仓鼠和大鼠体内的砷代谢与硫代砷化合物

Arsenic metabolism and thioarsenicals in hamsters and rats.

作者信息

Naranmandura Hua, Suzuki Noriyuki, Iwata Katsuya, Hirano Seishiro, Suzuki Kazuo T

机构信息

Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.

出版信息

Chem Res Toxicol. 2007 Apr;20(4):616-24. doi: 10.1021/tx700038x. Epub 2007 Mar 24.

Abstract

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 (iAsIII) 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 (DMAIII), whereas less than 0.8% of the dose accumulated in hamster RBCs, mostly in the form of monomethylarsonous acid (MMAIII). 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 MMAIII bound to proteins. In the first 24 h urine, dimethylmonothioarsinic (DMMTAV) and dimethyldithioarsinic (DMDTAV) acids were detected in hamsters, but only DMMTAV was found in rats, together with an unknown arsenic metabolite in both animals. The unknown urinary arsenic metabolite was identified as monomethylmonothioarsonic acid (MMMTAV; 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.

摘要

在对砷具有不同代谢能力和毒性的两种动物物种中比较了砷的组织分布和化学形态。给仓鼠和大鼠经口单次给予5.0 mg砷/千克体重的亚砷酸盐(iAsIII),然后测定砷的浓度;超过75%的剂量以二甲基亚胂酸(DMAIII)的形式积累在大鼠红细胞(RBC)中,而在仓鼠红细胞中积累的剂量不到0.8%,主要以一甲基亚胂酸(MMAIII)的形式存在。由于在红细胞中的积累较低,超过63%的剂量在一周内从仓鼠尿液中回收(比大鼠尿液高7.8倍)。仓鼠肝脏和肾脏中分布的砷量明显高于大鼠,并且仓鼠肝脏中的砷停留时间比大鼠长得多。在两种动物中,砷在肾脏中的积累比在肝脏中更多且保留时间更长,在仓鼠肾脏中,它以与蛋白质结合的MMAIII形式积累的水平高于大鼠肾脏。在最初24小时的尿液中,在仓鼠中检测到二甲基单硫代胂酸(DMMTAV)和二甲基二硫代胂酸(DMDTAV),但在大鼠中仅发现了DMMTAV,两种动物中还存在一种未知的砷代谢物。未知的尿砷代谢物被鉴定为一甲基单硫代胂酸(MMMTAV;CH3As(=S)(OH)2)。目前的结果表明,在仓鼠中,砷不会在红细胞中积累,因此,仓鼠比大鼠表现出更均匀的组织分布和更快的尿砷排泄。此外,与大鼠相比,仓鼠中砷的硫醇化程度更高,在尿液中排泄单甲基和二甲基硫代砷化合物。

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