The presence of arsenic-containing carbohydrates, arsenosugars, in many seafoods raises questions of human health concerning the ingestion and metabolism of these compounds. A previous study investigating the metabolites in human urine after the ingestion of a common arsenosugar 2',3'-dihydroxypropyl 5-deoxy-5-dimethylarsinoyl-beta-d-riboside (oxo-arsenosugar) showed that the arsenic was rapidly excreted in the urine and was present as at least 12 metabolites, only three of which could be identified. In this repeat study with oxo-arsenosugar and using high-performance liquid chromatography/inductively coupled plasma mass spectrometry, we report the identification of seven arsenic metabolites, which together accounted for 88% of the total urinary arsenic collected over 61 h. The metabolites included previously reported human urinary arsenicals dimethylarsinate (DMA), oxo-dimethylarsenoethanol (oxo-DMAE), and trimethylarsine oxide, in addition to new human metabolites oxo-dimethylarsenoacetate (oxo-DMAA), thio-dimethlyarsenoacetate (thio-DMAA), thio-dimethylarsenoethanol (thio-DMAE), and the thio-arsenosugar. Cytotoxicity testing of the major metabolites DMA, oxo-DMAE, thio-DMAE, oxo-DMAA, and thio-DMAA showed that they were nontoxic even at 10 mM, except for DMA, which showed some toxic effects at 1 mM.
To obtain quantitative information on human metabolism of selenium, we have performed selenium speciation analysis by HPLC/ICPMS on samples of human urine from one volunteer over a 48-hour period after ingestion of selenium (1.0 mg) as sodium selenite, L-selenomethionine, or DL-selenomethionine. The three separate experiments were performed in duplicate. Normal background urine from the volunteer contained total selenium concentrations of 8-30 microg Se/L (n=22) but, depending on the chromatographic conditions, only about 30-70% could be quantified by HPLC/ICPMS. The major species in background urine were two selenosugars, namely methyl-2-acetamido-2-deoxy-1-seleno-beta-D-galactopyranoside (selenosugar 1) and its deacylated analog methyl-2-amino-2-deoxy-1-seleno-beta-D-galactopyranoside (selenosugar 3). Selenium was rapidly excreted after ingestion of the selenium compounds: the peak concentrations (approximately 250-400 microg Se/L, normalized concentrations) were recorded within 5-9 hours, and concentrations had returned to close to background levels within 48 hours, by which time 25-40% of the ingested selenium, depending on the species ingested, had been accounted for in the urine. In all experiments, the major metabolite was selenosugar 1, constituting either approximately 80% of the total selenium excreted over the first 24 hours after ingestion of selenite or L-selenomethionine or approximately 65% after ingestion of DL-selenomethionine. Selenite was not present at significant levels (<1 microg Se/L) in any of the samples; selenomethionine was present in only trace amounts (approximately 1 microg/L, equivalent to less than 0.5% of the total Se) following ingestion of L-selenomethionine, but it constituted about 20% of the excreted selenium (first 24 hours) after ingestion of DL-selenomethionine, presumably because the D form was not efficiently metabolized. Trimethylselenonium ion, a commonly reported urine metabolite, could not be detected (<1 microg/L) in the urine samples after ingestion of selenite or selenomethionine. Cytotoxicity studies on selenosugar 1 and its glucosamine isomer (selenosugar 2, methyl-2-acetamido-2-deoxy-1-seleno-beta-D-glucosopyranoside) were performed with HepG2 cells derived from human hepatocarcinoma, and these showed that both compounds had low toxicity (about 1000-fold less toxic than sodium selenite). The results support earlier studies showing that selenosugar 1 is the major urinary metabolite after increased selenium intake, and they suggest that previously accepted pathways for human metabolism of selenium involving trimethylselenonium ion as the excretionary end product may need to be re-evaluated.
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