A metabonomic investigation of hepatotoxicity using diffusion-edited 1H NMR spectroscopy of blood serum.
It has been shown extensively, that chemometric investigations of 1H NMR spectra of rat urine taken from animals dosed with model toxins produce characteristic patterns of metabolic responses and that this permits the identification of biomarkers of toxic response and regeneration. To date, metabonomic methods have been mainly optimised for urine which contains mainly low molecular weight moieties, and thus a conventional 1-dimensional 1H NMR pulse sequence is an efficient means of obtaining information-rich data. In the case of biofluids such as blood plasma or serum, which contain a wide range of macromolecules the resonances of which can overlap with peaks from small molecule metabolites, the information giving rise to sample classification can be concealed in a conventional NMR spectrum andthis presents a different analytical challenge in terms of chemometric analysis of spectral profiles. Here, the use of other types of NMR data have been investigated and it is shown that by using spectra where the peak intensities are edited according to their molecular diffusion coefficients, it is possible to improve differentiation of control animals and those treated with the model hepatotoxin, alpha-naphthylisothiocyanate (ANIT). By using diffusion-edited spectroscopy, plasma lipid moieties are less attenuated than those from small endogenous metabolites and thus the toxin-induced changes to the lipoprotein profiles are more easily detectable.
Beckwith-Hall
Bridgette M
BM
Biological Chemistry, Biomedical Sciences Division, Imperial College London, Sir Alexander Fleming Building, South Kensington, London, UK SW7 2AZ.
Thompson
Nicholas A
NA
Nicholson
Jeremy K
JK
Lindon
John C
JC
Holmes
Elaine
E
D015058:1-Naphthylisothiocyanate; D000818:Animals; D015415:Biomarkers / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury; D008074:Lipoproteins / Q000097:blood*; D008107:Liver Diseases / Q000097:blood*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D025341:Principal Component Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D015415:Biomarkers; D008074:Lipoproteins; D015058:1-Naphthylisothiocyanate