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急性甲苯暴露与大鼠视觉功能与瞬间脑内浓度成正比。

Acute toluene exposure and rat visual function in proportion to momentary brain concentration.

作者信息

Boyes William K, Bercegeay Mark, Krantz Quentin Todd, Kenyon Elaina M, Bale Ambuja S, Shafer Timothy J, Bushnell Philip J, Benignus Vernon A

机构信息

Neurotoxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.

出版信息

Toxicol Sci. 2007 Oct;99(2):572-81. doi: 10.1093/toxsci/kfm172. Epub 2007 Jul 10.

Abstract

Acute exposure to toluene was assessed in two experiments to determine the relationship between brain toluene concentration and changes in neurophysiological function. The concentration of toluene in brain tissue at the time of assessment was estimated using a physiologically based pharmacokinetic model. Brain neurophysiological function was measured using pattern-elicited visual evoked potentials (VEP) recorded from electrodes located over visual cortex of adult male Long-Evans rats. In the first experiment, VEPs were recorded before and during exposure to control air or toluene at 1000 ppm for 4 h, 2000 ppm for 2 h, 3000 ppm for 1.3 h, or 4000 ppm for 1 h. In the second experiment, VEPs were recorded during and after exposure to clean air or 3000 or 4000 ppm toluene. In both experiments, the response amplitude of the major spectral component of the VEP (F2 at twice the stimulus rate in steady-state responses) was reduced by toluene. A logistic function was fit to baseline-adjusted F2 amplitudes from the first experiment that described a significant relationship between brain toluene concentration and VEP amplitude deficits. In the second experiment, 3000 ppm caused equivalent VEP deficits during or after exposure as a function of estimated brain concentration, but 4000 ppm showed a rapid partial adaptation to the acute effects of toluene after exposure. In general, however, the neurophysiological deficits caused by acute toluene exposure could be described by estimates of the momentary concentration of toluene in the brain at the time of VEP evaluation.

摘要

在两项实验中评估了急性甲苯暴露情况,以确定脑内甲苯浓度与神经生理功能变化之间的关系。评估时脑组织中的甲苯浓度使用基于生理的药代动力学模型进行估算。脑神经生理功能通过从成年雄性Long-Evans大鼠视觉皮层上方电极记录的模式诱发视觉诱发电位(VEP)来测量。在第一个实验中,在暴露于对照空气或1000 ppm甲苯4小时、2000 ppm甲苯2小时、3000 ppm甲苯1.3小时或4000 ppm甲苯1小时之前和期间记录VEP。在第二个实验中,在暴露于清洁空气或3000或4000 ppm甲苯期间及之后记录VEP。在两项实验中,甲苯均降低了VEP主要频谱成分(稳态反应中刺激频率两倍时的F2)的反应幅度。对第一个实验中经基线调整的F2幅度拟合了一个逻辑函数,该函数描述了脑内甲苯浓度与VEP幅度缺陷之间的显著关系。在第二个实验中,3000 ppm在暴露期间或之后根据估计的脑浓度导致了等效的VEP缺陷,但4000 ppm在暴露后显示出对甲苯急性效应的快速部分适应。然而,总体而言,急性甲苯暴露引起的神经生理缺陷可以通过VEP评估时脑内甲苯瞬间浓度的估计来描述。

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