ACTIVATION AND DEGRADATION OF THE PHOSPHOROTHIONATE INSECTICIDES PARATHION AND EPN BY RAT-BRAIN
ACTIVATION AND DEGRADATION OF THE PHOSPHOROTHIONATE INSECTICIDES PARATHION AND EPN BY RAT-BRAIN
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DOI：
10.1016/0006-2952(89)90307-9
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发表时间：
1989-05-15
影响因子：
5.8
通讯作者：
CHAMBERS, JE
中科院分区：
文献类型：
--
作者：
FORSYTH, CS;CHAMBERS, JE
已知细胞色素p -450依赖的单加氧酶通过氧化脱硫将磷硫酸杀虫剂激活为氧（磷酸盐）类似物。这些激活产生了有效的抗胆碱酯酶，将大鼠脑乙酰胆碱酯酶的I50值降低了近1000倍（从10-5 M范围降至10-8M范围）。由于有机磷杀虫剂中毒导致哺乳动物死亡的常见原因是呼吸衰竭，部分原因是大脑呼吸控制中心失灵，因此我们研究了大鼠大脑激活并随后降解两种磷硫酸杀虫剂的能力，对硫磷（4-硝基苯基磷硫酸二乙基）和EPN（4-硝基苯基苯基磷硫酸乙酯）。来自雄性和雌性大鼠大脑特定区域（大脑皮层、纹状体、小脑和髓质/脑桥）和肝脏的微粒体与硫代酸和nadph生成系统孵育。通过将外源乙酰胆碱酯酶添加到孵育混合物中作为Oxon陷阱，间接地通过抑制量来定量Oxon的产生。与肝脏相比，脑组织微粒体激活特异性活性较低[分别为0.23 ~ 0.44和5.1 ~ 12.0 nmol.cntdot.min-1 (g tissue)-1]。脑线粒体部分对对硫磷的激活活性与微粒体相似[约0.35 nmol.cntdot.min-1.cntdot]。（g组织）-1]，但线粒体活性略高于微粒体活性的EPN激活[0.53 ~ 0.58和0.23 ~ 0.47 nmol .cntdot.min-1.cntdot]。(g组织)。以4-硝基苯酚产量为定量指标，测试了整个匀浆对对氧磷和EPN-oxon（4-硝基苯基苯基膦酸乙酯）的降解能力。肝脏中oxon降解的比活性高于脑[31 ~ 74]和[1.1 ~ 10.7]nmol。（g组织）-1]。总的来说，大脑和肝脏的降解活性比激活活性高1.5到12倍，这取决于所使用的化合物。这些发现表明，大脑同时具有硫代酸激活和氧的降解能力，这两种能力在暴露于有机磷杀虫剂时可能都很重要。
Cytochrome P-450-dependent monooxygenases are known to activate phosphorothionate insecticides to their oxon (phosphate) analogs by oxidative desulfuration. These activations produced potent anticholinesterases, decreasing the I50 values to rat brain acetylcholinesterase almost 1000-fold (from the 10-5 M range to the 10-8M range).Since the usual cause of death in mammals from organophosphorus insecticide poisoning is respiratory failure resulting, in part, from a failure of the respiratory control center of the brain, we investigated the ability of rat brain to activate and subsequently degrade two phosphorothionate insecticides, parathion (diethyl 4-nitrophenyl phosphorothioate) and EPN (ethyl 4-nitrophenyl phenylphosphonothioate). Microsomes from specific regions (cerebral cortex, corpus striatum, cerebellum, and medulla/pons) of the brains of male and female rats and from liver were incubated with the phosphorothionate and an NADPH-generating system. Oxon production was quantified indirectly by the amount of inhibition resulting in an exogenous source of acetylcholinesterase added to the incubation mixture as an oxon trap. The microsomal activation specific activity was low for brain when compared to liver [0.23 to 0.44 and 5.1 to 12.0 nmol.cntdot.min-1 (g tissue)-1 respectively]. The mitochondrial fraction of the brain possessed an activation activity for parathion similar to that of microsomes [about 0.35 nmol.cntdot.min-1.cntdot. (g tissue)-1 for each fraction], but mitochondrial activity was slightly greater than microsomal activity for EPN activation [0.53 to 0.58 and 0.23 to 0.47 nmole.cntdot.min-1.cntdot. (g tissue)-1]. Whole homogenates were tested for their ability to degrade paraoxon and EPN-oxon (ethyl 4-nitrophenyl phenylphosphonate), quantitated by 4-nitrophenol production. Specific activity for oxon degradation in liver was greater than that in brain [31 to 74 and 1.1 to 10.7 nmole.cntdot.min-1.cntdot. (g tissue)-1 respectively]. Overall, the brain and liver had about 1.5- to 12-fold higher specific activities for degradation than activation depending on the compound used. These findings demonstrate that the brain possesses both phosphorothionate activation and oxon degradation abilities, both of which may be significant during exposures to organophosphorus insecticides.