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 language | English |
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Pages (from-to) | 197-205 |
Number of pages | 8 |
Journal | Toxicology Letters |
Volume | 146 |
Issue number | 3 |
DOIs | |
Publication status | Published - 2 Feb 2004 |
Keywords
- Bacterial lipopolysaccharide
- High-throughput infrared spectroscopy
- Idiosyncratic toxicity
- Metabonomics