Arsenic metabolism and thioarsenicals in hamsters and rats
Arsenic metabolism and thioarsenicals in hamsters and rats
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DOI：
10.1021/tx700038x
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发表时间：
2007-04-01
影响因子：
4.1
通讯作者：
Suzuki, Kazuo T.
中科院分区：
文献类型：
--
作者：
Naranmandura, Hua;Suzuki, Noriyuki;Suzuki, Kazuo T.
比较了砷在两种代谢能力和毒性不同的动物体内的组织分布和化学形态。以5.0 mg As/kg体重的剂量对仓鼠和大鼠单次口服亚砷酸盐（iAs（III）），测定砷的浓度;超过75%的剂量以二甲基亚胂酸（DMA（III））的形式在大鼠红细胞（RBC）中蓄积，而在仓鼠RBC中蓄积的剂量低于0.8%，主要以一甲基亚胂酸（MMA（III））的形式存在。一周内在仓鼠尿液中回收了超过63%的剂量（比大鼠尿液高7.8倍），反映了RBC中的低蓄积。砷在仓鼠肝脏和肾脏中的分布量显著高于大鼠，且砷在仓鼠肝脏中的停留时间远长于大鼠。砷积累更多，并保留在肾脏中的时间比在这两种动物的肝脏，在仓鼠肾脏，它积累的水平高于在大鼠肾脏中的MMA（III）结合蛋白质的形式。在前24小时的尿液中，在仓鼠中检测到二甲基一硫代砷酸（DMMTA（V））和二甲基二硫代砷酸（DMDTA（V）），但在大鼠中仅发现DMMTA（V），以及两种动物中未知的砷代谢物。未知的尿砷代谢物被鉴定为单甲基硫代胂酸（MMMTA（V）; CH 3As（S）（OH）（2））。本研究结果表明，在仓鼠，砷不会积累在红细胞，因此，仓鼠表现出更均匀的组织分布和更快的尿排泄的砷比大鼠。此外，砷的巯基化更多的仓鼠比大鼠排泄单和二甲基硫代砷在尿液中。
The tissue distribution and chemical forms of arsenic were compared in two animal species with different metabolic capacity and toxicity to arsenic. Hamsters and rats were given a single oral dose of arsenite (iAs(III)) at 5.0 mg As/kg body weight, and then the concentrations of arsenic were determined; more than 75% of the dose accumulated in rat red blood cells (RBCs) in the form of dimethylarsinous acid (DMA(III)), whereas less than 0.8% of the dose accumulated in hamster RBCs, mostly in the form of monomethylarsonous acid (MMA(III)). Reflecting the low accumulation in RBCs, more than 63% of the dose was recovered in hamster urine within one week (7.8-fold higher than that in rat urine). The quantity of arsenic distributed in the liver and kidneys was significantly higher in hamsters than in rats, and arsenic in livers stayed much longer in hamsters than in rats. Arsenic accumulated more and was retained longer in the kidneys than in the livers in both animals, and in hamster kidneys, it accumulated at levels higher than those in rat kidneys in the form of MMA(III) bound to proteins. In the first 24 h urine, dimethylmonothioarsinic (DMMTA(V)) and dimethyldithioarsinic (DMDTA(V)) acids were detected in hamsters, but only DMMTA(V) was found in rats, together with an unknown arsenic metabolite in both animals. The unknown urinary arsenic metabolite was identified as monomethylmonothioarsonic acid (MMMTA(V); CH3As(S)(OH)(2)). The present results indicate that in hamsters, arsenic does not accumulate in RBCs, and therefore, hamsters exhibit a more uniform tissue distribution and faster urinary excretion of arsenic than rats. In addition, arsenic was thiolated more in hamsters than in rats excreting mono and dimethylated thioarsenicals in urine.