Mitchell R D, Ayala-Fierro F, Carter D E
Department of Pharmacology and Toxicology, Center for Toxicology's Superfund Basic Research Program, College of Pharmacy, University of Arizona, Tucson 85721, USA.
J Toxicol Environ Health A. 2000 Jan 28;59(2):119-34. doi: 10.1080/009841000157014.
The effect of arsenic compounds depends on the chemical form and is specific for certain organs. The lack of specific biological indicators for the effects of each arsenic species makes it difficult to differentiate their toxicity. Five prospective biological indicators of systemic toxicity were examined at time points ranging from 15 min to 24 h using male Sprague-Dawley rats, B6C3F1 mice, Golden-Syrian hamsters, and Hartley guinea pigs, following intraperitoneal dosing with 0.1 and 1 mg/kg sodium arsenite. Rats and mice were also dosed with 1 mg/kg sodium arsenate. Total blood arsenic levels were determined in all animal species to show that exposure occurred and as an index of the severity of the change is an indicator of toxicity. Total blood arsenic levels were increased in all animal species. This increase was dose, arsenic species, and animal dependent. Renal pyruvate dehydrogenase activity was significantly decreased at early time points in mice, hamsters, and guinea pigs, and at later time points in rats dosed with arsenite. Rats and mice dosed with arsenate also exhibited PDH decrease at early time points. Blood hematocrit and glucose were increased in the rat and guinea pig, respectively, after arsenite administration. Creatinine and urea nitrogen were found to be unresponsive to arsenic in most animal species. Data suggested that the mouse and secondly the hamster appear to be the most appropriate animal models for the study of acute arsenic toxicity.
砷化合物的作用取决于其化学形式，且对特定器官具有特异性。由于缺乏针对每种砷物种作用的特异性生物指标，难以区分它们的毒性。在给雄性斯普拉格-道利大鼠、B6C3F1小鼠、金黄叙利亚仓鼠和哈特利豚鼠腹腔注射0.1和1mg/kg亚砷酸钠后，在15分钟至24小时的时间点检查了五种全身毒性的前瞻性生物指标。大鼠和小鼠还接受了1mg/kg砷酸钠的给药。测定了所有动物物种的全血砷水平，以表明暴露发生情况，并作为变化严重程度的指标，是毒性的一个指标。所有动物物种的全血砷水平均升高。这种升高取决于剂量、砷物种和动物。在小鼠、仓鼠和豚鼠的早期时间点以及给亚砷酸钠的大鼠的后期时间点，肾丙酮酸脱氢酶活性显著降低。给砷酸钠的大鼠和小鼠在早期时间点也表现出PDH降低。亚砷酸钠给药后，大鼠和豚鼠的血细胞比容和血糖分别升高。在大多数动物物种中，肌酐和尿素氮对砷无反应。数据表明，小鼠其次是仓鼠似乎是研究急性砷毒性最合适的动物模型。
