Elucidating of the metabolic impact of risperidone on brain microvascular endothelial cells using untargeted metabolomics-based LC-MS
Risperidone is useful for the treatment of schizophrenia symptoms; however, it also has side effects, and an overdose can be harmful. The metabolic effects of risperidone at high therapeutic doses and its metabolites have not been elucidated. Endogenous cellular metabolites may be comprehensively an...
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| Language: | English |
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Elsevier
2024-12-01
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| Series: | Toxicology Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S221475002400074X |
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| author | Surachai Ngamratanapaiboon Napatarin Srikornvit Patipol Hongthawonsiri Krittaboon Pornchokchai Siriphattarinya Wongpitoonmanachai Jiajun Mo Petchlada Pholkla Pracha Yambangyang Phichanan Duchda Jenyuk Lohwacharin Watcharaporn Devakul Na Ayutthaya |
| author_facet | Surachai Ngamratanapaiboon Napatarin Srikornvit Patipol Hongthawonsiri Krittaboon Pornchokchai Siriphattarinya Wongpitoonmanachai Jiajun Mo Petchlada Pholkla Pracha Yambangyang Phichanan Duchda Jenyuk Lohwacharin Watcharaporn Devakul Na Ayutthaya |
| author_sort | Surachai Ngamratanapaiboon |
| collection | DOAJ |
| description | Risperidone is useful for the treatment of schizophrenia symptoms; however, it also has side effects, and an overdose can be harmful. The metabolic effects of risperidone at high therapeutic doses and its metabolites have not been elucidated. Endogenous cellular metabolites may be comprehensively analyzed using untargeted metabolomics-based liquid chromatography-mass spectrometry (LC-MS), which can reveal changes in cell regulation and metabolic pathways. By identifying the metabolites and pathway changes using a nontargeted metabolomics-based LC-MS approach, we aimed to shed light on the potential toxicological effects of high-dose risperidone on brain microvascular endothelial cells (MVECs) associated with the human blood brain barrier. A total of 42 metabolites were selected as significant putative metabolites of the toxicological response of high-dose risperidone in MVECs. Six highly correlated pathways were identified, including those involving diacylglycerol, fatty acid, ceramide, glycerophospholipid, amino acid, and tricarboxylic acid metabolism. We demonstrated that methods focused on metabolomics are useful for identifying metabolites that may be used to clarify the mechanism of drug-induced toxicity. |
| format | Article |
| id | doaj-art-6201f2477e284e24b5706f0dc952d882 |
| institution | Kabale University |
| issn | 2214-7500 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Toxicology Reports |
| spelling | doaj-art-6201f2477e284e24b5706f0dc952d8822024-12-19T10:54:25ZengElsevierToxicology Reports2214-75002024-12-0113101691Elucidating of the metabolic impact of risperidone on brain microvascular endothelial cells using untargeted metabolomics-based LC-MSSurachai Ngamratanapaiboon0Napatarin Srikornvit1Patipol Hongthawonsiri2Krittaboon Pornchokchai3Siriphattarinya Wongpitoonmanachai4Jiajun Mo5Petchlada Pholkla6Pracha Yambangyang7Phichanan Duchda8Jenyuk Lohwacharin9Watcharaporn Devakul Na Ayutthaya10Division of Pharmacology, Department of Basic Medical Sciences, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Dusit, Bangkok 10300, Thailand; Corresponding author.Medical Student in Doctor of Medicine Programme, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Dusit, Bangkok 10300, ThailandMedical Student in Doctor of Medicine Programme, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Dusit, Bangkok 10300, ThailandMedical Student in Doctor of Medicine Programme, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Dusit, Bangkok 10300, ThailandMedical Student in Doctor of Medicine Programme, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Dusit, Bangkok 10300, ThailandMedical Student in Doctor of Medicine Programme, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Dusit, Bangkok 10300, ThailandMedical Student in Doctor of Medicine Programme, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Dusit, Bangkok 10300, ThailandDepartment of Biomedical Engineering, Faculty of Engineering, Mahidol University, Salaya, Nakhon Pathom 73170, ThailandDepartment of Environmental Engineering, Faculty of Engineering, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand; Professor Aroon Sorathesn Center of Excellence in Environmental Engineering, Department of Environmental Engineering, Faculty of Engineering, Chulalongkorn University, Bangkok, 10330, ThailandDepartment of Environmental Engineering, Faculty of Engineering, Chulalongkorn University, Pathumwan, Bangkok 10330, Thailand; Professor Aroon Sorathesn Center of Excellence in Environmental Engineering, Department of Environmental Engineering, Faculty of Engineering, Chulalongkorn University, Bangkok, 10330, ThailandDivision of Pharmacology, Department of Basic Medical Sciences, Faculty of Medicine Vajira Hospital, Navamindradhiraj University, Dusit, Bangkok 10300, ThailandRisperidone is useful for the treatment of schizophrenia symptoms; however, it also has side effects, and an overdose can be harmful. The metabolic effects of risperidone at high therapeutic doses and its metabolites have not been elucidated. Endogenous cellular metabolites may be comprehensively analyzed using untargeted metabolomics-based liquid chromatography-mass spectrometry (LC-MS), which can reveal changes in cell regulation and metabolic pathways. By identifying the metabolites and pathway changes using a nontargeted metabolomics-based LC-MS approach, we aimed to shed light on the potential toxicological effects of high-dose risperidone on brain microvascular endothelial cells (MVECs) associated with the human blood brain barrier. A total of 42 metabolites were selected as significant putative metabolites of the toxicological response of high-dose risperidone in MVECs. Six highly correlated pathways were identified, including those involving diacylglycerol, fatty acid, ceramide, glycerophospholipid, amino acid, and tricarboxylic acid metabolism. We demonstrated that methods focused on metabolomics are useful for identifying metabolites that may be used to clarify the mechanism of drug-induced toxicity.http://www.sciencedirect.com/science/article/pii/S221475002400074XUntargeted metabolomicsLiquid chromatography-mass spectrometryBrain microvascular endothelial cellsRisperidone |
| spellingShingle | Surachai Ngamratanapaiboon Napatarin Srikornvit Patipol Hongthawonsiri Krittaboon Pornchokchai Siriphattarinya Wongpitoonmanachai Jiajun Mo Petchlada Pholkla Pracha Yambangyang Phichanan Duchda Jenyuk Lohwacharin Watcharaporn Devakul Na Ayutthaya Elucidating of the metabolic impact of risperidone on brain microvascular endothelial cells using untargeted metabolomics-based LC-MS Toxicology Reports Untargeted metabolomics Liquid chromatography-mass spectrometry Brain microvascular endothelial cells Risperidone |
| title | Elucidating of the metabolic impact of risperidone on brain microvascular endothelial cells using untargeted metabolomics-based LC-MS |
| title_full | Elucidating of the metabolic impact of risperidone on brain microvascular endothelial cells using untargeted metabolomics-based LC-MS |
| title_fullStr | Elucidating of the metabolic impact of risperidone on brain microvascular endothelial cells using untargeted metabolomics-based LC-MS |
| title_full_unstemmed | Elucidating of the metabolic impact of risperidone on brain microvascular endothelial cells using untargeted metabolomics-based LC-MS |
| title_short | Elucidating of the metabolic impact of risperidone on brain microvascular endothelial cells using untargeted metabolomics-based LC-MS |
| title_sort | elucidating of the metabolic impact of risperidone on brain microvascular endothelial cells using untargeted metabolomics based lc ms |
| topic | Untargeted metabolomics Liquid chromatography-mass spectrometry Brain microvascular endothelial cells Risperidone |
| url | http://www.sciencedirect.com/science/article/pii/S221475002400074X |
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