Gale G R, Atkins L M, Walker E M, Smith A B
Ann Clin Lab Sci. 1983 Sep-Oct;13(5):425-31.
Diethyldithiocarbamate (DDTC) and diethylenetriaminepentaacetate (DTPA) were assessed to determine if combination treatment with these two chelators of different chemical classes would enhance mobilization and excretion of metallothionein-bound cadmium (Cd) from selected organs of mice which had earlier received 0.03 mg of CdCl2 . 2.5 H2O along with 1.0 microCi of 109Cd. In addition to measuring individual organ radioactivity after seven and after 13 injections of each compound individually as well as in combination, whole body Cd burden was measured, and the routes and rates of Cd excretion were determined. When used alone, DDTC was effective in mobilizing Cd from kidney, liver, intestine, and spleen. The DTPA when used alone was not consistently effective in reducing Cd burdens in any of the organs assessed. Coadministration of DDTC and DTPA promoted an enhancement of Cd mobilization from liver, kidney, spleen, and intestine over that which was observed with DDTC alone. When DTPA was administered with DDTC, it did not prevent accumulation of Cd in lung and brain which was observed upon treatment with DDTC alone. Combined treatment did produce a more marked depletion of total body 109Cd burden than did the administration of DDTC alone. A more rapid rate of both fecal and urinary excretion of Cd was observed when the chelators were coadministered. It was concluded that at least an additive or possibly supraadditive effect may be obtained by combining a dithiocarbamate chelator with one of the aminocarboxylate class in total body Cd decorporation.
评估二乙基二硫代氨基甲酸盐(DDTC)和二乙烯三胺五乙酸(DTPA),以确定用这两种不同化学类别的螯合剂联合治疗是否会增强从早期接受过0.03mg CdCl₂·2.5H₂O和1.0微居里¹⁰⁹Cd的小鼠选定器官中动员和排泄与金属硫蛋白结合的镉(Cd)的能力。除了在分别单独以及联合注射每种化合物7次和13次后测量各个器官的放射性外,还测量了全身Cd负荷,并确定了Cd的排泄途径和速率。单独使用时,DDTC能有效地从肾脏、肝脏、肠道和脾脏中动员Cd。单独使用DTPA时,在评估的任何器官中都不能始终如一地有效降低Cd负荷。DDTC和DTPA联合给药比单独使用DDTC时能促进从肝脏、肾脏、脾脏和肠道中动员更多的Cd。当DTPA与DDTC一起给药时,它并不能阻止在单独用DDTC治疗时观察到的Cd在肺和脑中的积累。联合治疗确实比单独给予DDTC更显著地降低了全身¹⁰⁹Cd负荷。当螯合剂联合给药时,观察到Cd的粪便和尿液排泄速率更快。得出的结论是,在全身Cd的去除中,将二硫代氨基甲酸盐螯合剂与一种氨基羧酸盐类螯合剂联合使用至少可以获得相加或可能超相加的效果。