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Metabolomics profile comparisons of irradiated and nonirradiated stored donor red blood cells
Author(s) -
Patel Ravi M.,
Roback John D.,
Uppal Karan,
Yu Tianwei,
Jones Dean P.,
Josephson Cassandra D.
Publication year - 2015
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.12884
Subject(s) - metabolomics , irradiation , arachidonic acid , linoleic acid , metabolic pathway , chemistry , metabolism , biology , biochemistry , fatty acid , chromatography , enzyme , physics , nuclear physics
Background Understanding the metabolites that are altered by donor red blood cell ( RBC ) storage and irradiation may provide insight into the metabolic pathways disrupted by the RBC storage lesion. Study Design and Methods Patterns of metabolites, representing more than 11,000 distinct mass‐to‐charge ratio ( m / z ) features, were compared between gamma‐irradiated and nonirradiated CPDA ‐1–split RBC s from six human donors over 35 days of storage using multilevel sparse partial least squares discriminant analysis (ms PLSDA ), hierarchical clustering, pathway enrichment analysis, and network analysis. Results In ms PLSDA analysis, RBC units stored 7 days or fewer (irradiated or nonirradiated) showed similar metabolomic profiles. By contrast, donor RBC s stored 10 days or more demonstrated distinct clustering as a function of storage time and irradiation. Irradiation shifted metabolic features to those seen in older units. Hierarchical clustering analysis identified at least two clusters of metabolites that differentiated between RBC units based on storage time and irradiation exposure, confirming results of the ms PLSDA analysis. Pathway enrichment analysis, used to map the discriminatory biochemical features to specific metabolic pathways, identified four pathways significantly affected by irradiation and/or storage including arachidonic acid (p = 3.3 × 10 −33 ) and linoleic acid (p = 1.61 × 10 −11 ) metabolism. Conclusion RBC storage under blood bank conditions produces numerous metabolic alterations. Gamma irradiation accentuates these differences as the age of blood increases, indicating that at the biochemical level irradiation accelerates metabolic aging of stored RBC s. Metabolites involved in the cellular membrane are prominently affected and may be useful biomarkers of the RBC storage lesion.