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

详细信息    查看全文

• 作者：Hidetoshi Kurosawa^a ; ^b ; Yasuyo Shimoda^a ; Motofumi Miura^c ; Koichi Kato^a ; Kenzo Yamanaka^a ; ^{yamanaka.kenzo@nihon-u.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Akihisa Hata^d ; Yuko Yamano^e ; Yoko Endo^f ; Ginji Endo^g
• 关键词：Dimethylmonothioarsinic acid ; Dimethylarsinic acid ; Dimethylarsinous acid ; Dimethylmercaptoarsine
• 刊名：Journal of Trace Elements in Medicine and Biology
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：33
• 期：Complete
• 页码：87-94
• 全文大小：1619 K

文摘

The purpose of the present study was to elucidate the metabolic processing of dimethylmonothioarsinic acid (DMMTA^V), 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 (DMA^V) with GSH did not generate DMA^V-SG but did generate dimethylarsinous acid (DMA^III) or DMA^III-SG. On the contrary, we confirmed that the reaction of DMMTA^V with GSH directly produced the stable complex of DMMTA^V-SG without reduction through a trivalent dimethylated arsenic such as DMA^III and DMA^III-SG. Furthermore, the present study suggests the production of hydrogen sulfide (H₂S) and dimethylmercaptoarsine (DMA^III-SH), a trivalent dimethylated arsenic, as well as DMA^III and DMA^III-SG in the decomposition process of DMMTA^V-SG. These results indicate that the toxicity of DMMTA^V depends not only on the formation of DMA^III but also on at least those of H₂S and DMA^III-SH.