Alteration in Circulating Metabolites During and After Heat Stress in the Conscious Rat: Potential Biomarkers of Exposure and Organ-specific Injury
ARMY CENTER FOR ENVIRONMENTAL HEALTH RESEARCH FORT DETRICK MD
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Background Heat illness is a debilitating and potentially life-threatening condition. Limited data are available to identify individuals with heat illness at greatest risk for organ damage. We recently described the transcriptomic and proteomic responses to heat injury and recovery in multiple organs in an in vivo model of conscious rats heated to a maximum core temperature of 41.8 C Tc,Max. In this study, we examined changes in plasma metabolic networks at Tc,Max, 24, or 48 hours after the heat stress stimulus. Results Circulating metabolites were identified by gas chromatographymass spectrometry and liquid chromatographytandem mass spectrometry. Bioinformatics analysis of the metabolomic data corroborated proteomics and transcriptomics data in the tissue at the pathway level, supporting modulations in metabolic networks including cell death or catabolism pyrimidine and purine degradation, acetylation, sulfation, redox alterations and glutathione metabolism, and the urea cyclecreatinine metabolism, energetics stasis in glycolysis and tricarboxylic acid cycle, -oxidation, cholesterol and nitric oxide metabolism, and bile acids. Hierarchical clustering identified 15 biochemicals that differentiated animals with histopathological evidence of cardiac injury at 48 hours from uninjured animals. The metabolic networks perturbed in the plasma corroborated the tissue proteomics and transcriptomics pathway data, supporting a model of irreversible cell death and decrements in energetics as key indicators of cardiac damage in response to heat stress. Conclusions Integrating plasma metabolomics with tissue proteomics and transcriptomics supports a diagnostic approach to assessing individual susceptibility to organ injury and predicting recovery after heat stress.
- Anatomy and Physiology
- Medicine and Medical Research