Preliminary Metabolomic Profiling of the Vitreous Humor from Hypothermia Fatalities

The
postmortem diagnosis of hypothermia fatalities is often complex
due to the absence of pathognomonic lesions and biomarkers. In this
study, potential novel biomarkers of hypothermia fatalities were searched
in the vitreous humor of known cases of hypothermia fatalities (n = 20) compared to control cases (n =
16), using a targeted metabolomics approach allowing quantitative
detection of 188 metabolites. A robust discriminant model with good
predictivity was obtained with the supervised OPLS-DA multivariate
analysis, showing a distinct separation between the hypothermia and
control groups. This signature was characterized by the decreased
concentrations of five metabolites (methionine sulfoxide, tryptophan,
phenylalanine, alanine, and ornithine) and the increased concentration
of 28 metabolites (21 phosphatidylcholines, 3 sphingomyelins, spermine,
citrulline, acetylcarnitine, and hydroxybutyrylcarnitine) in hypothermia
fatalities compared to controls. The signature shows similarities
with already identified features in serum such as the altered concentrations
of tryptophan, acylcarnitines, and unsaturated phosphatidylcholines,
revealing a highly significant increased activity of methionine sulfoxide
reductase, attested by a low methionine sulfoxide-to-methionine ratio.
Our results show a preliminary metabolomics signature of hypothermia
fatalities in the vitreous humor, highlighting an increased methionine
sulfoxide reductase activity.