Metabolites of arsenobetaine in rats: does decomposition of arsenobetaine occur in mammals?

Abstract

AbstractBiotransformation following oral administration of arsenobetaine (AsBe), the major arsenic compound in marine animals, was studied in rats. Male F344/DuCrj rats were administered a single dose of AsBe (20 mg As kg−1) orally. Urine was collected at 0, 2, 4, 6, 8, 10, 12, 24, 48, 72, and 96 h after administration by forced urination. Arsenic metabolites in urine were analyzed by ion chromatography with inductively coupled plasma mass spectrometry. Urinary elimination of AsBe, trimethylarsine oxide (TMAO), dimethylarsinic acid (DMA), methylarsonic acid (MMA), tetramethylarsonium (TeMA), an unidentified arsenic metabolite, arsenate, and arsenite was determined at various time points after administration. Unmetabolized AsBe was the most common form. Most elimination of unchanged AsBe occurred within 48 h, with peak elimination between 0 and 2 h. A small portion of administered AsBe was eliminated as TMAO and TeMA, with peak elimination between 0 and 2 h. Elimination of the unidentified metabolite, MMA, DMA, and inorganic arsenic occurred later and to a slight extent. A delay in elimination of the unidentified compound, MMA, DMA, and inorganic arsenic compared with that of TMAO suggests that the former compounds may be formed from TMAO. Degradation of AsBe by an intestinal bacterium, Escherichia coli, did not occur in rats. These results suggest that TMAO may be formed from AsBe, and that TMAO may subsequently be converted to the unidentified compound and demethylated arsenic compounds. Copyright ­© 2001 John Wiley & Sons, Ltd.