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

作者: Hidetoshi Kurosawa , Yasuyo Shimoda , Motofumi Miura , Koichi Kato , Kenzo Yamanaka

DOI: 10.1016/J.JTEMB.2015.10.002

关键词: MetaboliteGas chromatographyHigh-performance liquid chromatographyNuclear chemistryChemistryToxicityArsenicInorganic chemistryMass spectrometryGlutathioneCacodylic acidMolecular medicineBiochemistry

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

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