A novel metabolic activation associated with glutathione in dimethylmonothioarsinic acid (DMMTAV)-induced toxicity obtained from in vitro reaction of DMMTAV with glutathione

Kinetics of Dimethylated Thioarsenicals and the Formation of Highly Toxic Dimethylmonothioarsinic Acid in Environment

“…In urine collected from women exposed to As, dimethylated thioarsenicals accounted for up to 44% of the total As excreted, and a maximum concentration of 24 μg/L was observed . Recent research has focused on the metabolic pathways of dimethylated arsenicals both in vivo and in vitro, with special interest paid to highly toxic species such as glutathione conjugates. , …”

“…These dimethylated thioarsenicals are the products of thiolation of DMA V by H 2 S, with short reaction time (1 h) for DMMTA V but longer (up to 24 h) for DMDTA V . , The source of H 2 S is different according to the research groups: some use a gas cylinder of H 2 S, while others generate H 2 S by adding hydrochloric acid to iron sulfide or sulfuric acid to sodium sulfide solutions . There are several in vitro studies reporting DMMTA V formation from DMA III , not directly from DMA V . ,,, Recently, both DMA III and DMMTA V were also found to be possibly reconverted into DMA V during metabolic processes . Because DMA III reduced from DMA V is very unstable and rapidly converted to five-valent forms such as DMMTA V , DMA V is believed to be responsible for the formation of highly toxic DMMTA V in physiological condition. , …”

“…There are several in vitro studies reporting DMMTA V formation from DMA III , not directly from DMA V . ,,, Recently, both DMA III and DMMTA V were also found to be possibly reconverted into DMA V during metabolic processes . Because DMA III reduced from DMA V is very unstable and rapidly converted to five-valent forms such as DMMTA V , DMA V is believed to be responsible for the formation of highly toxic DMMTA V in physiological condition. , …”

“…7 Recent research has focused on the metabolic pathways of dimethylated arsenicals both in vivo and in vitro, with special interest paid to highly toxic species such as glutathione conjugates. 3,8 In terms of environmental implications, inorganic As species are of great concern due to their abundance. 9 The presence of thioarsenates, thiolated analogues of inorganic As species, has been reported in groundwater, 10 geothermal water, 11−13 and leachate, 14 and the mechanism of the formation or transformation of thioarsenates in sulfidic or iron-rich sulfidic conditions has been studied by several research groups.…”

“…3 Because DMA III reduced from DMA V is very unstable and rapidly converted to fivevalent forms such as DMMTA V , DMA V is believed to be responsible for the formation of highly toxic DMMTA V in physiological condition. 4,8 Conklin and colleagues 24 have reported that the conversion of monomethylarsonic acid (MMA V ), DMA V , and trimethylarsine oxide (TMAO) to their thiolated forms is pHdependent and has been observed in laboratory tests in the presence of sulfide at pH ≤ 7. Monothiolated forms are the primary species at pH 3, whereas >92% of initial DMA V is converted to DMDTA V and to a lesser extent DMMTA V at pH 5−7 after 46 h. 24 The microbial formation of DMDTA V , DMMTA V , and monomethyldithioarsonic acid (MMDTA V ) has been observed over a period of 43 days in municipal landfill leachate using an As spiking test.…”