Inhibition of cholinesterase activity by isocyanates.
Inhibition of cholinesterase activity by isocyanates.
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异氰酸酯抑制胆碱酯酶活性。
DOI：
10.1016/0041-008x(82)90025-4
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发表时间：
1982
影响因子：
3.8
通讯作者：
Alarie,YC
中科院分区：
文献类型：
--
作者：
Brown,WE;Green,AH;Karol,MH;Alarie,YC
工人暴露于异氰酸酯可能导致呼吸道刺激和/或致敏。致敏的免疫学机制先前已经提出。本研究探讨了异氰酸酯的毒性呼吸作用是否可能是由于其抑制胆碱酯酶的能力，这是刺激反应的一种可能机制。六亚甲基二异氰酸酯（HDI）、异氰酸己酯（HI）和2，6-甲苯二异氰酸酯（2，6-TDI）以4：1至8：1（异氰酸酯：酶）的摩尔比加入时被发现完全抑制纯化的人血清胆碱酯酶。相比之下，2，4-甲苯二异氰酸酯（2，4-TDI）、异氰酸苯酯或异氰酸邻甲苯酯对50%酶的抑制需要50：1或更大的摩尔比。酶抑制作用也通过将纯化的胆碱酯酶暴露于含有1 ppm异氰酸酯的气氛中来实现。在这些条件下，HDI和HI再次是最有效的酶抑制剂，而2，4-TDI和2，6-TDI显示出的反应性要小得多。在生理条件下，当整个人血浆是胆碱酯酶的来源时，HDI和HI仍然是有效的酶抑制剂。然而，对于后两种异氰酸酯，实现50%酶抑制所需的摩尔浓度表明这些试剂的亲和标记。HDI和HI显示的强效胆碱酯酶抑制作用可能为暴露于这些异氰酸酯后观察到的呼吸道炎症提供了解释。
Exposure of workers to isocyanates may result in irritation and/or sensitization of the respiratory tract. An immunologic mechanism for sensitization has been presented previously. This investigation explored whether, as a possible mechanism for the irritation reaction, the toxic respiratory effect of isocyanates might be due to their ability to inhibit cholinesterases. Hexamethylene diisocyanate (HDI), hexyl isocyanate (HI), and 2,6-toluene diisocyanate (2,6-TDI) were found to completely inhibit purified human serum cholinesterase when added at molar ratios of 4:1 to 8:1 (isocyanate:enzyme). By contrast, molar ratios of 50:1 or greater were required for 50% enzyme inhibition by 2,4-toluene diisocyanate (2,4-TDI), phenyl isocyanate, or o-tolyl isocyanate. Enzyme inhibition was also achieved by exposure of purified cholinesterase to atmospheres containing 1 ppm isocyanates. Under these conditions, HDI and HI were again the most potent enzyme inhibitors with much less reactivity shown by 2,4-TDI and 2,6-TDI. Under more physiologic conditions, when whole human plasma was the source of cholinesterase, HDI and HI were still potent enzyme inhibitors. However, with the latter two isocyanates, the molar concentrations needed to effect 50% enzyme inhibition suggested affinity labeling by these reagents. The potent cholinesterase inhibition shown by HDI and HI may offer explanation for observed respiratory symptomatology noted upon exposure to these isocyanates.
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发表时间：
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DOI：
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期刊：
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