肟硫磷的毒物代谢动力学和毒效学

Toxicokinetics and toxicodynamics of phoxim in rats

采用高效液相色谱法 ,测定血清和脑组织匀浆中的肟硫磷 ,揭示其经口染毒 SD大鼠体内的毒物代谢动力学过程 ;以血清丁酰胆碱酯酶 (BCh E)和脑组织乙酰胆碱酯酶 (ACh E)的抑制率及一氧化氮合酶 (NOS)活性为毒效应指标 ,阐明肟硫磷的毒效动力学特征 .给大鼠 ig肟硫磷 2 75mg·kg-1后 ,血清毒物浓度 -时间曲线符合一级吸收一室开放模型 ,ka= 1 .87h-1,Tp=1 .2 6h,Cmax=1 .90 mg· L-1.ACh E抑制效应与血清肟硫磷浓度之间呈逆时针滞后环 .脑组织中 NOS活性随时间进程的异常波动 ,提示 NO参与产生非胆碱能神经毒作用 . BCh E抑制以后不能迅速自动恢复 ,所致酶的“老化”。

The biological samples were ex- tracted with ethylacetate and concentrated. Employing the high performance liquid chromatography with a reverse- phase chro- matographic column of Lichrosorb Si 6 0 and a mobile phase of tetrahydrofuran/petroleum ether (1 .4/98.6 ) for determina- tion of phoxim content in serum and brain homogenate,the toxicokinetic profile of phoxim administrated orally in rats was il- lustrated.Meanwhile,using the inhibition rate of serum butyrylcholinesterase(BCh E) activity and brain homogenate acetyl- cholinesterase (ACh E) activity as well as the activity of nitric oxide synthase(NOS) in brain homogenate as toxic effect indices, its toxicodynamics was explored.Toxicoki- netic studies of phoxim in rat after2 75 mg · kg- 1 intragastic administration demon- strated that serum phoxim concentration against time profile was fitted well to the one- compartmentopen model with1 st order absorption. Toxicokinetic parameters and their values calculated from this model were ka1 .87h- 1 ,t1 / 2 (ka) 0 .37h,Tp1 .2 6 h,Cmax1 . 90 mg· L- 1 .Relationship between in- hibitory effect on ACh E and serum phoxim concentration was indicated as a counter- clock- wise hysteresis loop. The abnormal fluctuation of NOS activity in brain,with the time prolonging,indicated that NO in- volved in the non- cholinergic neurotoxicity. These results,rather slower auto- reactiva- tion and aging of inhibited BCh E,may sug- gest pronounced evidence for its role in cholinergic effect.