The effects of CaNa(2)EDTA on brain lead mobilization in rodents determined using a stable lead isotope tracer.
The effects of CaNa(2)EDTA on brain lead mobilization in rodents determined using a stable lead isotope tracer.
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使用稳定铅同位素示踪剂测定 CaNa(2)EDTA 对啮齿动物脑铅动员的影响。
DOI：
10.1006/taap.1999.8725
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Smith,DR
中科院分区：
文献类型：
--
作者：
Seaton,CL;Lasman,J;Smith,DR
研究证明 CaNa2EDTA 可有效降低血液和软组织（包括大脑）中的铅 (Pb) 水平。然而，人们仍然担心，由于内源性铅的重新分布，单剂量的 CaNa2EDTA 可能会导致脑内铅水平显着升高。在这里，我们利用 Pb 暴露的啮齿动物模型结合敏感的稳定 Pb 同位素示踪剂方法来评估 CaNa2EDTA 螯合治疗对 Pb 在脑、血液、肾脏和骨组织中重新分布的影响。 32 只成年雌性白化大鼠（n = 6-7 只动物/组）暴露于含 100 μg Pb/mL 的饮用水中 4 周。通过腹膜内注射施用稳定的204Pb示踪剂。螯合前 2 天注射。 CaNa2EDTA 腹膜内施用。剂量为 150 mg/kg/天，持续 1 至 5 天。用单变量方差分析评估统计差异。在此处使用的铅暴露和螯合治疗方案下，没有证据表明在单次CaNa 2 EDTA剂量后内源性铅（作为总铅或不稳定204Pb示踪剂）可测量地重新分布到大脑中。此外，CaNa 2 EDTA在可测量地降低脑或骨Pb水平方面并不有效，尽管不稳定20 4 Pb示踪剂的脑水平在螯合5天后显着降低。 CaNa2EDTA 治疗可有效显着降低血液和肾脏的 Pb 水平。总体而言，这些数据证实了 CaNa2EDTA 对于降低软组织 Pb 水平（但不是总脑 Pb）的功效，并且它们不支持对治疗后脑 Pb 水平短暂增加的担忧。
Studies have demonstrated the efficacy of CaNa2EDTA for reducing lead (Pb) levels in blood and soft tissues, including brain. However, a concern remains that a single dose of CaNa2EDTA may cause a significant increase in brain Pb levels due to a redistribution of endogenous Pb. Here we utilized a rodent model of Pb exposure in combination with a sensitive stable Pb isotope tracer methodology to assess the effects of CaNa2EDTA chelation treatment on the redistribution of Pb in brain, blood, kidney, and bone tissues. Thirty-two adult female albino rats (n = 6–7 animals/group) were exposed to 100 μg Pb/mL in drinking water for 4 weeks. Stable204Pb tracer was administered via i.p. injection over 2 days prior to chelation. CaNa2EDTA was administered i.p. at a dose of 150 mg/kg/day for 1 to 5 days. Statistical differences were evaluated with univariate ANOVA. Under the Pb exposure and chelation treatment regimens utilized here, there was no evidence of a measurable redistribution of endogenous Pb (as total Pb or labile204Pb tracer) into the brain after a single CaNa2EDTA dose. Further, CaNa2EDTA was not efficacious in measurably reducing brain or bone Pb levels, although brain levels of labile204Pb tracer were significantly reduced after 5 days of chelation. CaNa2EDTA treatment was effective in significantly reducing both blood and kidney Pb levels. Overall, these data substantiate the efficacy of CaNa2EDTA for reducing soft tissue Pb levels, but not total brain Pb, and they do not support concern for a transient increase in brain Pb levels with treatment.