Padilla S, Wilson V Z, Bushnell P J
Cellular and Molecular Toxicology Branch, United States Environmental Protection Agency, Research Triangle Park, NC 27711.
Toxicology. 1994 Sep 6;92(1-3):11-25. doi: 10.1016/0300-483x(94)90164-3.
Inhibition of cholinesterase activity in the blood has been proposed as an index of ChE activity in tissues targeted by ChE-inhibiting pesticides, including the muscle end-plate region and the central nervous system (CNS). While opinions vary regarding the utility of blood ChE activity in predicting ChE activity in the target tissues, there appear to be no comprehensive studies designed to assess this possible correlation in a time- and dose-dependent manner. We undertook this type of study by administering a single dose of an organophosphate, chlorpyrifos (0, 30, 60 or 125 mg/kg in corn oil, s.c.) to rats and then sacrificing animals at 1, 4, 7, 21 or 35 days after dosing. Whole blood, plasma, erythrocytes, frontal cortex, hippocampus, striatum, hypothalamus and diaphragm tissue were collected and assayed for ChE activity. Collapsed across dosages, optimal correlations of blood ChE activity with brain or muscle activity occurred 7-21 days after dosing (when ChE inhibition was maximal and most stable). At all times after dosing, there was a high correlation among ChE activity in the hippocampus, striatum and frontal cortex. Generally, ChE activity in whole blood and erythrocytes correlated better with the activity in brain and muscle than did activity in the plasma (whole blood > or = erythrocytes >> plasma). Similar relationships were also observed in a more abbreviated study using a direct acting organophosphate, paraoxon. ChE activity was determined in blood components, brain and muscle at the time of maximal inhibition (4 h after injection) and during recovery (24 hrs after injection) using two dosage levels (0.17 or 0.34 mg/kg, s.c.). Taken together, these data indicate that the level of ChE activity in the blood may accurately reflect activity in other tissues, but that this correlation is tissue- and time-specific.
血液中胆碱酯酶活性的抑制已被提议作为胆碱酯酶抑制性农药作用靶点组织（包括肌肉终板区域和中枢神经系统）中胆碱酯酶活性的指标。尽管对于血液胆碱酯酶活性在预测靶组织中胆碱酯酶活性的效用存在不同观点，但似乎尚无旨在以时间和剂量依赖性方式评估这种可能相关性的全面研究。我们通过给大鼠单次皮下注射有机磷农药毒死蜱（0、30、60或125毫克/千克，溶于玉米油），然后在给药后1、4、7、21或35天处死动物，进行了此类研究。收集全血、血浆、红细胞、额叶皮质、海马体、纹状体、下丘脑和膈肌组织，并检测胆碱酯酶活性。综合各剂量来看，血液胆碱酯酶活性与脑或肌肉活性的最佳相关性出现在给药后7 - 21天（此时胆碱酯酶抑制作用最大且最稳定）。在给药后的所有时间点，海马体、纹状体和额叶皮质中的胆碱酯酶活性之间都存在高度相关性。一般来说，全血和红细胞中的胆碱酯酶活性与脑和肌肉中的活性相关性比血浆中的更好（全血≥红细胞>>血浆）。在一项使用直接作用有机磷农药对氧磷的更简略研究中也观察到了类似关系。在最大抑制时（注射后4小时）和恢复期间（注射后24小时），使用两个剂量水平（0.17或0.34毫克/千克，皮下注射）测定血液成分、脑和肌肉中的胆碱酯酶活性。综上所述，这些数据表明血液中胆碱酯酶活性水平可能准确反映其他组织中的活性，但这种相关性是组织和时间特异性的。
