Contribution towards a metabolite profile of the detoxification of benzoic acid through glycine conjugation: an intervention study
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Date
2016Author
Irwin, Cindy
Van Reenen, Mari
Mason, Shayne
Mienie, Lodewyk J.
Reinecke, Carolus J.
Westerhuis, Johan A.
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Benzoic acid is widely used as a preservative in food products and is detoxified in humans
through glycine conjugation. Different viewpoints prevail on the physiological significance of
the glycine conjugation reaction and concerns have been raised on potential public health
consequences following uncontrolled benzoic acid ingestion. We performed a metabolomics
study which used commercial benzoic acid containing flavored water as vehicle for designed
interventions, and report here on the controlled consumption of the benzoic acid by 21
cases across 6 time points for a total of 126 time points. Metabolomics data from urinary
samples analyzed by nuclear magnetic resonance spectroscopy were generated in a timedependent
cross-over study. We used ANOVA-simultaneous component analysis (ASCA),
repeated measures analysis of variance (RM-ANOVA) and unfolded principal component
analysis (unfolded PCA) to supplement conventional statistical methods to uncover fully the
metabolic perturbations due to the xenobiotic intervention, encapsulated in the metabolomics
tensor (three-dimensional matrices having cases, spectral areas and time as axes).
Identification of the biologically important metabolites by the novel combination of statistical
methods proved the power of this approach for metabolomics studies having complex data
structures in general. The study disclosed a high degree of inter-individual variation in detoxification
of the xenobiotic and revealed metabolic information, indicating that detoxification
of benzoic acid through glycine conjugation to hippuric acid does not indicate glycine depletion,
but is supplemented by ample glycine regeneration. The observations lend support to
the view of maintenance of glycine homeostasis during detoxification. The study indicates
also that time-dependent metabolomics investigations, using designed interventions, provide
a way of interpreting the variation induced by the different factors of a designed experiment–an
approach with potential to advance significantly our understanding of normal and
pathophysiological perturbations of endogenous or exogenous origin
URI
http://hdl.handle.net/10394/19922https://doi.org/10.1371/journal.pone.0167309
http://journals.plos.org/plosone/article/authors?id=10.1371/journal.pone.0167309