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首页> 外文期刊>Archives of Toxicology >Effect of organophosphorus hydrolysing enzymes on obidoxime-induced reactivation of organophosphate-inhibited human acetylcholinesterase.
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Effect of organophosphorus hydrolysing enzymes on obidoxime-induced reactivation of organophosphate-inhibited human acetylcholinesterase.

机译：有机磷水解酶对obidoxime诱导的有机磷酸酯抑制的人乙酰胆碱酯酶再活化的影响。

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摘要

The reactivation of organophosphate (OP)-inhibited acetylcholinesterase (AChE) by oximes results inevitably in the formation of highly reactive phosphyloximes (POX), which may re-inhibit the enzyme. An impairment of net reactivation by stable POX was found with 4-pyridinium aldoximes, e.g. obidoxime, and a variety of OP compounds. In this study the effect of organophosphorus hydrolase (OPH), organophosphorus acid anhydrolase (OPAA) and diisopropylfluorophosphatase (DFPase) on obidoxime-induced reactivation of human acetylcholinesterase (AChE) inhibited by different OPs was investigated. Reactivation of paraoxon-, sarin-, soman- and VX-inhibited AChE by obidoxime was impaired by POX-induced re-inhibition whereas no deviation of pseudo first-order kinetics was observed with tabun, cyclosarin and VR. OPH prevented (paraoxon) or markedly reduced the POX-induced re-inhibition (VX, sarin, soman), whereas OPAA and DFPase were without effect. Additional experiments with sarin-inhibited AChE indicate that the POX hydrolysis by OPH was concentration-dependent. The activity of OP-inhibited AChE was not affected by OPH in the absence of obidoxime. In conclusion, OPH may be a valuable contribution to the therapeutic regimen against OP poisoning by accelerating the degradation of both the parent compound, OP, and the reaction product, POX.
机译：肟对有机磷酸酯（OP）抑制的乙酰胆碱酯酶（AChE）的重新激活不可避免地导致形成高反应性的磷酸肟（POX），这可能会重新抑制该酶。发现4-吡啶醛肟（例如吡啶）对稳定POX的净再活化有损害。奥比多肟和各种OP化合物。在这项研究中，研究了有机磷水解酶（OPH），有机磷酸脱水酶（OPAA）和二异丙基氟磷酸酶（DFPase）对由不同OPs抑制的obidoxime诱导的人乙酰胆碱酯酶（AChE）的再活化的作用。 POX诱导的再抑制作用削弱了由obidoxime抑制对氧磷，沙林，梭曼和VX抑制的AChE的活性，而塔宾，环沙林和VR并未观察到假一级动力学的偏差。 OPH预防（对氧磷）或显着降低POX诱导的再抑制（VX，沙林，梭曼），而OPAA和DFPase无效。沙林抑制型AChE的其他实验表明，OPH水解POX的浓度是依赖的。在没有obidoxime的情况下，OPH不会抑制OP抑制的AChE的活性。总之，通过加速母体化合物OP和反应产物POX的降解，OPH可能是对OP中毒治疗方案的宝贵贡献。

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