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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

Toxicology Letters, 146(3): 197--205, 2004.
Authors: George G. Harrigan and Roxanne H. LaPlante and Greg N. Cosma and Gary Cockerell and Royston Goodacre and Jane F. Maddox and James P. Luyendyk and Patricia E. Ganey and Robert A. Roth
Tags: Bacterial High-throughput Idiosyncratic Metabonomics algorithms, genetic infrared lipopolysaccharide, programming, spectroscopy, toxicity,
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.
| BibTeX  
@article{harrigan:2004:TXL,
title = {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},
author = {George G. Harrigan and Roxanne H. LaPlante and Greg N. Cosma and Gary Cockerell and Royston Goodacre and Jane F. Maddox and James P. Luyendyk and Patricia E. Ganey and Robert A. Roth},
journal = {Toxicology Letters},
month = {2 February},
number = {3},
pages = {197--205},
volume = {146},
year = {2004},
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.},
notes = {Pharmacia Corporation, GMax-Bio}, doi = {doi:10.1016/j.toxlet.2003.09.011},
keywords = {Bacterial High-throughput Idiosyncratic Metabonomics algorithms, genetic infrared lipopolysaccharide, programming, spectroscopy, toxicity, }
}