INHIBITION OF HUMAN-SERUM COMPLEMENT ACTIVITY BY DIISOPROPYLFLUOROPHOSPHATE AND SELECTED ANTICHOLINESTERASE INSECTICIDES
INHIBITION OF HUMAN-SERUM COMPLEMENT ACTIVITY BY DIISOPROPYLFLUOROPHOSPHATE AND SELECTED ANTICHOLINESTERASE INSECTICIDES
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DOI：
10.1016/0272-0590(89)90020-1
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发表时间：
1989-04-01
期刊：
影响因子：
--
通讯作者：
CONNOLLY, JJ
中科院分区：
文献类型：
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作者：
CASALE, GP;BAVARI, S;CONNOLLY, JJ
人类补体（C“）系统是抵抗感染的主要防线，其激活需要丝氨酸酯酶的参与。由于广泛使用的抗胆碱酯酶杀虫剂抑制丝氨酸酯酶，本研究评估了西维因，克百威，敌敌畏，对氧磷抑制C“活性的正常人血清的面板的效力。用改良的测定法测量了C“-介导的绵羊红细胞裂解，（1）掺入了次优浓度的致敏抗体，（2）对丝氨酸外切酶抑制剂表现出增加的敏感性。在掺入C“反应混合物之前2小时，将测试化学品加入稀释的血清中。将抑制C“和血清胆碱酯酶（CHE）的效力与二异丙基氟磷酸盐（DFP）的效力进行比较，DFP是一种有效的丝氨酸酯酶抑制剂和C”酯酶的标准探针。在0.5至3.0 mM，西维因，克百威，敌敌畏，和DFP产生了剂量依赖性的抑制溶解，而对氧磷没有抑制作用。在摩尔基础上，西维因是三倍更有效的DFP，并抑制裂解15-25和26-45%，分别在1.0和3.0 mM。克百威、敌敌畏和DFP的效力相等。DFP、对氧磷、敌敌畏、克百威和西维因抑制CHE（职业暴露于有机磷酸酯和氨基甲酸酯的标志物）的平均IC 50为1.0 × 10 - 6。10-8，4.1 ×10-8，1.0 ×10-7，3.3 ×10-6和1.8倍。10-5 M，分别。杀虫剂抑制CHE的效力不能预测抑制血清C“活性的绝对或相对效力。
Activation of the human complement (C'') system, a major line of defense against infections, requires the participation of serine esterases. Since the widely used anticholinesterase insecticides inhibit serine esterases, the present study evaluated potencies of carbaryl, carbofuran, dichlorvos, and paraoxon to inhibit C'' activities of a panel of normal human sera. C''-mediated lysis of sheep red cells was measured with a modified assay (1) incorporating suboptimal concentrations of sensitizing antibody and (2) exhibiting increased sensitivity to serine exterase inhibitors. Test chemicals were added to diluted sera 2 hr prior to incorporation into C'' reaction mixtures. Potencies to inhibit C'' and serum cholinesterase (CHE) were compared to potencies of diisopropylfluorophosphate (DFP), a potent serine esterase inhibitor and a standard probe for C'' esterases. At 0.5 to 3.0 mM, carbaryl, carbofuran, dichlorvos, and DFP produced a dose-dependent inhibition of lysis, whereas paraoxon was not inhibitory. On a molar basis, carbaryl was three times more potent than DFP, and inhibited lysis 15-25 and 26-45% at 1.0 and 3.0 mM, respectively. Carbofuran, dichlorvos, and DFP were equipotent. Mean IC50''s for inhibition of CHE (a marker for occupational exposure to organophosphates and carbamates) by DFP, paraoxon, dichlorvos, carbofuran, and carbaryl were 1.0 .times. 10-8, 4.1 .times. 10-8, 1.0 .times. 10-7, 3.3 .times. 10-6, and 1.8 .times. 10-5 M, respectively. Potencies of the insecticides to inhibit CHE did not predict absolute or relative potencies to inhibit serum C'' activity.