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

The purpose of the present study was to elucidate the metabolic processing of dimethylmonothioarsinic acid (DMMTAV), which is a metabolite of inorganic arsenic and has received a great deal of attention recently due to its high toxicity. The metabolites produced from an in vitro reaction with GSH were analyzed by high performance liquid chromatography-time of flight mass spectrometer (HPLC-TOFMS), HPLC with a photodiode array detector (PDA), and also gas chromatography-mass spectrometry (GC-MS) and GC with a flame photometric detector (FPD). The reaction of dimethylarsinic acid (DMAV) with GSH did not generate DMAV-SG but did generate dimethylarsinous acid (DMAIII) or DMAIII-SG. On the contrary, we confirmed that the reaction of DMMTAV with GSH directly produced the stable complex of DMMTAV-SG without reduction through a trivalent dimethylated arsenic such as DMAIII and DMAIII-SG. Furthermore, the present study suggests the production of hydrogen sulfide (H2S) and dimethylmercaptoarsine (DMAIII-SH), a trivalent dimethylated arsenic, as well as DMAIII and DMAIII-SG in the decomposition process of DMMTAV-SG. These results indicate that the toxicity of DMMTAV depends not only on the formation of DMAIII but also on at least those of H2S and DMAIII-SH.