Application of metabonomics in a compound ranking study in early drug development revealing drug-induced excretion of choline into urine

Chemical Research in Toxicology

Volumn 19, Issue 9, 2006, Pages 1175-1181

  Dieterle, Frank ^a   Schlotterbeck, Götz ^a   Ross, Alfred ^a   Niederhauser, Urs ^a   Senn, Hans ^a  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

CHOLINE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL MEMBRANE; CONTROLLED STUDY; KIDNEY TUBULE ABSORPTION; MALE; METABOLOMICS; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; OXIDATION; RAT; URINALYSIS; URINARY EXCRETION;

ANIMALS; CHOLINE; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DESIGN; MAGNETIC RESONANCE SPECTROSCOPY; MALE; RATS; RATS, WISTAR;

ANIMALIA;

EID: 33749012286     PISSN: 0893228X     EISSN: None     Source Type: Journal    
DOI: 10.1021/tx060094b     Document Type: Article

References (35)

1. Fiehn, O. (2002) Metabolomics-The link between genotypes and phenoty pes. Plant Mol. Biol. 48, 155-171.
2. Trethewey, R. N., Krotzky, A. J., and Willmitzer, L. (1999) Metabolic profiling: A rosetta stone for genomics? Curr. Opin. Plant Biol. 2, 83-85.
3. Nicholson, J. K., Lindon, J. C., and Holmes, E. (1999) "Metabonomics": Understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data. Xenobiotica 29, 1181-1189.
4. Lindon, J. C., Nicholson, J. K., Holmes, E., and Everett, J. R. (2000) Metabonomics: Metabolic processes studied by NMR spectroscopy of biofluids. Concepts Magn. Reson. 12, 289-320.
5. Nicholson, J. K., Connelly, J., Lindon, J. C., and Holmes, E. (2002) Metabonomics: A platform for studying drug toxicity and gene function. Nat. Rev. Drug Discovery 1, 153-161.
6. Shockcor, J. P., and Holmes, E. (2002) Metabonomic applications in toxicity screening and disease diagnosis. Curr. Top. Med. Chem. 2, 35-51.
7. Nicholson, J. K., and Wilson, I. D. (2003) Understanding 'global' systems biology: Metabonomics and the continuum of metabolism. Nat. Rev. Drug Discovery 2, 668-676.
8. Fernie, A. R., Tretewey, R. N., Krotzky, A. J., and Willmitzer, L. (2004) Metabolite profiling: From diagnostics to systems biology. Nat. Rev. Mol. Cell Biol. 5, 1-7.
9. Lindon, J. C., Homes, E., Bollard, M. E., Stanley E. G., and Nicholson, J. K. (2004) Metabonomics technologies and their applications in physiological monitoring, drug safety assessment and disease diagnosis. Biomarkers 9, 1-31.
10. Bollard, M. E., Stanley, E. G., Lindon, J. C., Nicholson, J. K., and Holmes, E. (2005) NMR-based metabonomic approaches for evaluating physiological influences on biofluid composition. NMR Biomed. 18, 143-162.
11. Bugrim, A., Nikolskaya, T., and Nikolsky, Y. (2004) Early prediction of drug metabolism and toxicity: Systems biology approach and modeling. Drug Discovery Today 9, 127-135.
12. 1H-NMR metabonomics. Anal. Chem. 78, 4281-4290.
13. Bell, J. D., Sadler, P. J., Morris, V. C., and Levander, O. A. (1991) Effect of aging and diet on proton NMR spectra of rat urine. Magn. Reson. Med. 17, 414-422.
14. Palmer, A. G., III, Cavanagh, J., Wright, P. E., and Rance, M. (1991) Sensitivity improvement in proton-detected two-dimensional heteronuclear correlation spectroscopy. J. Magn. Reson. 93, 151-170.
15. Shaka, A. J., Barker, P. B., and Freemann, R. (1985) Computer optimized decoupling scheme for wideband applications and low level operation. J. Magn. Reson. 64, 547-552.
16. 1H NMR data sets. Anal. Chem. 77, 1282-1289.
17. Williams, R. E., Eyton-Jones, H. W., Farnworth, M. J., Gallagher, R., and Provan, W. M. (2002) Effect of intestinal microflora on the urinary metabolic profile of rates: A 1H-nuclear magnetic resonance spectroscopy study. Xenobiotica 32, 783-794.
18. Gavaghan, C. L., Nicholson, J. K., Connor, S. C., Wilson, I. D., Wright, B., and Holmes, E. (2001) Directly coupled high- performance liquid chromatography and nuclear magnetic resonance spectroscopic with chemometric studies on metabolic variation in sprague- dawley rats. Anal. Biochem. 291, 245-252.
19. Bell, J. D., Sadler, P. J., Morris, V. C., and Levander, O. A. (1991) Effect of aging and diet on proton NMR spectra of rat urine. Magn. Reson. Med. 17, 414-422.
20. Willimans, R. E., Lenz, E. M., Lowden, J. S., Rantalainen, M., and Wilson, I. D. (2005) The metabonomics of aging and development in the rat: An investigation into the effect of age o the profile of endogenous metabolites in the urine of male rats using 1H NMR and HPLC-TOF MS. Mol. Biosyst. 1, 166-175.
21. Unpublished "Food Deprivation Study" of the COMET project. More details about the COMET project are in Lindon, J. C., Nicholson, J. K., Holmes, E., Antti, H., Bollard, M. E., and Keun, H., et al. (2003) Contemporary issues in toxicology: The role of metabonomics in toxicology and its evaluation by the COMET project. Toxicol. Appl. Pharmacol. 187, 137-146.
22. Buchmann, A. L., Jenden, D., and Roch, M. (1999) Plasma free, phopholipid-Bound and urinary free choline all decrease during a marathon run and may be associated with impaired performance. J. Am. Coll. Nutr. 18, 598-601.
23. Da Costa, K. A., Garner, S. C., Chang, J., and Zeisel, S. H. (1995) Effects of prolonged (1 year) choline deficiency and subsequent refeeding of choline on 1, 2-sn-diradylglycerol, fatty acids and protein kinase C in rat liver. Carcinogenesis 16, 327-334.
24. Newberne, P. M., and Rogers, A. E. (1986) Labile methyl groups and the promotion of cancer. Annu. Rev. Nutr. 6, 407-432.
25. Best, C. H., and Lucas, C. C. (1943) Choline-Chemistry and significance as a dietary factor. Vitam. Horm. 1, 1-58.
26. Lohr, J. W., Wilsky, G. R., and Acara, M. A. (1999) Renal drug metabolism. Pharmacol. Rev. 50, 107-141.
27. Griffin, J. L., Mann, C. J., Scott, J., Shoulders, C. C., and Nicholson, J. K. (2001) Choline containing metabolites during cell transfection: An insight into magnetic resonance spectroscopy detectable changes. FEBS Lett. 509, 263-266.
28. Waters, N. J., Holmes, E., Williams, A., Waterfielsd, C. J., Farrant, R. D., and Nicholson, J. K. (2001) NMR and pattern recognition studies on the time-related metabolic effects of α-naphthylisothiocyanate on liver, urine, and plasma in the rat: An integrative metabonomic approach. Chem. Res. Toxicol. 14, 1401-1412.
29. 1H NMR spectroscopic analysis in toxicology studies to determine inherent variation in biochemical profiles. J. Pharm. Biomed. Anal. 30, 1297-1310.
30. Coen, M., Lenz, E. M., Nicholson, J. K., Wilson, I. D., Pognan, F., and Lindon, J. C. (2003) An integrated metabonomic investigation of acetaminophen toxicity in the mouse using NMR spectroscopy. Chem. Res. Toxicol. 16, 295-303.
31. Coen, M., Ruepp, S. U., Lindon, J. C., Nicholson, J. K., Pognan, F., Lenz, E. M., and Wilson, I. D. (2004) Integrated application of transcriptomics and metabonomics yields new insight into the toxicity due to paracetamol in the mouse. J. Pharm. Biomed. Anal. 35, 93-105.
32. Acara, M., and Rennick, B. (1973) Regulation of plasma choline by the renal tubule: Bidirectional transport of choline. Am. J. Physiol. 225, 1123-1128.
33. Acara, M., Roch-Ramel, F., and Rennick, B. (1979) Bidirectional renal tubular transport of free choline: A micropuncture study. Am. J. Physiol. 236, 112-118.
34. Luecke, R. W., and Pearson, P. B. (1944) The microbiological determination of free choline in plasma and urine. J. Biol. Chem. 153, 259-263.
35. Morishire-Smith, R. J., Skiles, G. L., Lawrence, J. W., Spence, S., Nicholls, A. W., Johnson, B. A., and Nicholson, J. K. (2004) Use of metabonomics to identify impaired fatty acid metabolism as the mechanism of a drug-induced toxicity. Chem. Res. Toxicol. 17, 165-173.