A serum metabolomics signature of hypothermia fatalities involving arginase activity, tryptophan content, and phosphatidylcholine saturation

Abstract

The serum metabolic signature of hypothermia fatalities herein observed pointed toward metabolic adaptations that likely aimed at heat production enhancement, endothelial function, and cell membrane fluidity preservation. Novel biomarkers potentially useful in a hypothermia diagnosis were also identified.

Biomarkers of Cerebral Damage in Fatal Hypothermia

“…There is no morphological (whether it be radiological, macroscopic, or microscopic) or biochemical (whether it be metabolic, or metabolomic) finding that allows, at least at the current state of knowledge and when considered individually and decontextualized, for a categorical statement that "the death was a consequence of exposure to low temperature." The most established (and most scientifically correct, as could be upheld in court) practice remains, therefore, the collection and combination of as many morphological and biochemical results as possible, which can, when examined as a whole, corroborate, or not contradict, the sole/prevalent/contributing role that exposure to cold has had (or may have had) in the pathogenesis of the death (28)(29)(30). Postmortem morphological data, whether they be radiological (increased aerated lung percentage), macroscopic (frost erythema, Wischnewsky spots within the gastric mucosa), microscopic (Armanni-Ebstein kidney) or biochemical (increased urinary catecholamines and metanephrines, increased blood ketones, increased urinary and postmortem serum cortisol, increased free fatty acids in the postmortem serum), do not necessarily indicate with certainty that the death is the result of exposure to low temperatures, even if they may allow one to better direct the diagnosis, especially in cases for which there is suggestive circumstantial evidence, and in the absence of other causes of death (1,28,29,(31)(32)(33).…”

Analysis of Tryptophan Metabolites in Serum Using Wide-Isolation Strategies for UHPLC–HRMS/MS

“…Quantitation of small metabolites in biological samples via mass spectrometry (MS) using liquid chromatography (LC) has often been limited to the use of highly targeted or low-resolution methods solely for the purpose of exclusively quantifying key metabolites. − In complex systems, however, quantitation of a few metabolites alone cannot depict the broad picture of the biochemical interactions, as related compounds will be missed. For a more complete analysis, a global metabolomics approach is often adopted; however, this often requires a separate analysis from quantitative efforts due to the importance of preserving faster scan times on the mass analyzer while maintaining high specificity. , For this reason, performing MS/MS for the purpose of quantitation within a global analysis is not often performed using high-resolution instrumentation (HRMS) unless solely within single MS analysis − or highly limited tandem MS/MS to minimize intensive scanning times.…”

Applications of Metabolomics in Forensic Toxicology and Forensic Medicine

“…Although still developing in forensics, the metabolomics approach is already considered a helpful tool for various legal questions (e.g., estimation of the postmortem interval, PMI) [ 7 ]. Metabolomics techniques can also be useful for indicating novel biomarkers with better diagnostic performance than those already existing [ 8 ] or estimating mortality risk in global disease (e.g., acute myocardial infarction) [ 9 ]. Techniques of metabolomics and computational biology have also been used to build a quantitative forecast model for early warning of rapid death [ 10 ].…”