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Experimental colitis and malnutrition differentially affect the metabolism of glutathione and related sulfhydryl metabolites in different tissues

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Abstract

Purpose

Inflammatory bowel diseases (IBD) are characterized by severe inflammation within the gastrointestinal (GI) tract. This inflammation is known to drive the catabolism of protein in the affected tissue and modulate systemic protein metabolism. Yet despite the established increase in oxidative stress and changes in protein catabolism, little is known as to the effects of IBD on metabolism of glutathione (GSH) and related metabolites. The aim of this study was to conduct a comprehensive analysis of the response of GSH and related sulfhydryl metabolites to malnutrition and GI inflammation. We hypothesized that the inflammatory stress of colitis would decrease the concentration and the synthesis of GSH in various tissues of well-nourished piglets. Additionally, the superimposition of malnutrition on colitis would further decrease glutathione status.

Methods

Healthy, well-nourished piglets were compared to those receiving dextran sulphate sodium-induced, a macronutrient-restricted diet or both. The synthesis of GSH was determined by primed constant infusion of [15N,13C2]glycine and tandem mass spectrometry analysis. Additionally, the concentrations of GSH and related sulfhydryl metabolites were also determined by UHPLC–tandem mass spectrometry—a novel analytic technique.

Results

In healthy piglets, GSH synthesis was highest in the liver, along with the concentrations of both cysteine and γ-glutamylcysteine. Piglets with colitis had decreased synthesis of GSH and decreased concentrations of GSH, cysteine and γ-glutamylcysteine in the distal colon compared to healthy controls. Additionally, there was no change with superimposition of malnutrition on colitis in the distal colon.

Conclusion

Synthesis and metabolism of GSH are uniquely regulated in each tissue. Colitis, independent of nutrition, compromises GSH status and the concentration of cysteine in the distal colon of piglets with GI inflammation. The techniques developed in this study have translational applications and can be scaled for use in clinical investigation of GI inflammation.

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Acknowledgments

Funding

Partially funded by: (1) Natural Sciences and Engineering Research Council of Canada Grant Number 183710-09 (Wykes), (2) Canadian Foundation for Innovation Grant Number 23910 (Wykes) and (3) McGill University Graduate Excellence Fellowship (Vassilyadi).

Author contributions

All authors read and approved the final manuscript. Vassilyadi, Harding, Nitschmann and Wykes designed the research; Harding conducted the animal trial and isotope infusions; Vassilyadi and Nitschmann performed mass spectrometry; Vassilyadi performed statistical analysis; Vassilyadi, Harding, Nitschmann and Wykes wrote the paper; and Wykes had primary responsibility for the final content.

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Authors and Affiliations

  1. School of Dietetics and Human Nutrition, Macdonald Campus, McGill University, Montreal, QC, H9X 3V9, Canada

    Photios Vassilyadi, Scott V. Harding, Evan Nitschmann & Linda J. Wykes

  2. Diabetes and Nutritional Sciences Division, School of Medicine, King’s College London, London, SE1 9NH, UK

    Scott V. Harding

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  1. Photios Vassilyadi
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Correspondence to Linda J. Wykes.

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Vassilyadi, P., Harding, S.V., Nitschmann, E. et al. Experimental colitis and malnutrition differentially affect the metabolism of glutathione and related sulfhydryl metabolites in different tissues. Eur J Nutr 55, 1769–1776 (2016). https://doi.org/10.1007/s00394-015-0995-x

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  • DOI: https://doi.org/10.1007/s00394-015-0995-x

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