Cargando…

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

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 indicati...

Descripción completa

Detalles Bibliográficos
Autores principales: Bai, Rui, Dai, Xiaohui, Miao, Xingang, Xie, Bing, Yu, Feng, Cong, Bin, Wen, Di, Ma, Chunling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9782175/
https://www.ncbi.nlm.nih.gov/pubmed/36557223
http://dx.doi.org/10.3390/metabo12121184
_version_ 1784857278635048960
author Bai, Rui
Dai, Xiaohui
Miao, Xingang
Xie, Bing
Yu, Feng
Cong, Bin
Wen, Di
Ma, Chunling
author_facet Bai, Rui
Dai, Xiaohui
Miao, Xingang
Xie, Bing
Yu, Feng
Cong, Bin
Wen, Di
Ma, Chunling
author_sort Bai, Rui
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9782175
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-97821752022-12-24 Dynamic Changes in Plasma Metabolic Profiles Reveal a Potential Metabolite Panel for Interpretation of Fatal Intoxication by Chlorpromazine or Olanzapine in Mice Bai, Rui Dai, Xiaohui Miao, Xingang Xie, Bing Yu, Feng Cong, Bin Wen, Di Ma, Chunling Metabolites Article 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. MDPI 2022-11-27 /pmc/articles/PMC9782175/ /pubmed/36557223 http://dx.doi.org/10.3390/metabo12121184 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bai, Rui
Dai, Xiaohui
Miao, Xingang
Xie, Bing
Yu, Feng
Cong, Bin
Wen, Di
Ma, Chunling
Dynamic Changes in Plasma Metabolic Profiles Reveal a Potential Metabolite Panel for Interpretation of Fatal Intoxication by Chlorpromazine or Olanzapine in Mice
title Dynamic Changes in Plasma Metabolic Profiles Reveal a Potential Metabolite Panel for Interpretation of Fatal Intoxication by Chlorpromazine or Olanzapine in Mice
title_full Dynamic Changes in Plasma Metabolic Profiles Reveal a Potential Metabolite Panel for Interpretation of Fatal Intoxication by Chlorpromazine or Olanzapine in Mice
title_fullStr Dynamic Changes in Plasma Metabolic Profiles Reveal a Potential Metabolite Panel for Interpretation of Fatal Intoxication by Chlorpromazine or Olanzapine in Mice
title_full_unstemmed Dynamic Changes in Plasma Metabolic Profiles Reveal a Potential Metabolite Panel for Interpretation of Fatal Intoxication by Chlorpromazine or Olanzapine in Mice
title_short Dynamic Changes in Plasma Metabolic Profiles Reveal a Potential Metabolite Panel for Interpretation of Fatal Intoxication by Chlorpromazine or Olanzapine in Mice
title_sort dynamic changes in plasma metabolic profiles reveal a potential metabolite panel for interpretation of fatal intoxication by chlorpromazine or olanzapine in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9782175/
https://www.ncbi.nlm.nih.gov/pubmed/36557223
http://dx.doi.org/10.3390/metabo12121184
work_keys_str_mv AT bairui dynamicchangesinplasmametabolicprofilesrevealapotentialmetabolitepanelforinterpretationoffatalintoxicationbychlorpromazineorolanzapineinmice
AT daixiaohui dynamicchangesinplasmametabolicprofilesrevealapotentialmetabolitepanelforinterpretationoffatalintoxicationbychlorpromazineorolanzapineinmice
AT miaoxingang dynamicchangesinplasmametabolicprofilesrevealapotentialmetabolitepanelforinterpretationoffatalintoxicationbychlorpromazineorolanzapineinmice
AT xiebing dynamicchangesinplasmametabolicprofilesrevealapotentialmetabolitepanelforinterpretationoffatalintoxicationbychlorpromazineorolanzapineinmice
AT yufeng dynamicchangesinplasmametabolicprofilesrevealapotentialmetabolitepanelforinterpretationoffatalintoxicationbychlorpromazineorolanzapineinmice
AT congbin dynamicchangesinplasmametabolicprofilesrevealapotentialmetabolitepanelforinterpretationoffatalintoxicationbychlorpromazineorolanzapineinmice
AT wendi dynamicchangesinplasmametabolicprofilesrevealapotentialmetabolitepanelforinterpretationoffatalintoxicationbychlorpromazineorolanzapineinmice
AT machunling dynamicchangesinplasmametabolicprofilesrevealapotentialmetabolitepanelforinterpretationoffatalintoxicationbychlorpromazineorolanzapineinmice