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二氯甲烷、1,3-二氯丙烷和1,2-二氯苯对大鼠闪光诱发电位(FEP)的急性神经活性作用比较。

A comparison of the acute neuroactive effects of dichloromethane, 1,3-dichloropropane, and 1,2-dichlorobenzene on rat flash evoked potentials (FEPs).

作者信息

Herr D W, Boyes W K

机构信息

National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.

出版信息

Fundam Appl Toxicol. 1997 Jan;35(1):31-48. doi: 10.1006/faat.1996.2255.

Abstract

Previous research showed that acute exposure to dichloromethane (DCM) produced a selective reduction in peak N30 of flash evoked potentials (FEPs) in rats. In contrast, acute exposures to p-xylene or toluene selectively reduced FEP peak N160. The present experiments compared the effects of DCM (log P = 1.25; oil:water partition coefficient), 1,3-dichloropropane (DCP; log P = 2.00), and 1,2-dichlorobenzene (DCB; log P = 3.38) on FEPs recorded from adult Long-Evans rats. Before administration of test compounds, FEPs were recorded for five daily sessions to develop FEP peak N160. Test compounds were dissolved in corn oil and administered i.p. at doses based on proportions of their LD50 values. The doses were: DCM, 0, 57.5, 115, 230, or 460 mg/kg; DCP, 0, 86, 172, 343, or 686 mg/kg; and DCB, 0, 53, 105, 210, or 420 mg/kg. Testing times after dosing varied among compounds and were based on pilot studies to measure both the times of peak effect and recovery. Each solvent produced significant changes in the latency and amplitude of multiple components of the FEP waveforms. However, the predominant effect of DCM was to reduce the amplitude of peak N30 (ED50 = 326.3 mg/kg), that of DCP was to reduce both peaks N30 (ED50 = 231.0 mg/kg) and N160 (ED50 = 136.8 mg/kg), and that of DCB was to reduce peak N160 (ED50 = 151.6 mg/kg). There was no consistent relationship between log P values and the potency of the compounds to alter FEP peaks N30 and N160. The results suggest that organic solvents have multiple acute effects on the function of the central nervous system, which are not predictable solely by the compound's lipid solubility.

摘要

先前的研究表明,急性暴露于二氯甲烷(DCM)会使大鼠闪光诱发电位(FEP)的N30峰值出现选择性降低。相比之下,急性暴露于对二甲苯或甲苯会选择性降低FEP的N160峰值。本实验比较了DCM(log P = 1.25;油:水分配系数)、1,3 - 二氯丙烷(DCP;log P = 2.00)和1,2 - 二氯苯(DCB;log P = 3.38)对成年Long - Evans大鼠记录的FEP的影响。在给予受试化合物之前,连续五天每天记录FEP以得出FEP的N160峰值。受试化合物溶于玉米油并按其半数致死量(LD50)值的比例腹腔注射给药。剂量分别为:DCM,0、57.5、115、230或460 mg/kg;DCP,0、86、172、343或686 mg/kg;DCB,0、53、105、210或420 mg/kg。给药后的测试时间因化合物而异,基于预实验研究来测量效应峰值时间和恢复时间。每种溶剂都会使FEP波形多个成分的潜伏期和波幅产生显著变化。然而,DCM的主要作用是降低N30峰值的波幅(半数有效剂量[ED50] = 326.3 mg/kg),DCP的主要作用是降低N30(ED50 = 231.0 mg/kg)和N160(ED50 = 136.8 mg/kg)两个峰值,DCB的主要作用是降低N160峰值(ED50 = 151.6 mg/kg)。log P值与化合物改变FEP的N30和N160峰值的效力之间没有一致的关系。结果表明,有机溶剂对中枢神经系统功能有多种急性影响,不能仅通过化合物的脂溶性来预测这些影响。

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