Forensic metabolomics: Tracing cyanide-induced metabolic changes in fatalities

Abstract

Accurate detection of cyanide exposure is crucial, particularly in forensic science. However, cyanide's high volatility and potential biochemical conversions in biological samples pose challenges for direct detection, complicating the determination of cause of death. Identifying alternative cyanide metabolites as markers may mitigate false negatives and positives, extending the detection window in poisoning cases. This study aimed to evaluate metabolic changes induced by cyanide exposure in forensic cases using a multi-platform approach, including metabolomics and lipidomics analyses via liquid and gas chromatography coupled with high-resolution mass spectrometry. Results demonstrated clear discrimination between cyanide-exposed and control groups through OPLS-DA models. A total of 92 altered metabolites were identified in cyanide-exposed individuals compared to controls. Significant changes in metabolites primarily included glycerophospholipids (30.7 %), glycerolipids (14 %), fatty acyls (12.9 %), sphingolipids (8.0 %), amino acids and analogs (8.0 %), among others. Cyanide intoxication disrupted multiple metabolic pathways, including mitochondrial β-oxidation, acylcarnitine accumulation, a shift towards gluconeogenesis in amino acid metabolism, and ammonia homeostasis disturbance, affecting both ammonia recycling and the urea cycle. These pathways are essential for cellular energy production. The altered metabolic profiles provide insight into cyanide poisoning pathways, potentially aiding the development of new forensic diagnostic strategies. The area under the receiver operating characteristic curve was used to assess each model's predictive value. Findings suggest that metabolites such as phosphate and 3-hydroxybutyric acid could serve as diagnostic biomarkers in lethal cyanide poisoning cases. Future studies must evaluate these potential biomarkers' effectiveness in different fatal victim cohorts and validate the suggested panel through a targeted approach.

Keywords: Cyanide; Exposure biomarkers; Forensic toxicology; Untargeted metabolomics.