title: Metabolomics profile comparisons of irradiated and nonirradiated stored donor red blood cells.
abstract: 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.
  
  
  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 RBCs from six human donors over 35 days of storage using multilevel sparse partial least squares discriminant analysis (msPLSDA), hierarchical clustering, pathway enrichment analysis, and network analysis.
  
  
  RESULTS
  In msPLSDA analysis, RBC units stored 7 days or fewer (irradiated or nonirradiated) showed similar metabolomic profiles. By contrast, donor RBCs 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 msPLSDA 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.
  
  
  CONCLUSIONS
  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 RBCs. Metabolites involved in the cellular membrane are prominently affected and may be useful biomarkers of the RBC storage lesion.
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia; Children's Healthcare of Atlanta, Atlanta, Georgia.
authors.forename: Ravi M
authors.initials: RM
authors.lastname: Patel
authors.forename: John D
authors.initials: JD
authors.lastname: Roback
authors.forename: Karan
authors.initials: K
authors.lastname: Uppal
authors.forename: Tianwei
authors.initials: T
authors.lastname: Yu
authors.forename: Dean P
authors.initials: DP
authors.lastname: Jones
authors.forename: Cassandra D
authors.initials: CD
authors.lastname: Josephson
mesh_terms: D000225:Adenine; D001793:Blood Preservation; D002951:Citrates; D004905:Erythrocyte Aging; D004910:Erythrocyte Membrane / Q000528:radiation effects; D004912:Erythrocytes / Q000378:metabolism / Q000528:radiation effects*; D005720:Gamma Rays; D005947:Glucose; D006801:Humans; D016018:Least-Squares Analysis; D053858:Metabolic Networks and Pathways / Q000528:radiation effects; D055442:Metabolome / Q000528:radiation effects*; D008875:Middle Aged; D019999:Pharmaceutical Solutions; D010710:Phosphates; D013997:Time Factors
chemical_list: C034876:CPDA solutions; D002951:Citrates; D019999:Pharmaceutical Solutions; D010710:Phosphates; D005947:Glucose; D000225:Adenine