Vahter M, Couch R, Nermell B, Nilsson R
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Toxicol Appl Pharmacol. 1995 Aug;133(2):262-8. doi: 10.1006/taap.1995.1150.
Most mammals methylate inorganic arsenic (As) to methylarsonic acid (MMA) and dimethylarsinic acid, which are rapidly excreted in the urine. Previous studies have shown that, in contrast to humans, all experimental animals excrete very little MMA. With the aim of finding an appropriate animal model for studies on inorganic As metabolism and toxicity, we have investigated the metabolism of As in two male chimpanzees after a single iv dose of [73As]arsenate (5.8 micrograms As/kg body wt). The initial clearance from plasma was rapid with an apparent half-time of about 1 hr. Urine was found to constitute the major excretory pathway with very little excretion in the feces. About 60% of the administered 73As dose was excreted in the urine within 96 hr in a biphasic manner. The second phase of slow urinary excretion was characterized by first-order kinetics with a half-time of about 7 days. Upon ion-exchange chromatography of ultrafiltrated plasma and urine, only inorganic As could be detected, a finding confirmed by thin-layer chromatography. Thus, the results indicate that the chimpanzee, as previously shown for the marmoset monkey, but unlike all other mammals studied so far, including humans, is unable to methylate and detoxify inorganic As.
大多数哺乳动物会将无机砷（As）甲基化为甲基胂酸（MMA）和二甲基胂酸，这些物质会迅速通过尿液排出。先前的研究表明，与人类不同，所有实验动物排出的MMA都很少。为了找到一种适合研究无机砷代谢和毒性的动物模型，我们在两只雄性黑猩猩静脉注射单次剂量的[73As]砷酸盐（5.8微克砷/千克体重）后，研究了砷的代谢情况。血浆中的初始清除速度很快，表观半衰期约为1小时。发现尿液是主要的排泄途径，粪便中的排泄量很少。在96小时内，约60%的给药73As剂量以双相方式从尿液中排出。尿液缓慢排泄的第二阶段具有一级动力学特征，半衰期约为7天。对超滤后的血浆和尿液进行离子交换色谱分析时，仅能检测到无机砷，薄层色谱分析也证实了这一发现。因此，结果表明，正如先前对狨猴的研究所示，但与迄今为止研究的所有其他哺乳动物（包括人类）不同，黑猩猩无法将无机砷甲基化并解毒。
