HYDROLYSIS AND BINDING OF A TOXIC STEREOISOMER OF SOMAN IN PLASMA AND TISSUE-HOMOGENATES FROM RAT, GUINEA-PIG AND MARMOSET, AND IN HUMAN PLASMA
HYDROLYSIS AND BINDING OF A TOXIC STEREOISOMER OF SOMAN IN PLASMA AND TISSUE-HOMOGENATES FROM RAT, GUINEA-PIG AND MARMOSET, AND IN HUMAN PLASMA
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DOI：
10.1016/0006-2952(93)90106-7
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发表时间：
1993-10-19
影响因子：
5.8
通讯作者：
BENSCHOP, HP
中科院分区：
文献类型：
--
作者：
DEJONG, LPA;VANDIJK, C;BENSCHOP, HP
梭曼的两种异构体之一（1，2，2-三甲基丙基甲基膦酰氟）的浓度下降，即，在血浆和大鼠、豚鼠和绒猴的脑、肺、肝、肾、膈肌、骨骼肌和小肠粘膜匀浆以及人血浆（pH 7.5，37度）中研究了C（+）P（-）-梭曼。异构体浓度降低后，通过气相色谱法测定残留浓度，由于异构体的共价结合位点非常快速饱和，然后进行催化水解，因此分两个阶段进行。 获得了共价结合位点浓度的估计值，其在肝脏和肾脏中相对较高。 从第二反应阶段评价异构体从40 ng/mL浓度水解至20 ng/mL的时间段。可以得出结论，在参与中枢消除的器官中发现的C（+）P（-）-梭曼降解的自发和酶催化水解活性足够高，足以解释我们在2-6 LD 50 C（+/-）P（+/-）-梭曼中毒后血药浓度的毒代动力学研究中发现的异构体的终末半衰期。梭曼毒性作用靶器官的水解活性较低，隔膜和大脑，特别是豚鼠和绒猴。
The fallen concentration of one of the two isomers of soman (1,2,2-trimethylpropyl methylphosphonofluoridate), i.e., C(+)P(-)-soman, was investigated in plasma and in homogenates of brain, lung, liver, kidney, diaphragm, skeletal muscle and mucosa of small intestines from rat, guinea pig and marmoset, and in human plasma (pH 7.5, 37-degrees). The decrease of the isomer concentration was followed by gas chromatographic determination of the residual concentration and proceeded in two phases due to a very rapid saturation of covalent binding sites for the isomer followed by catalysed hydrolysis. Estimates for the concentrations of covalent binding sites were obtained, which were relatively high in liver and kidney. Time periods for the hydrolysis of the isomer from a concentration of 40 ng/mL to 20 ng/mL were evaluated from the second reaction phase. It is concluded that the spontaneous and enzyme-catalyzed hydrolytic activities found for degradation of C(+)P(-)-soman in organs participating in central elimination are sufficiently high to account for the terminal half-life times of the isomer found in our toxicokinetic studies for the blood concentration after intoxication with 2-6 LD50 C(+/-)P(+/-)-soman. The hydrolytic activities are lower in the target organs for toxic action of soman, e.g., diaphragm and brain, especially for guinea pigs and marmosets.