The effect of diethyldithiocarbamate on brain uptake of cadmium.
The effect of diethyldithiocarbamate on brain uptake of cadmium.
复制标题
二乙基二硫代氨基甲酸酯对大脑镉摄取的影响。
DOI：
10.1016/0041-008x(82)90262-9
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发表时间：
1982
影响因子：
3.8
通讯作者：
Klaassen,CD
中科院分区：
文献类型：
--
作者：
CantilenaJr,LR;Irwin,G;Preskorn,S;Klaassen,CD
先前对小鼠的一项研究表明，螯合剂二乙基二硫代氨基甲酸盐（DDC）在用于治疗镉中毒时，会增加大脑中金属的浓度。进行了研究，以证实大鼠的这些发现，并确定所观察到的影响的机制。DDC（10 mg/kg，ip）给雄性Sprague-Dawley大鼠颈动脉内镉给药前30分钟，导致增加了10倍，在单程脑提取镉。研究了两种可能的机制来解释这一观察结果。首先，DDC通过中枢肾上腺素能机制可能导致脑毛细血管通透性（CCP）对扩散限制物质的普遍增加，或可能减少脑血流量（CBF），从而延长脑循环通过时间。第二，DDC ma6螯合Cd以形成对血脑屏障（BBB）更具渗透性的复合物。CBF由脑摄取的[14C]丁醇与静脉注射示踪剂后以恒定速率抽取的动脉血样中的[14C]丁醇的比率确定。CCP通过双扩散示踪技术确定为Ew（水的提取分数）。DDC没有改变任何参数，这表明DDC-Cd相互作用的机制可能涉及形成一个复杂的更渗透到血脑屏障。这一结论得到了以下发现的支持：在CdCl2溶液中加入DDC使Cd（作为DDC-Cd络合物）的辛醇-水分配系数增加了375倍。
A previous study in mice has shown that the chelating agent diethyldithiocarbamate (DDC), when used to treat intoxication with cadmium, increased the concentration of the metal in brain. Studies were undertaken to confirm these findings in rats and to determine the mechanism of the observed effect. DDC (10 mg/kg, ip) given to male Sprague-Dawley rats 30 min prior to intracarotid Cd administration resulted in a 10-fold increase in the single pass cerebral extraction of cadmium. Two possible mechanisms were studied to explain this observation. First, DDC via a central adrenergic mechanism may cause a generalized increase in cerebral capillary permeability (CCP) to a diffusion-limited substance or may reduce cerebral blood flow (CBF) thereby prolonging cerebral circulatory transit time. Second, DDC ma6 chelate Cd to form a complex more permeable to the blood:brain barrier (BBB). CBF was determined from the ratio of [14C]butanol taken up by the brain to the [14C]butanol in an arterial blood sample withdrawn at a constant rate following iv injection of the tracer. CCP was determined as Ew(extraction fraction of water) by the double-diffusion tracer technique. DDC did not alter either parameter, suggesting that the mechanism of the DDC-Cd interaction may involve the formation of a complex more permeable to the BBB. This conclusion is supported by the finding that the addition of DDC to a CdCl2solution increased the octanol-water partition coefficient of Cd (as DDC-Cd complex) by 375-fold.