Kimpe J D, Cornelis R, Mees L, Vanholder R
Laboratory for Analytical Chemistry, Institute for Nuclear Sciences, University of Gent, Proeftuinstraat 86, Gent, B-9000, Belgium.
Fundam Appl Toxicol. 1996 Dec;34(2):240-8. doi: 10.1006/faat.1996.0193.
The time-dependent occurrence of [74As]arsenate metabolites in Flemish Giant rabbits was investigated. As absorbed rapidly, reaching maximal concentrations in plasma and packed cells after 30 min and 2 hr, respectively. The [74As]arsenate in plasma and packed cells was reduced to [74As]arsenite, to 35 and 50% of the total 74As, respectively. The concentration of methylated As species in plasma and packed cells increased rapidly after 30 min. About 18% of total plasma 74As maximally bound to transferrin. Two-thirds of total 74As in packed cells bound to hemoglobin. Whereas little or no [74As]monomethylarsonic acid, one of the main As metabolites in humans, could be found in other animals, it is present in measurable amounts in the Flemish Giant. Furthermore, the plasma clearance rate of 74As species is lower than that in other rabbits and more similar to that of humans. The tissue 74As distribution varied widely with the highest concentrations in kidneys, liver, and lungs. 74As accumulated in bone whereas other tissues and blood showed rapid clearance rates. In muscle and heart an important part of arsenic was associated with components insoluble in phosphate-buffered isotonic saline. Binding of arsenic to soluble tissue proteins was most important in the kidneys, liver, and spleen. [74As]Arsenate metabolites were detected in all tissues. The relative amounts of [74As]arsenite or [74As]monomethylarsonic acid seldom exceeded 15% of total tissue 74As. The proportion of [74As]dimethylarsenic acid in the low molecular 74As fraction increased steadily. Substantial amounts of [74As]monomethylarsonic acid were found in the tissues..
研究了弗拉芒巨兔体内[74As]砷酸盐代谢物随时间的出现情况。砷吸收迅速,分别在30分钟和2小时后在血浆和红细胞中达到最大浓度。血浆和红细胞中的[74As]砷酸盐分别还原为[74As]亚砷酸盐,占总74As的35%和50%。30分钟后,血浆和红细胞中甲基化砷物种的浓度迅速增加。血浆中总74As的约18%最大程度地与转铁蛋白结合。红细胞中总74As的三分之二与血红蛋白结合。虽然在其他动物中很少或几乎找不到人类主要砷代谢物之一的[74As]一甲基砷酸,但在弗拉芒巨兔中其含量可测。此外,74As物种的血浆清除率低于其他兔子,更接近人类。组织中74As的分布差异很大,肾脏、肝脏和肺部浓度最高。74As在骨骼中蓄积,而其他组织和血液的清除率很快。在肌肉和心脏中,砷的重要部分与磷酸盐缓冲等渗盐水中不溶性成分相关。砷与可溶性组织蛋白的结合在肾脏、肝脏和脾脏中最为重要。在所有组织中都检测到了[74As]砷酸盐代谢物。[74As]亚砷酸盐或[74As]一甲基砷酸的相对含量很少超过组织总74As的15%。低分子74As组分中[74As]二甲基砷酸的比例稳步增加。在组织中发现了大量的[74As]一甲基砷酸。