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Sun, N. ; Fernandez, I.E. ; Wei, M. ; Witting, M. ; Aichler, M. ; Feuchtinger, A. ; Burgstaller, G. ; Verleden, S.E.* ; Schmitt-Kopplin, P. ; Eickelberg, O. ; Walch, A.K.

Pharmacometabolic response to pirfenidone in pulmonary fibrosis detected by MALDI-FTICR-MSI.

Eur. Respir. J. 52:1702314 (2018)
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Idiopathic pulmonary fibrosis (IPF) is a fatal condition that reduces life expectancy and shows a limited response to available therapies. Pirfenidone has been approved for treatment of IPF, but little is known about the distinct metabolic changes that occur in the lung upon pirfenidone administration.Here, we performed a proof-of-concept study using high-resolution quantitative matrix-assisted laser desorption/ionisation Fourier-transform ion cyclotron resonance mass spectrometry imaging (MALDI-FTICR-MSI) to simultaneously detect, visualise and quantify in situ endogenous and exogenous metabolites in lungs of mice subjected to experimental fibrosis and human patients with IPF, and to assess the effect of pirfenidone treatment on metabolite levels.Metabolic pathway analysis and endogenous metabolite quantification revealed that pirfenidone treatment restores redox imbalance and glycolysis in IPF tissues, and downregulates ascorbate and aldarate metabolism, thereby likely contributing to in situ modulation of collagen processing. As such, we detected specific alterations in metabolite pathways in fibrosis and, importantly, metabolic recalibration following pirfenidone treatment.Together, these results highlight the suitability of high-resolution MALDI-FTICR-MSI for deciphering the therapeutic effects of pirfenidone and provide a preliminary analysis of the metabolic changes that occur during pirfenidone treatment in vivo These data may therefore contribute to improvement of currently available therapies for IPF.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Imaging Mass-spectrometry; High-resolution; Lung-diseases; Ascorbic-acid; Metabolites; Segmentation; Activation; Mechanisms; Diagnosis; Bleomycin
Language english
Publication Year 2018
HGF-reported in Year 2018
ISSN (print) / ISBN 0903-1936
e-ISSN 1399-3003
Journal European Respiratory Journal
Quellenangaben Volume: 52, Issue: 3, Pages: , Article Number: 1702314 Supplement: ,
Publisher European Respiratory Society
Publishing Place Sheffield
Reviewing status Peer reviewed
Institute(s) Research Unit Analytical Pathology (AAP)
Institute of Lung Health and Immunity (LHI)
Research Unit BioGeoChemistry and Analytics (BGC)
CF Pathology & Tissue Analytics (CF-PTA)
POF-Topic(s) 30205 - Bioengineering and Digital Health
30202 - Environmental Health
30505 - New Technologies for Biomedical Discoveries
Research field(s) Enabling and Novel Technologies
Lung Research
Environmental Sciences
PSP Element(s) G-500390-001
G-501600-001
G-504800-001
G-501600-014
A-630600-001
DOI 10.1183/13993003.02314-2017
WOS ID WOS:000452391500003
Scopus ID 85063941671
PubMed ID 30072508
Erfassungsdatum 2018-08-05
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