Modifications induced by chemical skin allergens on the metabolome of reconstructed human epidermis: A pilot high-resolution magic angle spinning nuclear magnetic resonance study.

Publisher: Wiley Country of Publication: England NLM ID: 7604950 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1600-0536 (Electronic) Linking ISSN: 01051873 NLM ISO Abbreviation: Contact Dermatitis Subsets: MEDLINE

Publication: <2005-> : Oxford : Wiley
Original Publication: Copenhagen, Munksgaard.

Metabolome*; Allergens/*toxicity ; Dermatitis, Allergic Contact/*metabolism ; Epidermis/*metabolism ; Magnetic Resonance Spectroscopy/*methods; Biomarkers/metabolism ; Dermatitis, Allergic Contact/etiology ; Discriminant Analysis ; Humans ; Multivariate Analysis ; Pilot Projects ; Skin Irritancy Tests

Background: High-resolution magic angle spinning (HRMAS) is a nuclear magnetic resonance (NMR) technique that enables the characterization of metabolic phenotypes/metabolite profiles of cells, tissues, and organs, under both normal and pathological conditions, without resorting to time-consuming extraction techniques.
Objectives: To assess the impact of chemical skin sensitizers vs non-sensitizers on the metabolome of three-dimensional reconstructed human epidermis (RHE) by HRMAS NMR.
Methods: Based on the SENS-IS assay, 12 skin sensitizers and five non-sensitizing chemicals were investigated and applied on EpiSkin RHE at the published maximal non-irritating concentrations under the conditions of the test. The metabolome of RHE samples was then analyzed by HRMAS NMR.
Results: A total of 32 different metabolites were identified; 20 of these were quantified for all samples. Statistical univariate analysis showed that the tissue content of most measured metabolites (with the exception of acetate and glucose) was different in the untreated, treated with non-sensitizers, and treated with sensitizers samples. In RHE samples in contact with sensitizing chemicals, concentrations of 18 metabolites were significantly decreased. Alanine and tyrosine could not discriminate between sensitizer- and non-sensitizer-treated groups. A multivariate partial least-squares-discriminant analysis was performed on the two treated groups, discriminating sensitizing and non-sensitizing chemicals with a very good R2Y value of 0.87 and a good Q2Y value of 0.70.
Conclusions: Data suggest that HRMAS NMR could be used to monitor the impact of chemicals, skin allergens vs non-sensitizers, on the metabolome of three-dimensional RHE.
(© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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This research was supported in part by a research grant of L'Oréal, France.

Keywords: HRMAS NMR; chemical skin allergens; metabolome; reconstructed human epidermis

0 (Allergens)
0 (Biomarkers)

Date Created: 20191017 Date Completed: 20201123 Latest Revision: 20201123

20250114

10.1111/cod.13415

31617582