Age-related brain cholinesterase inhibition kinetics following in vitro incubation with chlorpyrifos-oxon and diazinon-oxon.
Age-related brain cholinesterase inhibition kinetics following in vitro incubation with chlorpyrifos-oxon and diazinon-oxon.
复制标题
与毒死蜱-oxon 和二嗪磷-oxon 体外孵育后与年龄相关的脑胆碱酯酶抑制动力学。
DOI：
10.1093/toxsci/kfl123
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Timchalk,Charles
中科院分区：
文献类型：
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作者：
Kousba,AhmedA;Poet,TorkaS;Timchalk,Charles
毒死蜱和二氮磷是两种常用的有机磷杀虫剂，其主要作用机理分别是其代谢产物毒死蜱(CPO)和二氮磷(DZO)对乙酰胆碱酯酶的抑制作用。本研究的目的是通过估算双分子抑制速率常数(Ki)值来评价新生大鼠脑胆碱酯酶(ChE)对CPO和DZO的体外抑制动力学。在出生后第5天、第12天和第17天，测定CPO和DZO与新生SD大鼠脑匀浆孵育后的脑胆碱酯酶抑制和Ki值，并与成年大鼠的相应抑制和Ki值进行比较。用改良的Ellman法测定胆碱酯酶活力。从两种化合物的估算KI值可以看出，CPO对ChE的抑制作用强于DZO。新生儿脑ChE抑制动力学表现出明显的年龄敏感性，其抑制顺序为PND5>、PND7>、PND17，分别为0.95、0.50、0.22 nM−1hr−1。相反，DZO CHE抑制在新生脑组织中与年龄无关，在所有PND年龄的估计值为0.02nM−1hr−1。这些结果表明，大鼠脑ChE具有年龄和OP选择性抑制，这对于了解幼年对特定OP暴露的潜在敏感性可能是至关重要的。
Chlorpyrifos and diazinon are two commonly used organophosphorus insecticides (OPs), and their primary mechanism of action involves the inhibition of acetylcholinesterase by their metabolites chlorpyrifos-oxon (CPO) and diazinon-oxon (DZO), respectively. The study objectives were to assess thein vitroage-related inhibition kinetics of neonatal rat brain cholinesterase (ChE) for CPO and DZO by estimating the bimolecular inhibitory rate constant (ki) values. Brain ChE inhibition andkivalues following CPO and DZO incubation with neonatal Sprague-Dawley rat brain homogenates were determined at postnatal day (PND) 5, 12, and 17 and compared with the corresponding inhibition andkivalues obtained in the adult rat. A modified Ellman method was utilized for measuring the ChE activity. CPO caused a greater ChE inhibition than DZO as evidenced from the estimatedkivalues of both compounds. Neonatal brain ChE inhibition kinetics exhibited a marked age-related sensitivity to CPO, with the order of ChE inhibition being PND 5 > PND 7 > PND 17 withkivalues of 0.95, 0.50, and 0.22nM−1hr−1, respectively. In contrast, DZO ChE inhibition was not age related in the neonatal brain, and the estimatedkivalue at all PND ages was 0.02nM−1hr−1. These results demonstrated an age- and OP-selective inhibition of rat brain ChE, which may be critically important in understanding the potential sensitivity of juveniles to specific OPs exposures.