Jones R D, Hamilton B F, Dass P D
Toxicology Department, Miles Inc., Stilwell, KS 66085-9104, USA.
Vet Res Commun. 1995;19(2):135-47. doi: 10.1007/BF01839280.
The purpose of the study was to correlate electroretinogram (ERG) parameters with increasing levels of plasma, erythrocyte and ocular tissue cholinesterase inhibition using the beagle dog as a model for human neurovisual toxicity. The anticholinesterase compound physostigmine was administered at various steady-state intravenous infusion rates based on pharmacokinetic estimates of plasma and red blood cell cholinesterase inhibition. The most sensitive parameter was the b-wave amplitude of the rod response, which was significantly depressed compared to pretreatment at all levels of acute cholinesterase depression. The overall maximal ERG response demonstrated a trend of declining a- and b-wave amplitudes, which corresponded with the increased levels of cholinesterase depression, but these differences were not significant. The depression of the electroretinogram rod and cone amplitudes appeared to parallel plasma cholinesterase inhibition more closely than erythrocyte cholinesterase activity. Ocular tissue cholinesterase activity was significantly depressed in the retina (70%), cornea (60%) and dorsal rectus extraocular muscle (46%). Electroretinography may be a useful physiological tool for evaluating the ocular toxicity of certain chemicals or pharmaceuticals associated with cholinesterase biomarker activity.
本研究的目的是以比格犬作为人类神经视觉毒性模型，将视网膜电图（ERG）参数与血浆、红细胞和眼组织胆碱酯酶抑制水平的升高相关联。根据血浆和红细胞胆碱酯酶抑制的药代动力学估计，以不同的稳态静脉输注速率给予抗胆碱酯酶化合物毒扁豆碱。最敏感的参数是视杆细胞反应的b波振幅，在急性胆碱酯酶抑制的所有水平下，与预处理相比均显著降低。总体最大ERG反应显示出a波和b波振幅下降的趋势，这与胆碱酯酶抑制水平的增加相对应，但这些差异并不显著。视网膜电图视杆细胞和视锥细胞振幅的降低似乎比红细胞胆碱酯酶活性更紧密地平行于血浆胆碱酯酶抑制。眼组织胆碱酯酶活性在视网膜（70%）、角膜（60%）和眼外直肌背侧（46%）中显著降低。视网膜电图可能是一种有用的生理工具，用于评估与胆碱酯酶生物标志物活性相关的某些化学物质或药物的眼毒性。
