391 Cutaneous Host Metabolomic Alterations after Burn Injury in a Murine Model

Abstract

Metabolomics is the study of the biological pathways affected by the unique metabolites of an organism. This field has been extensively researched in many pathological processes such as cancer and blunt/penetrating trauma, but knowledge of the effects of thermal injury on the metabolome is comparatively limited. The aim of this study is to investigate the regulation of metabolites after an extensive thermal injury in a murine model to better understand the resulting tissue damage and identify potential therapeutic targets. Depilated mice were subjected to 30% total body surface area (TBSA) burn by submersion in 100⁰C water. Skin biopsies were taken on euthanasia at 2, 6 and 24 hours after injury (n=3 for all time points). An equal number of mice had sham procedures and biopsy collection for each time point. Samples were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Multivariate analysis, the principal components analysis (PCA), was calculated using R and to validate metabolic changes. Two hours after burn injury, differential regulation between injured and sham animals was found in 4495 metabolites. Of these, 1733 metabolites achieved statistically significant difference (p<0.05). These metabolites have the greatest impact on the linoleic acid metabolism pathway. At hours 6 and 24, 1528 and 1924 metabolites respectively were differentially regulated with statistical significance. At hour 6, linoleic acid metabolism was again the most affected pathway. At hour 24, D-glutamine and D-arginine pathways were the most affected. Comparing all burned animals to all sham animals, 728 metabolites were differentially regulated. Pathways containing a significant number of these common elements include arachidonic acid, starch and sucrose metabolism. Thermal injury induces changes in the metabolome of mice that are evident in skin biopsies. The continual involvement of the arachidonic acid pathway highlights the inflammatory process that occurs in the 24 hours after burn injury. The common changes in starch and sucrose metabolic pathways reflects the hypermetabolism that results from burns. The dynamic process of burn injury response is revealed in the variability of differentially regulated metabolites at each time point. Further, the pathways most affected at hour 24 differ from those at the earlier time points, which are more closely associated with inflammation. Future research will determine the potential of using skin biopsies in human patients after thermal injury to investigate metabolomic changes. Early recognition of these alterations may help influence clinical interventions to promote appropriate inflammatory response and long-term healing.