Distribution and metabolism of four different dimethylated arsenicals in hamsters


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Abstract

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 (DMAV), dimethylarsinous acid (DMAIII), dimethylmonothioarsinic acid (DMMTAV), and dimethyldithioarsinic acid (DMDTAV) after the administration of them into femoral vein of hamsters. DMAV and DMDTAV distributed in organs and body fluids were in their unmodified form, while DMAIII and DMMTAV were bound to proteins and transformed to DMAV in organs. On the other hand, DMAV and DMDTAV 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 DMAV, while more than 60% of doses were distributed in muscles and target organs (liver, kidney, and lung) of hamsters after the injection of DMMTAV and DMAIII. 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 DMAIII and DMMTAV, suggesting that the DMAIII and DMMTAV were hardly accumulated in hamster RBCs. Based on these observations, we suggest that although DMMTAV and DMDTAV are thioarsenicals, DMMTAV is taken up efficiently by organs, in a manner different from that of DMDTAV. In addition, the distribution and metabolism of DMMTAV are like in manner similar to DMAIII in hamsters, while DMDTAV is in a manner similar to DMAV.

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