Optimization of Multiplate® whole blood platelet aggregometry in the Beagle dog and Wistar rat for ex vivo drug toxicity testing
Optimization of Multiplate® whole blood platelet aggregometry in the Beagle dog and Wistar rat for ex vivo drug toxicity testing
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DOI：
10.1016/j.etp.2012.07.003
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发表时间：
2013-07-01
影响因子：
--
通讯作者：
Ledieu, David
中科院分区：
文献类型：
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作者：
Defontis, Myriam;Cote, Serge;Ledieu, David
本研究旨在优化和标准化在实验室研究环境中使用的多板(R)全血阻抗聚集仪在Beagle犬和Wistar大鼠身上的使用。比较了柠檬酸、肝素和水飞蓟素的抗凝血剂，以及对ADP、胶原、花生四烯酸和PAR-4激动剂的血小板聚集反应，以确定它们在含有低浓度药物溶剂(0.1%DMSO)的血液中的半数有效浓度(EC50)。结果表明，柠檬酸抗凝不适合用于多平板(R)全血聚集，因为存在自发聚集。ADP和胶原被发现是两个物种的合适激动剂，而在Beagle犬中，PAR-4激动剂不能诱导聚集，花生四烯酸诱导的血小板聚集显示出高度的个体变异性。经计算，水飞蓟素血中激动剂的EC50值：Wistar大鼠为2.70mU M-ADP、0.85mU/ml胶原蛋白、0.03 mM花生四烯酸和165.7 mU M-PAR-4激动剂；(C)2012年爱思唯尔股份有限公司。版权所有。
This study was performed to optimize and standardize the use of the Multiplate (R) whole blood impedance aggregometer in the Beagle dog and Wistar rat for use in a research laboratory environment. The anticoagulants citrate, heparin and hirudin were compared and platelet aggregation responses to ADP, collagen, arachidonic acid and Par-4 agonist were evaluated to determine their half maximal effective concentrations (EC50) in blood containing low concentrations of a drug solvent (0.1% DMSO). The results indicate that citrate anticoagulation is not suitable for Multiplate (R) whole blood aggregometry because of the presence of spontaneous aggregation. ADP and collagen were found to be appropriate agonists for both species, whereas in the Beagle dog Par-4 agonist failed to induce aggregation and arachidonic acid induced platelet aggregation showed a high interindividual variability. The agonists EC50 calculated in hirudin blood were 2.70 mu M ADP, 0.85 mu g/ml collagen, 0.03 mM arachidonic acid and 165.7 mu M Par-4 agonist in the Wistar rat, and 0.95 mu M ADP and 0.23 mu g/ml collagen in the Beagle dog. (C) 2012 Elsevier GmbH. All rights reserved.