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

George G. Harrigan, Roxanne H. LaPlante, Greg N. Cosma, Gary Cockerell, Royston Goodacre, Jane F. Maddox, James P. Luyendyk, Patricia E. Ganey, Robert A. Roth

    Research output: Contribution to journalArticlepeer-review

    Abstract

    An evaluation of high-throughput Fourier-transform infrared spectroscopy (FT-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. © 2003 Elsevier Ireland Ltd. All rights reserved.
    Original languageEnglish
    Pages (from-to)197-205
    Number of pages8
    JournalToxicology Letters
    Volume146
    Issue number3
    DOIs
    Publication statusPublished - 2 Feb 2004

    Keywords

    • Bacterial lipopolysaccharide
    • High-throughput infrared spectroscopy
    • Idiosyncratic toxicity
    • Metabonomics

    Fingerprint

    Dive into the research topics of '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'. Together they form a unique fingerprint.

    Cite this