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
| Autor: | Royston Goodacre, Roxanne H LaPlante, Greg N Cosma, George G. Harrigan, James P. Luyendyk, Jane F. Maddox, Patricia E. Ganey, Gary L. Cockerell, Robert A. Roth |
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| Rok vydání: | 2003 |
| Předmět: |
Drug
Lipopolysaccharides Male media_common.quotation_subject Analytical chemistry Pilot Projects Computational biology High dimensional Toxicology Ranitidine Toxicology studies Rats Sprague-Dawley Disease susceptibility Animal model Spectroscopy Fourier Transform Infrared Toxicity Tests Animals media_common Chemistry Liver Diseases Discriminant Analysis General Medicine Idiosyncratic toxicity Rats Sprague dawley Histamine H2 Antagonists Toxicity Models Animal Disease Susceptibility Chemical and Drug Induced Liver Injury |
| Zdroj: | Toxicology letters. 146(3) |
| ISSN: | 0378-4274 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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