Metabolomics of post-mortem blood: identifying potential markers of post-mortem interval
- 662 Downloads
Death results in changes in some metabolites in body tissues due to lack of circulating oxygen, altered enzymatic reactions, cellular degradation, and cessation of anabolic production of metabolites and macromolecules. Metabolic changes may provide chemical markers to better determine the time since death (post-mortem interval), something that is challenging to establish with current observation-based methodologies. The aim of this research was to carry out a metabolic analysis of blood plasma post-mortem, in order to gain a more complete understanding of the biochemical changes that occur following death. Gas chromatography was used to conduct a survey of post-mortem rat blood. Sixty six metabolites were detected post-mortem. Twenty six of these [18 amino acids, glutathione (GSH), 4-Amino-n-butyric acid (GABA), glyoxylate, oxalate, hydroxyproline, creatinine, α-ketoglutarate and succinate] had increased concentrations post-mortem. The remaining 40 metabolites had concentrations that were not dependant on time. This study demonstrates the range of metabolic changes that occur post-mortem as well as identifying potential markers for estimating post-mortem interval.
KeywordsPost-mortem interval Biochemical markers Blood metabolites Hypoxia GC–MS Forensic science Amino acids
The authors wish to thank Dr. Stephen Cordiner, (ESR, Porirua) and Dr. Rachel Fleming (ESR, Mt Albert) for their kind suggestions and useful comments throughout the course of this study, Dr. Silas Villas-Boas, Margarita Markovskaya and Dung Nguyen from the University of Auckland for the assistance and technical support throughout the GC–MS analysis, and Dr. John Schofield, Lesley Schofield and Dave Matthews at the University of Otago, for the handling and euthanasia of the rats used in this study. Andrea Donaldson was supported by a Te Tipu Putaiao PhD Scholarship from The Ministry of Science and Innovation, Wellington, New Zealand.
Conflict of interest
Author Andrea Donaldson and author Iain Lamont declare that they have no conflict of interest with the organization that supported the research.
Informed consent statement
All institutional and national guidelines for the care and use of laboratory animals were followed. No human studies were carried out by the authors for this article.
- Clark, M. A., Worrell, M. B., & Pless, J. E. (1997). Postmortem changes in soft tissue. In W. D. Haglund & M. H. Sorg (Eds.), Forensic taphonomy: The postmortem fate of human remains (pp. 151–164). Florida: CRC Press.Google Scholar
- Comte, B., Vincent, G., Bouchard, B., Benderdour, M., & Des Rosiers, C. (2002). Reverse flux through cardiac NADP+-isocitrate dehydrogenase under normoxia and ischemia. American Journal of Physiology—Heart and Circulatory Physiology, 283(4), H1505–H1514. doi: 10.1152/ajpheart.00287.2002.PubMedGoogle Scholar
- Cotran, R. S., Kumar, V., & Robbins, S. L. (1994). Cellular injury and cellular death. In F. J. Schoen (Ed.), Robbins pathologic basis of disease (5th ed., pp. 4–11). Philadelphia: W.B. Saunders Company.Google Scholar
- Des Rosiers, C., Donato, L. D., Comte, B., et al. (1995). Isotopomer analysis of citric acid cycle and gluconeogenesis in rat liver: Reversibility of isocitrate dehydrogenase and involvement of ATP-citrate lyase in gluconeogenesis. Journal of Biological Chemistry, 270(17), 10027–10036.PubMedCrossRefGoogle Scholar
- Donaldson, A., & Lamont, I. (2013a). Estimation of post-mortem interval using biochemical markers. Australian Journal of Forensic Sciences. doi: 10.1080/00450618.2013.784356.
- Gill-King, H. (1997). Chemical and ultrastructural aspects of decompositions. In W. Haglund & M. Sorg (Eds.), Forensic taphonomy: The postmortem fate of human remains (pp. 93–105). Florida: CRC Press.Google Scholar
- Holmes, R. P., Knight, J., & Assimos, D. G.(2007) Origin of urinary oxalate. In A. P. Evan, J. E. Lingeman, & J. C. Williams Jr (Eds.), Renal Stone Disease. 1st annual international urolithiasis research symposium, Melville, NY: American Institute of Physics.Google Scholar
- Jetter, W., & McLean, R. (1943). Biochemical changes in body fluids after death. American Journal of Clinical Pathology, 13, 178–185.Google Scholar
- Micozzi, M. S. (1991). Postmortem changes in human and animal remains: A systematic approach. Springfield, IL: Charles C Thomas.Google Scholar
- Mullen, A., Wheaton, W., Jin, E., et al. (2012). Reductive carboxylation supports growth in tumour cells with defective mitochondria. Nature, 481, 385–388.Google Scholar
- Powers, R. H. (2005). The decomposition of human remains: A biochemical perspective. In J. Rich, D. E. Dean, & R. H. Powers (Eds.), Forensic medicine of the lower extremity: Human identification and trauma analysis of the thigh, leg, and foot (pp. 1–13). Totowa: The Humana Press Inc.Google Scholar
- Voet, D., & Voet, J. G. (2004). Biochemistry (3rd ed.). Hoboken: Wiley.Google Scholar