-1129 |
| ISSN: | 1520-5010 0893-228X |
| DOI: | 10.1021/tx030008x |
| Popis: | Our long-term oral administration of dimethylarsinic acid (DMAV) in rats revealed that three unidentified metabolites, M-1, M-2, and M-3, were detected in urine and feces. DMAV and trimethylarsine oxide (TMAO) were converted to M-2 and M-3 and M-1 by Escherichia coli strain A3-6 isolated from the ceca of DMAV-administered rats, respectively. In this study, we report on the mechanism of production and the chemical properties of these unknown metabolites. To investigate the pattern of conversion of DMAV or TMAO by A3-6 in the presence of cysteine (Cys), arsenic metabolites of DMAV or TMAO in medium after incubation with A3-6 and Cys were analyzed by liquid chromatography with inductively coupled plasma mass spectrometry (LC-ICP-MS). DMAV was reduced to dimethylarsinous acid (DMAIII) to form M-2 in the presence of Cys and A3-6, and M-2 was further converted to M-3. TMAO was rapidly converted to M-1 by A3-6. The cytotoxicity of the unidentified metabolites was investigated. M-2 was more cytotoxic than DMAV, M-1, and M-3 in V79 cells. The cytotoxicity of M-2 in HL-60 cells was decreased by the addition of superoxide dismutase, suggesting that the cytotoxicity of M-2 might be due to the production of reactive oxygen species. In addition, we examined the chemical properties of M-2 by LC-ICP-MS and LC-MS. M-2 was oxidized to DMAV by hydrogen peroxide, suggesting that M-2 may be a reduced form of DMAV. M-2 was consistent with the reactant of DMAV with metabisulfite-thiosulfate reagent but not DMAIII by analyses of LC-ICP-MS and LC-MS. The molecular weight of M-2 was 154, and M-2 was a sulfur-containing metabolite. |
| Databáze: | OpenAIRE |
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