Quantitative determination of dithiocarbamates in human plasma, serum, erythrocytes and urine: pharmacokinetics of broccoli sprout isothiocyanates in humans
Quantitative determination of dithiocarbamates in human plasma, serum, erythrocytes and urine: pharmacokinetics of broccoli sprout isothiocyanates in humans
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DOI：
10.1016/s0009-8981(01)00727-6
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发表时间：
2002-02-01
影响因子：
5
通讯作者：
Talalay, P
中科院分区：
文献类型：
--
作者：
Ye, LX;Dinkova-Kostova, AT;Talalay, P
背景：人类从蔬菜中接触到大量的异硫氰酸酯和硫代葡萄糖苷。由于膳食异硫氰酸酯被广泛认为是潜在的重要抗癌化学保护剂，因此测量异硫氰酸酯及其二硫氨基甲酸酯代谢物的血浆和组织药代动力学的可靠方法对于确定给药方案至关重要。方法：异硫氰酸酯（ITC）和二硫氨基甲酸酯（DTC）与1,2-苯二硫醇定量反应生成1,3-苯二硫醇-2-硫酮。尽管这种环缩合反应在分析植物材料和尿液样本方面非常有用，但血液和组织中DTC/ITC（样品中参与环缩合反应的DTC和ITC成分的总量）的测定一直受到低水平和高浓度蛋白质干扰环缩合反应的阻碍。通过聚乙二醇（PEG）沉淀或超滤可降低血液和组织中的蛋白质含量，通过固相萃取环缩合产物可大大提高方法的灵敏度。结果：对四名志愿者进行了药代动力学测量，他们接受了单次剂量约200 μ mol的西兰花芽异硫氰酸酯（主要是萝卜硫素，少量的叶黄素和蓖麻素）。异硫氰酸酯吸收迅速，在饲喂后1 h达到血浆、血清和红细胞浓度峰值0.943 ~ 2.27 μ mol/l，并呈一级动力学下降（半衰期为1.77 +/- 0.13 h）。8时的累积排泄量为剂量的58.3 +/- 2.8%。清除率为369±53 ml/min，提示肾小管分泌活跃。结论：建立了一种灵敏、特异的测定人血浆、血清和红细胞中DTC含量的方法。ITC/DTC水平的测定很重要，因为：(i)饮食中的异硫氰酸酯在降低癌症风险方面具有潜在价值，（ii）人类作为杀菌剂、杀虫剂、杀虫剂和橡胶硫化促进剂广泛接触DTC。(C) 2002 Elsevier Science B.V.版权所有
Background: Humans are exposed to substantial quantities of isothiocyanates and glucosinolates from vegetables. Since dietary isothiocyanates are widely regarded as potentially important chemoprotectors against cancer, reliable methods for measuring the plasma and tissue pharmacokinetics of isothiocyanates and their dithiocarbamate metabolites are essential for defining dosing regimens. Methods: Isothiocyanates (ITC) and dithiocarbamates (DTC) react quantitatively with 1,2-benzenedithiol to produce 1,3-benzodithiole-2-thione that can be quantified spectroscopically. Although this cyclocondensation reaction has been highly useful for analyzing plant material and urine samples, the determination of DTC/ITC (the total quantity of DTC and ITC components in a sample that react in the cyclocondensation reaction) in blood and tissues has been hampered by their low levels and the high concentrations of proteins that interfere with the cyclocondensation reaction. The protein content of blood and tissues was reduced by the precipitation with polyethylene glycol (PEG) or ultrafiltration, and the sensitivity of the method was increased substantially by the solid phase extraction of the cyclocondensation product. Results: Pharmacokinetic measurements were made in four human volunteers who received single doses of about 200 mumol of broccoli sprout isothiocyanates (largely sulforaphane, with lesser amounts of iberin and erucin). Isothiocyanates were absorbed rapidly, reached peak concentrations of 0.943-2.27 mumol/l in plasma, serum and erythrocytes at 1 h after feeding and declined with first-order kinetics (half-life of 1.77 +/- 0.13 h). The cumulative excretion at 8 It was 58.3 +/- 2.8% of the dose. Clearance was 369 +/- 53 ml/min, indicating active renal tubular secretion. Conclusion: A sensitive and specific method for quantifying DTC levels in human plasma, serum, and erythrocytes has been devised. Determinations of ITC/DTC levels are important because: (i) dietary isothiocyanates are of potential value in reducing the risk of cancer, and (ii) humans are extensively exposed to DTC as fungicides, insecticides, pesticides and rubber vulcanization accelerators. (C) 2002 Elsevier Science B.V. All rights reserved.