Ali S F, Chang L W, Slikker W
Division of Reproductive and Developmental Toxicology, National Center for Toxicological Research, Jefferson, Arkansas 72079-9502.
Biomed Environ Sci. 1991 Jun;4(1-2):207-16.
There has been a surge of interest over the past several years in the use of neurochemical endpoints to contribute to our understanding of the mechanism of action of neurotoxicants. In our present presentation, two biogenic amine systems were selected as examples of biomarkers for neurotoxicity. To investigate these neurochemical endpoints, two prototype neurotoxicants were evaluated in experimental animals. One agent, reserpine, was used to assess developmental neurotoxicity and administered prenatally, while the other, MDMA, was used in the adult animal. The neurochemical biomarkers measured were dopamine, serotonin, and their metabolite (DOPAC and 5-HIAA) concentrations by HPLC/EC and dopamine receptor binding by radioligand receptor techniques. A review of the background, experimental design, and results are presented in this article. Our findings indicate that components of the biogenic amine systems can be used as sensitive neurochemical biomarkers of neurotoxicity. These neurochemical biomarkers can be correlated with neuropathological and behavioral biomarkers to aid in the understanding of mechanisms of neurotoxicity.
在过去几年中,人们对使用神经化学终点来帮助我们理解神经毒剂的作用机制产生了浓厚兴趣。在我们目前的报告中,选择了两种生物胺系统作为神经毒性生物标志物的示例。为了研究这些神经化学终点,在实验动物中评估了两种原型神经毒剂。一种药物,利血平,用于评估发育性神经毒性并在产前给药,而另一种,摇头丸,用于成年动物。通过高效液相色谱/电化学检测法测量的神经化学生物标志物是多巴胺、血清素及其代谢物(二羟基苯乙酸和5-羟吲哚乙酸)的浓度,通过放射性配体受体技术测量多巴胺受体结合。本文介绍了背景、实验设计和结果。我们的研究结果表明,生物胺系统的成分可以用作神经毒性的敏感神经化学生物标志物。这些神经化学生物标志物可以与神经病理学和行为生物标志物相关联,以帮助理解神经毒性机制。