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Blood donor exposome and impact of common drugs on red blood cell metabolism.
- Source :
-
JCI insight [JCI Insight] 2021 Feb 08; Vol. 6 (3). Date of Electronic Publication: 2021 Feb 08. - Publication Year :
- 2021
-
Abstract
- Computational models based on recent maps of the RBC proteome suggest that mature erythrocytes may harbor targets for common drugs. This prediction is relevant to RBC storage in the blood bank, in which the impact of small molecule drugs or other xenometabolites deriving from dietary, iatrogenic, or environmental exposures ("exposome") may alter erythrocyte energy and redox metabolism and, in so doing, affect red cell storage quality and posttransfusion efficacy. To test this prediction, here we provide a comprehensive characterization of the blood donor exposome, including the detection of common prescription and over-the-counter drugs in blood units donated by 250 healthy volunteers in the Recipient Epidemiology and Donor Evaluation Study III Red Blood Cell-Omics (REDS-III RBC-Omics) Study. Based on high-throughput drug screenings of 1366 FDA-approved drugs, we report that approximately 65% of the tested drugs had an impact on erythrocyte metabolism. Machine learning models built using metabolites as predictors were able to accurately predict drugs for several drug classes/targets (bisphosphonates, anticholinergics, calcium channel blockers, adrenergics, proton pump inhibitors, antimetabolites, selective serotonin reuptake inhibitors, and mTOR), suggesting that these drugs have a direct, conserved, and substantial impact on erythrocyte metabolism. As a proof of principle, here we show that the antacid ranitidine - though rarely detected in the blood donor population - has a strong effect on RBC markers of storage quality in vitro. We thus show that supplementation of blood units stored in bags with ranitidine could - through mechanisms involving sphingosine 1-phosphate-dependent modulation of erythrocyte glycolysis and/or direct binding to hemoglobin - improve erythrocyte metabolism and storage quality.
- Subjects :
- Adolescent
Adult
Aged
Animals
Energy Metabolism drug effects
Erythrocyte Transfusion
Female
Glycolysis drug effects
Healthy Volunteers
Hemoglobins metabolism
High-Throughput Screening Assays
Humans
In Vitro Techniques
Machine Learning
Male
Metabolomics
Mice
Mice, Inbred C57BL
Mice, Knockout
Middle Aged
Models, Biological
Oxidation-Reduction drug effects
Phosphotransferases (Alcohol Group Acceptor) deficiency
Phosphotransferases (Alcohol Group Acceptor) genetics
Ranitidine pharmacology
Young Adult
Blood Donors
Erythrocytes drug effects
Erythrocytes metabolism
Exposome
Nonprescription Drugs adverse effects
Nonprescription Drugs pharmacokinetics
Prescription Drugs adverse effects
Prescription Drugs pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 2379-3708
- Volume :
- 6
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- JCI insight
- Publication Type :
- Academic Journal
- Accession number :
- 33351786
- Full Text :
- https://doi.org/10.1172/jci.insight.146175