Institute of Pharmacology & Toxicology and Biochemical Pharmaceutics, Zhejiang University, Hangzhou 310058, China.
Toxicol Appl Pharmacol. 2010 May 15;245(1):67-75. doi: 10.1016/j.taap.2010.02.001. Epub 2010 Feb 6.
Arsenic toxicity and distribution are highly dependent on animal species and its chemical species. Recently, thioarsenical has been recognized in highly toxic arsenic metabolites, which was commonly found in human and animal urine. In the present study, we revealed the mechanism underlying the distribution and metabolism of non-thiolated and thiolated dimethylarsenic compounds such as dimethylarsinic acid (DMA(V)), dimethylarsinous acid (DMA(III)), dimethylmonothioarsinic acid (DMMTA(V)), and dimethyldithioarsinic acid (DMDTA(V)) after the administration of them into femoral vein of hamsters. DMA(V) and DMDTA(V) distributed in organs and body fluids were in their unmodified form, while DMA(III) and DMMTA(V) were bound to proteins and transformed to DMA(V) in organs. On the other hand, DMA(V) and DMDTA(V) were mostly excreted into urine as their intact form 1 h after post-injection, and more than 70% of the doses were recovered in urine as their intact form. By contrast, less than 8-14% of doses were recovered in urine as DMA(V), while more than 60% of doses were distributed in muscles and target organs (liver, kidney, and lung) of hamsters after the injection of DMMTA(V) and DMA(III). However, in red blood cells (RBCs), only a small amount of the arsenicals was distributed (less than 4% of the doses) after the injection of DMA(III) and DMMTA(V), suggesting that the DMA(III) and DMMTA(V) were hardly accumulated in hamster RBCs. Based on these observations, we suggest that although DMMTA(V) and DMDTA(V) are thioarsenicals, DMMTA(V) is taken up efficiently by organs, in a manner different from that of DMDTA(V). In addition, the distribution and metabolism of DMMTA(V) are like in manner similar to DMA(III) in hamsters, while DMDTA(V) is in a manner similar to DMA(V).
砷的毒性和分布高度依赖于动物物种及其化学形态。最近，硫代砷被认为是高毒性砷代谢物的一种，常见于人和动物的尿液中。在本研究中，我们揭示了非硫代和硫代二甲基砷化合物（如二甲基砷酸（DMA(V)）、二甲基亚砷酸（DMA(III)）、二甲基单硫代砷酸（DMMTA(V)）和二甲基二硫代砷酸（DMDTA(V)））在进入仓鼠股静脉后分布和代谢的机制。DMA(V)和 DMDTA(V)在器官和体液中的分布形式保持不变，而 DMA(III)和 DMMTA(V)则与蛋白质结合，并在器官中转化为 DMA(V)。另一方面，DMA(V)和 DMDTA(V)在注射后 1 小时内主要以其完整形式从尿液中排出，超过 70%的剂量以其完整形式从尿液中回收。相比之下，DMMTA(V)和 DMA(III)注射后，不到 8-14%的剂量以 DMA(V)的形式从尿液中回收，而超过 60%的剂量分布在肌肉和靶器官（肝、肾和肺）中。然而，在红细胞（RBCs）中，注射 DMA(III)和 DMMTA(V)后，只有少量的砷化物分布（不到剂量的 4%），表明 DMA(III)和 DMMTA(V)几乎不会在仓鼠 RBCs 中积累。基于这些观察结果，我们认为，尽管 DMMTA(V)和 DMDTA(V)是硫代砷，但 DMMTA(V)被器官有效摄取，其方式不同于 DMDTA(V)。此外，DMMTA(V)在仓鼠中的分布和代谢方式类似于 DMA(III)，而 DMDTA(V)则类似于 DMA(V)。
