Spatiotemporal pharmacometabolomics based on ambient mass spectrometry imaging to evaluate the metabolism and hepatotoxicity of amiodarone in HepG2 spheroids
Three-dimensional (3D) cell spheroid models combined with mass spectrometry imaging (MSI) enables innovative investigation of in vivo-like biological processes under different physiological and pathological conditions. Herein, airflow-assisted desorption electrospray ionization-MSI (AFADESI-MSI) was...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Journal of Pharmaceutical Analysis |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2095177923000679 |
| _version_ | 1797812071050510336 |
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| author | Limei Li Qingce Zang Xinzhu Li Ying Zhu Shanjing Wen Jiuming He Ruiping Zhang Zeper Abliz |
| author_facet | Limei Li Qingce Zang Xinzhu Li Ying Zhu Shanjing Wen Jiuming He Ruiping Zhang Zeper Abliz |
| author_sort | Limei Li |
| collection | DOAJ |
| description | Three-dimensional (3D) cell spheroid models combined with mass spectrometry imaging (MSI) enables innovative investigation of in vivo-like biological processes under different physiological and pathological conditions. Herein, airflow-assisted desorption electrospray ionization-MSI (AFADESI-MSI) was coupled with 3D HepG2 spheroids to assess the metabolism and hepatotoxicity of amiodarone (AMI). High-coverage imaging of >1100 endogenous metabolites in hepatocyte spheroids was achieved using AFADESI-MSI. Following AMI treatment at different times, 15 metabolites of AMI involved in N-desethylation, hydroxylation, deiodination, and desaturation metabolic reactions were identified, and according to their spatiotemporal dynamics features, the metabolic pathways of AMI were proposed. Subsequently, the temporal and spatial changes in metabolic disturbance within spheroids caused by drug exposure were obtained via metabolomic analysis. The main dysregulated metabolic pathways included arachidonic acid and glycerophospholipid metabolism, providing considerable evidence for the mechanism of AMI hepatotoxicity. In addition, a biomarker group of eight fatty acids was selected that provided improved indication of cell viability and could characterize the hepatotoxicity of AMI. The combination of AFADESI-MSI and HepG2 spheroids can simultaneously obtain spatiotemporal information for drugs, drug metabolites, and endogenous metabolites after AMI treatment, providing an effective tool for in vitro drug hepatotoxicity evaluation. |
| first_indexed | 2024-03-13T07:32:08Z |
| format | Article |
| id | doaj.art-09d5850106504762a8d26554380abb47 |
| institution | Directory Open Access Journal |
| issn | 2095-1779 |
| language | English |
| last_indexed | 2024-03-13T07:32:08Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmaceutical Analysis |
| spelling | doaj.art-09d5850106504762a8d26554380abb472023-06-04T04:23:39ZengElsevierJournal of Pharmaceutical Analysis2095-17792023-05-01135483493Spatiotemporal pharmacometabolomics based on ambient mass spectrometry imaging to evaluate the metabolism and hepatotoxicity of amiodarone in HepG2 spheroidsLimei Li0Qingce Zang1Xinzhu Li2Ying Zhu3Shanjing Wen4Jiuming He5Ruiping Zhang6Zeper Abliz7State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, ChinaState Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China; Corresponding author.State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China; Key Laboratory of Mass Spectrometry Imaging and Metabolomics (Minzu University of China), National Ethnic Affairs Commission, Beijing, 100081, China; Center for Imaging and Systems Biology, College of Life and Environmental Sciences, Minzu University of China, Beijing, 100081, China; Corresponding author. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.Three-dimensional (3D) cell spheroid models combined with mass spectrometry imaging (MSI) enables innovative investigation of in vivo-like biological processes under different physiological and pathological conditions. Herein, airflow-assisted desorption electrospray ionization-MSI (AFADESI-MSI) was coupled with 3D HepG2 spheroids to assess the metabolism and hepatotoxicity of amiodarone (AMI). High-coverage imaging of >1100 endogenous metabolites in hepatocyte spheroids was achieved using AFADESI-MSI. Following AMI treatment at different times, 15 metabolites of AMI involved in N-desethylation, hydroxylation, deiodination, and desaturation metabolic reactions were identified, and according to their spatiotemporal dynamics features, the metabolic pathways of AMI were proposed. Subsequently, the temporal and spatial changes in metabolic disturbance within spheroids caused by drug exposure were obtained via metabolomic analysis. The main dysregulated metabolic pathways included arachidonic acid and glycerophospholipid metabolism, providing considerable evidence for the mechanism of AMI hepatotoxicity. In addition, a biomarker group of eight fatty acids was selected that provided improved indication of cell viability and could characterize the hepatotoxicity of AMI. The combination of AFADESI-MSI and HepG2 spheroids can simultaneously obtain spatiotemporal information for drugs, drug metabolites, and endogenous metabolites after AMI treatment, providing an effective tool for in vitro drug hepatotoxicity evaluation.http://www.sciencedirect.com/science/article/pii/S2095177923000679Mass spectrometry imagingHepG2 spheroidsHepatotoxicityDrug metabolismAmiodarone |
| spellingShingle | Limei Li Qingce Zang Xinzhu Li Ying Zhu Shanjing Wen Jiuming He Ruiping Zhang Zeper Abliz Spatiotemporal pharmacometabolomics based on ambient mass spectrometry imaging to evaluate the metabolism and hepatotoxicity of amiodarone in HepG2 spheroids Journal of Pharmaceutical Analysis Mass spectrometry imaging HepG2 spheroids Hepatotoxicity Drug metabolism Amiodarone |
| title | Spatiotemporal pharmacometabolomics based on ambient mass spectrometry imaging to evaluate the metabolism and hepatotoxicity of amiodarone in HepG2 spheroids |
| title_full | Spatiotemporal pharmacometabolomics based on ambient mass spectrometry imaging to evaluate the metabolism and hepatotoxicity of amiodarone in HepG2 spheroids |
| title_fullStr | Spatiotemporal pharmacometabolomics based on ambient mass spectrometry imaging to evaluate the metabolism and hepatotoxicity of amiodarone in HepG2 spheroids |
| title_full_unstemmed | Spatiotemporal pharmacometabolomics based on ambient mass spectrometry imaging to evaluate the metabolism and hepatotoxicity of amiodarone in HepG2 spheroids |
| title_short | Spatiotemporal pharmacometabolomics based on ambient mass spectrometry imaging to evaluate the metabolism and hepatotoxicity of amiodarone in HepG2 spheroids |
| title_sort | spatiotemporal pharmacometabolomics based on ambient mass spectrometry imaging to evaluate the metabolism and hepatotoxicity of amiodarone in hepg2 spheroids |
| topic | Mass spectrometry imaging HepG2 spheroids Hepatotoxicity Drug metabolism Amiodarone |
| url | http://www.sciencedirect.com/science/article/pii/S2095177923000679 |
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