1H NMR metabonomic study of rat response to tri-phenyl phosphate and tri-butyl phosphate exposure

The industrial application of organophosphates provides the opportunity for environmental exposure. While the toxicity of organophosphate compounds has been the target of significant work, studies directed towards the identification of metabolite markers to assess phosphate exposure are more limited...

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Bibliographic Details
Published in:Metabolomics 2010-09, Vol.6 (3), p.386-394
Main Authors: Alam, Todd M., Kathleen Alam, M., Neerathilingam, Muniasamy, Volk, David E., Sarkar, S., Shakeel Ansari, G. A., Luxon, Bruce A.
Format: Article
Language:English
Subjects:
Biochemistry
Biomedical and Life Sciences
Biomedicine
Cell Biology
Developmental Biology
Life Sciences
Molecular Medicine
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Summary:The industrial application of organophosphates provides the opportunity for environmental exposure. While the toxicity of organophosphate compounds has been the target of significant work, studies directed towards the identification of metabolite markers to assess phosphate exposure are more limited. In this study the urine metabolite profiles for rats following single dose exposure to either tributyl phosphate (TBP, 15 mg/kg body weight) or triphenyl phosphate (TPP, 2 and 20 mg/kg body weight) were characterized using proton nuclear magnetic resonance ( 1 H NMR) and orthogonal-partial least squares discriminate analysis (O-PLSDA). Using the developed O-PLSDA models it was possible to clearly identify TBP or TPP exposed animals. The performance of these models was validated using cross validation and permutation testing. Utilizing the variable importance in projection (VIP) coefficients from the O-PLSDA the metabolites that were most responsible for the classification of TBP or TPP exposure were determined. This initial study demonstrates the potential for NMR metabonomic studies for the identification and separation of environmental exposure to organophosphates.
ISSN:1573-3882
1573-3890
DOI:10.1007/s11306-010-0205-z