Dynamic Changes in Plasma Metabolic Profiles Reveal a Potential Metabolite Panel for Interpretation of Fatal Intoxication by Chlorpromazine or Olanzapine in Mice

Rui Bai; Xiaohui Dai; Xingang Miao; Bing Xie; Feng Yu; Bin Cong; Di Wen; Chunling Ma

doi:10.3390/metabo12121184

Metabolites (Nov 2022)

Dynamic Changes in Plasma Metabolic Profiles Reveal a Potential Metabolite Panel for Interpretation of Fatal Intoxication by Chlorpromazine or Olanzapine in Mice

Rui Bai,
Xiaohui Dai,
Xingang Miao,
Bing Xie,
Feng Yu,
Bin Cong,
Di Wen,
Chunling Ma

Affiliations

Rui Bai: Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, China
Xiaohui Dai: Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, China
Xingang Miao: Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, China
Bing Xie: Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, China
Feng Yu: Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, China
Bin Cong: Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, China
Di Wen: Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, China
Chunling Ma: Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, College of Forensic Medicine, Hebei Medical University, Shijiazhuang 050017, China

DOI: https://doi.org/10.3390/metabo12121184
Journal volume & issue: Vol. 12, no. 12
p. 1184

Abstract

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Diagnosing the cause of fatal intoxication by antipsychotic agents is an important task in forensic practice. In the 2020 Annual Report of the American Association of Poison Control Centers, among 40 deaths caused by antipsychotics, 21 cases were diagnosed as “probably responsible”, thereby indicating that more objective diagnostic tools are needed. We used liquid chromatography-mass spectrometry-based integrated metabolomics analysis to measure changes in metabolic profiles in the plasma of mice that died from fatal intoxication due to chlorpromazine (CPZ) or olanzapine (OLA). These results were used to construct a stable discriminative classification model (DCM) comprising L-acetylcarnitine, succinic acid, and propionylcarnitine between fatal intoxication caused by CPZ/OLA and cervical dislocation (control). Performance evaluation of the classification model in mice that suffered fatal intoxication showed relative specificity for different pharmacodynamic drugs and relative sensitivity in different life states (normal, intoxication, fatal intoxication). A stable level of L-acetylcarnitine and variable levels of succinic acid and propionylcarnitine between fatal-intoxication and intoxication groups revealed procedural perturbations in metabolic pathways related to fatal intoxication by CPZ/OLA. Additional stability studies revealed that decomposition of succinic acid in fatal-intoxication samples (especially in the OLA group) could weaken the prediction performance of the binary-classification model; however, levels of these three potential metabolites measured within 6 days in fresh samples kept at 4 °C revealed a good performance of our model. Our findings suggest that metabolomics analysis can be used to explore metabolic alterations during fatal intoxication due to use of antipsychotic agents and provide evidence for the cause of death.

Published in Metabolites

ISSN: 2218-1989 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Microbiology
Website: http://www.mdpi.com/journal/metabolites

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