Distribution and metabolism of four different dimethylated arsenicals in hamsters.
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).
Institute of Pharmacology & Toxicology and Biochemical Pharmaceutics, Zhejiang University, Hangzhou 310058, China. narenman@zju.edu.cn
Hua
H
Naranmandura
Katsuya
K
Iwata
Kazuo T
KT
Suzuki
Yasumitsu
Y
Ogra
D000818:Animals; D002101:Cacodylic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006224:Cricetinae; D004912:Erythrocytes / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D012867:Skin / Q000378:metabolism; D001149:Arsenates
D002101:Cacodylic Acid; C472511:dimethylarsinous acid; C518668:dimethyldithioarsinic acid; C518667:dimethylmonothioarsinic acid; D001149:Arsenates