Application of high-throughput Fourier-transform infrared spectroscopy in toxicology studies: contribution to a study on the development of an animal model for idiosyncratic toxicity
Application of high-throughput Fourier-transform infrared spectroscopy in toxicology studies: contribution to a study on the development of an animal model for idiosyncratic toxicity
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DOI：
10.1016/j.toxlet.2003.09.011
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发表时间：
2004-02-02
影响因子：
3.5
通讯作者：
Roth, RA
中科院分区：
文献类型：
--
作者：
Harrigan, GG;LaPlante, RH;Roth, RA
对高通量傅里叶变换红外光谱 (FIF-IR) 作为一种可以支持候选药物毒理学研究中“代谢组学”组成部分的技术进行了评估。本研究测试的假设是，FT-IR 具有足够的分辨率来区分从对照大鼠群体收集的尿液和接受强效炎症剂细菌脂多糖 (LPS) 治疗的大鼠。还假设 LPS 与雷尼替丁（一种药物）共同给药与异质敏感性的报告相关，会在大鼠中引起肝毒性，并且可以通过基于 FT-IR 的代谢组学方法非侵入性地检测 LPS 与“异质”药物的共同施用代表了开发异质毒性预测模型的尝试，并且本文使用 FT-IR 来支持该模型的表征，并且使用遗传编程来识别光谱子区域。 FT-IR 快速、无需试剂、重复性高且成本低廉。这项试点研究的结果表明，它可以扩展到毒理学中的常规应用，并支持新动物模型的特殊易感性表征。(C) 2003 Elsevier Ireland Ltd. 保留所有权利。
An evaluation of high-throughput Fourier-transform infrared spectroscopy (FIF-IR) as a technology that could support a metabonomics" component in toxicological studies of drug candidates is presented. The hypothesis tested in this study was that FT-IR had sufficient resolving power to discriminate between urine collected from control rat populations and rats subjected to treatment with a potent inflammatory agent, bacterial lipopolysaccharide (LPS). It was also hypothesized that co-administration of LPS with ranitidine, a drug associated with reports of idiosyncratic susceptibility, would induce hepatotoxicity in rats and that this could be detected non-invasively by an FT-IR-based metabonomics approach. The co-administration of LPS with "idiosyncratic" drugs represents an attempt to develop a predictive model of idiosyncratic toxicity and FT-IR is used herein to support characterization of this model. FT-IR spectra are high dimensional and the use of genetic programming to identify spectral sub-regions that most contribute to discrimination is demonstrated. FT-IR is rapid, reagentless, highly reproducible and inexpensive. Results from this pilot study indicate it could be extended to routine applications in toxicology and to supporting characterization of a new animal model for idiosyncratic susceptibility. (C) 2003 Elsevier Ireland Ltd. All rights reserved.