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1
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Hua Y, Wang R, Liu Y, Liu Q, Qi X, Ding Y, Lv J. Metabolomics analysis reveals characteristic metabolites in different levels of oxaliplatin-induced neurotoxicity. J Sep Sci 2024; 47:e2400164. [PMID: 38819794 DOI: 10.1002/jssc.202400164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Revised: 04/30/2024] [Accepted: 05/05/2024] [Indexed: 06/01/2024]
Abstract
Oxaliplatin (L-OHP), a third-generation platinum-based anti-tumor drug, finds widespread application in the first-line treatment of metastatic colorectal cancer. Despite its efficacy, the drug's usage is curtailed by a litany of side effects, with L-OHP-induced peripheral neuropathy (OIPN) being the most debilitating. This condition can be classified into varying degrees of severity. Employing serum metabolomics, a high-sensitivity, high-throughput technique, holds promise as a method to identify biomarkers for clinical assessment and monitoring of OIPN patients across different severity levels. In our study, we analyzed serum metabolites in patients with different OIPN levels using ultra-performance liquid chromatography-high resolution mass spectrometry. By employing statistical analyses and pathway enrichment studies, we aimed to identify potential biomarkers and metabolic pathways. Our findings characterized the serum metabolic profiles of patients with varying OIPN levels. Notably, pathway analysis revealed a significant correlation with lipid metabolism, amino acid metabolism, and energy metabolism. Multivariate statistical analysis and receiver operator characteristic curve evaluation pointed to anhalamine and glycochenodeoxycholic acid as potential biomarkers for OIPN C and A, which suggest that serum metabolomics may serve as a potent tool for exploring the metabolic status of patients suffering from diverse diseases and for discovering novel biomarkers.
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Affiliation(s)
- Yujiao Hua
- Department of Clinical Pharmacy, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Rong Wang
- Department of Pathology, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Yankui Liu
- Department of Pathology, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Quan Liu
- Medical Oncology Three, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Xiaowei Qi
- Department of Pathology, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Yongjuan Ding
- Department of Clinical Pharmacy, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Juan Lv
- Department of Clinical Pharmacy, Affiliated Hospital of Jiangnan University, Wuxi, China
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2
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Fu J, Zhu F, Xu CJ, Li Y. Metabolomics meets systems immunology. EMBO Rep 2023; 24:e55747. [PMID: 36916532 PMCID: PMC10074123 DOI: 10.15252/embr.202255747] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Revised: 12/24/2022] [Accepted: 02/24/2023] [Indexed: 03/16/2023] Open
Abstract
Metabolic processes play a critical role in immune regulation. Metabolomics is the systematic analysis of small molecules (metabolites) in organisms or biological samples, providing an opportunity to comprehensively study interactions between metabolism and immunity in physiology and disease. Integrating metabolomics into systems immunology allows the exploration of the interactions of multilayered features in the biological system and the molecular regulatory mechanism of these features. Here, we provide an overview on recent technological developments of metabolomic applications in immunological research. To begin, two widely used metabolomics approaches are compared: targeted and untargeted metabolomics. Then, we provide a comprehensive overview of the analysis workflow and the computational tools available, including sample preparation, raw spectra data preprocessing, data processing, statistical analysis, and interpretation. Third, we describe how to integrate metabolomics with other omics approaches in immunological studies using available tools. Finally, we discuss new developments in metabolomics and its prospects for immunology research. This review provides guidance to researchers using metabolomics and multiomics in immunity research, thus facilitating the application of systems immunology to disease research.
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Affiliation(s)
- Jianbo Fu
- Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.,TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.,College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
| | - Feng Zhu
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China
| | - Cheng-Jian Xu
- Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.,TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.,Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Yang Li
- Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.,TWINCORE Centre for Experimental and Clinical Infection Research, a joint venture between the Helmholtz Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.,Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands
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3
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Martin-Grau M, Marrachelli VG, Monleon D. Rodent models and metabolomics in non-alcoholic fatty liver disease: What can we learn? World J Hepatol 2022; 14:304-318. [PMID: 35317178 PMCID: PMC8891675 DOI: 10.4254/wjh.v14.i2.304] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 04/13/2021] [Accepted: 01/29/2022] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) prevalence has increased drastically in recent decades, affecting up to 25% of the world’s population. NAFLD is a spectrum of different diseases that starts with asymptomatic steatosis and continues with development of an inflammatory response called steatohepatitis, which can progress to fibrosis. Several molecular and metabolic changes are required for the hepatocyte to finally vary its function; hence a “multiple hit” hypothesis seems a more accurate proposal. Previous studies and current knowledge suggest that in most cases, NAFLD initiates and progresses through most of nine hallmarks of the disease, although the triggers and mechanisms for these can vary widely. The use of animal models remains crucial for understanding the disease and for developing tools based on biological knowledge. Among certain requirements to be met, a good model must imitate certain aspects of the human NAFLD disorder, be reliable and reproducible, have low mortality, and be compatible with a simple and feasible method. Metabolism studies in these models provides a direct reflection of the workings of the cell and may be a useful approach to better understand the initiation and progression of the disease. Metabolomics seems a valid tool for studying metabolic pathways and crosstalk between organs affected in animal models of NAFLD and for the discovery and validation of relevant biomarkers with biological understanding. In this review, we provide a brief introduction to NAFLD hallmarks, the five groups of animal models available for studying NAFLD and the potential role of metabolomics in the study of experimental NAFLD.
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Affiliation(s)
- Maria Martin-Grau
- Department of Pathology, University of Valencia, Valencia 46010, Spain
| | - Vannina G Marrachelli
- Department of Physiology, University of Valencia, Valencia 46010, Spain
- Health Research Institute INCLIVA, Valencia 46010, Spain
| | - Daniel Monleon
- Department of Pathology, University of Valencia, Valencia 46010, Spain
- Health Research Institute INCLIVA, Valencia 46010, Spain
- CIBER de Fragilidad y Envejecimiento Saludable (CIBERfes), Madrid 28029, Spain
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4
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Effects of ergotamine on the central nervous system using untargeted metabolomics analysis in a mouse model. Sci Rep 2021; 11:19542. [PMID: 34599239 PMCID: PMC8486802 DOI: 10.1038/s41598-021-98870-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Accepted: 09/15/2021] [Indexed: 01/02/2023] Open
Abstract
The ergot alkaloid ergotamine is produced by Claviceps purpurea, a parasitic fungus that commonly infects crops and pastures of high agricultural and economic importance. In humans and livestock, symptoms of ergotism include necrosis and gangrene, high blood pressure, heart rate, thermoregulatory dysfunction and hallucinations. However, ergotamine is also used in pharmaceutical applications to treat migraines and stop post-partum hemorrhage. To define its effects, metabolomic profiling of the brain was undertaken to determine pathways perturbed by ergotamine treatment. Metabolomic profiling identified the brainstem and cerebral cortex as regions with greatest variation. In the brainstem, dysregulation of the neurotransmitter epinephrine, and the psychoactive compound 2-arachidonylglycerol was identified. In the cerebral cortex, energy related metabolites isobutyryl-L-carnitine and S-3-oxodecanoyl cysteamine were affected and concentrations of adenylosuccinate, a metabolite associated with mental retardation, were higher. This study demonstrates, for the first time, key metabolomic pathways involved in the behavioural and physiological dysfunction of ergot alkaloid intoxicated animals.
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Li S, Wang Y, Li C, Yang N, Yu H, Zhou W, Chen S, Yang S, Li Y. Study on Hepatotoxicity of Rhubarb Based on Metabolomics and Network Pharmacology. DRUG DESIGN DEVELOPMENT AND THERAPY 2021; 15:1883-1902. [PMID: 33976539 PMCID: PMC8106470 DOI: 10.2147/dddt.s301417] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Accepted: 04/13/2021] [Indexed: 12/12/2022]
Abstract
Background Rhubarb, as a traditional Chinese medicine, is the preferred drug for the treatment of stagnation and constipation in clinical practice. It has been reported that rhubarb possesses hepatotoxicity, but its mechanism in vivo is still unclear. Methods In this study, the chemical components in rhubarb were identified based on UPLC-Q-TOF/MS combined with data postprocessing technology. The metabolic biomarkers obtained through metabolomics technology were related to rhubarb-induced hepatotoxicity. Furthermore, the potential targets of rhubarb-induced hepatotoxicity were obtained by network pharmacology involving the above components and metabolites. Meanwhile, GO gene enrichment analysis and KEGG pathway analysis were performed on the common targets. Results Twenty-eight components in rhubarb were identified based on UPLC-Q-TOF/MS, and 242 targets related to rhubarb ingredients were predicted. Nine metabolic biomarkers obtained through metabolomics technology were closely related to rhubarb-induced hepatotoxicity, and 282 targets of metabolites were predicted. Among them, the levels of 4 metabolites, namely dynorphin B (10–13), cervonoyl ethanolamide, lysoPE (18:2), and 3-hydroxyphenyl 2-hydroxybenzoate, significantly increased, while the levels of 5 metabolites, namely dopamine, biopterin, choline, coenzyme Q9 and P1, P4-bis (5ʹ-uridyl) tetraphosphate significantly decreased. In addition, 166 potential targets of rhubarb-induced hepatotoxicity were obtained by network pharmacology. The KEGG pathway analysis was performed on the common targets to obtain 46 associated signaling pathways. Conclusion These data suggested that rhubarb may cause liver toxicity due to its action on dopamine D1 receptor (DRD1), dopamine D2 receptor (DRD2), phosphodiesterase 4B (PDE4B), vanilloid receptor (TRPV1); transient receptor potential cation channel subfamily M member 8 (TRPM8), prostanoid EP2 receptor (PTGER2), acetylcholinesterase (ACHE), muscarinic acetylcholine receptor M3 (CHRM3) through the cAMP signaling pathway, cholinergic synapses, and inflammatory mediators to regulate TRP channels. Metabolomics technology and network pharmacology were integrated to explore rhubarb hepatotoxicity to promote the reasonable clinical application of rhubarb.
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Affiliation(s)
- Shanze Li
- Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China
| | - Yuming Wang
- Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China
| | - Chunyan Li
- Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China
| | - Na Yang
- Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China
| | - Hongxin Yu
- Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China
| | - Wenjie Zhou
- Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China
| | - Siyu Chen
- Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China
| | - Shenshen Yang
- Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China
| | - Yubo Li
- Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China
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Fu J, Zhang Y, Liu J, Lian X, Tang J, Zhu F. Pharmacometabonomics: data processing and statistical analysis. Brief Bioinform 2021; 22:6236068. [PMID: 33866355 DOI: 10.1093/bib/bbab138] [Citation(s) in RCA: 47] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2021] [Revised: 02/09/2021] [Accepted: 03/23/2021] [Indexed: 12/14/2022] Open
Abstract
Individual variations in drug efficacy, side effects and adverse drug reactions are still challenging that cannot be ignored in drug research and development. The aim of pharmacometabonomics is to better understand the pharmacokinetic properties of drugs and monitor the drug effects on specific metabolic pathways. Here, we systematically reviewed the recent technological advances in pharmacometabonomics for better understanding the pathophysiological mechanisms of diseases as well as the metabolic effects of drugs on bodies. First, the advantages and disadvantages of all mainstream analytical techniques were compared. Second, many data processing strategies including filtering, missing value imputation, quality control-based correction, transformation, normalization together with the methods implemented in each step were discussed. Third, various feature selection and feature extraction algorithms commonly applied in pharmacometabonomics were described. Finally, the databases that facilitate current pharmacometabonomics were collected and discussed. All in all, this review provided guidance for researchers engaged in pharmacometabonomics and metabolomics, and it would promote the wide application of metabolomics in drug research and personalized medicine.
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Affiliation(s)
- Jianbo Fu
- College of Pharmaceutical Sciences in Zhejiang University, China
| | - Ying Zhang
- College of Pharmaceutical Sciences in Zhejiang University, China
| | - Jin Liu
- College of Pharmaceutical Sciences in Zhejiang University, China
| | - Xichen Lian
- College of Pharmaceutical Sciences in Zhejiang University, China
| | - Jing Tang
- Department of Bioinformatics in Chongqing Medical University, China
| | - Feng Zhu
- College of Pharmaceutical Sciences in Zhejiang University, China
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7
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Deng Y, Yao H, Chen W, Wei H, Li X, Zhang F, Gao S, Man H, Chen J, Tao X, Li M, Chen W. Profiling of polar urine metabolite extracts from Chinese colorectal cancer patients to screen for potential diagnostic and adverse-effect biomarkers. J Cancer 2020; 11:6925-6938. [PMID: 33123283 PMCID: PMC7592006 DOI: 10.7150/jca.47631] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Accepted: 08/27/2020] [Indexed: 02/07/2023] Open
Abstract
Background: Metabolomics has demonstrated its potential in the early diagnosis, drug safety evaluation and personalized toxicology research of various cancers. Objectives: We aim to screen for potential diagnostic and capecitabine-related adverse effect (CRAE) biomarkers from urinary endogenous metabolites in Chinese colorectal cancer (CRC) patients. Methods: The metabolic profiles of 139 CRC patients and 50 non-neoplastic controls were analyzed using ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry. Results: There were 41 metabolites identified between the CRC patients and the non-neoplastic controls, and 19 metabolites were identified between CRC patients with and without CRAE. Based on these identified metabolites, bioinformatic analysis and prediction model construction were completed. Most of these differential metabolites have important roles in cell proliferation and differentiation and the immune system. Based on binary logistic regression, a CRC prediction model, composed of 3-methylhistidine, N-heptanoylglycine, N1,N12-diacetylspermine and hippurate, was established, with an area under curve (AUC) of 0.980 (95% CI: 0.953-1.000; sensitivity: 94.3%; specificity: 92.0%) in the training set, and an AUC of 0.968 (95% CI: 0.933-1.000; sensitivity: 89.9%; specificity: 92.0%) in the testing set. In addition, methionine and 4-pyridoxic acid can be combined to predict hand foot syndrome, with an AUC of 0.884; ubiquinone-1 and 4-pyridoxic acid can be combined to predict anemia, with an AUC of 0.889; and 5-acetamidovalerate and 3,4-methylenesebacic acid can be combined to predict neutropenia, with an AUC of 0.882. Conclusion: The profiling of urine polar metabolites has great potential in the early detection of CRC and the prediction of CRAE.
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Affiliation(s)
- Yi Deng
- Department of Pharmacy, Changzheng Hospital, Secondary Military Medical University, Shanghai, China, 200003
| | - Houshan Yao
- Department of Surgery, Changzheng Hospital, Secondary Military Medical University, Shanghai, China, 200003
| | - Wei Chen
- Department of Pharmacy, Changzheng Hospital, Secondary Military Medical University, Shanghai, China, 200003
| | - Hua Wei
- Department of Pharmacy, Changzheng Hospital, Secondary Military Medical University, Shanghai, China, 200003
| | - Xinxing Li
- Department of Surgery, Changzheng Hospital, Secondary Military Medical University, Shanghai, China, 200003
| | - Feng Zhang
- Department of Pharmacy, Changzheng Hospital, Secondary Military Medical University, Shanghai, China, 200003
| | - Shouhong Gao
- Department of Pharmacy, Changzheng Hospital, Secondary Military Medical University, Shanghai, China, 200003
| | - Huan Man
- Department of Pharmacy, Changzheng Hospital, Secondary Military Medical University, Shanghai, China, 200003
- College of Chemical and Biological Engineering, Yichun University, Jiangxi Province, China, 336000
| | - Jing Chen
- Department of Pharmacy, Changzheng Hospital, Secondary Military Medical University, Shanghai, China, 200003
- College of Chemical and Biological Engineering, Yichun University, Jiangxi Province, China, 336000
| | - Xia Tao
- Department of Pharmacy, Changzheng Hospital, Secondary Military Medical University, Shanghai, China, 200003
| | - Mingming Li
- Department of Pharmacy, Changzheng Hospital, Secondary Military Medical University, Shanghai, China, 200003
| | - Wansheng Chen
- Department of Pharmacy, Changzheng Hospital, Secondary Military Medical University, Shanghai, China, 200003
- Research and Development Center of Chinese Medicine Resources and Biotechnology, Shanghai University of Traditional Chinese Medicine, Shanghai, China, 201203
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8
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Sun L, Zhao M, Zhao Y, Wang M, Man J, Zhao C. Investigation of the therapeutic effect of Shaoyao Gancao decoction on CCL 4 -induced liver injury in rats by metabolomic analysis. Biomed Chromatogr 2020; 34:e4940. [PMID: 32634249 DOI: 10.1002/bmc.4940] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2020] [Revised: 06/21/2020] [Accepted: 06/30/2020] [Indexed: 12/13/2022]
Abstract
Shaoyao Gancao decoction (SGD) is a famous Chinese traditional prescription for treating liver injury. In this research, we investigated the therapeutic effects of SGD on liver injury and its metabolic mechanisms using 1 H NMR and UPLC-MS. Serum biochemical indicators and histopathological methods were used to determine the mechanism of action of SGD in treating liver injury. An orthogonal partial least squares discriminant analysis method was used to screen potential metabolic markers, and the MetaboAnalyst and KEGG PATHWAY databases were used to find relevant metabolic pathways. A total of 26 significant metabolites were identified with significant changes in their abundance levels, and these metabolites are involved in many metabolic pathways such as amino acid and lipid metabolism. The changes in biomarker levels reveal the therapeutic effect of SGD on liver injury, which is of great significance to speculate on possible metabolic mechanisms.
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Affiliation(s)
- Lin Sun
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China
| | - Min Zhao
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China
| | - Yanhui Zhao
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China
| | - Miao Wang
- School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
| | - Jingyi Man
- School of Business Administration, Shenyang Pharmaceutical University, Shenyang, China
| | - Chunjie Zhao
- School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China
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Liu C, Zhang C, He T, Sun L, Wang Q, Han S, Wang W, Kong J, Yuan F, Huang J. Study on potential toxic material base and mechanisms of hepatotoxicity induced by Dysosma versipellis based on toxicological evidence chain (TEC) concept. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2020; 190:110073. [PMID: 31851898 DOI: 10.1016/j.ecoenv.2019.110073] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/13/2019] [Revised: 12/03/2019] [Accepted: 12/07/2019] [Indexed: 06/10/2023]
Abstract
Dysosma Versipellis (DV), a traditional Chinese medicine, has the functions of eliminating phlegm, detoxification, dispersing knots . However, its serious toxicity limits its further use. Therefore, it is necessary to conduct a comprehensive toxicity study of DV, screen the basis of potential toxic substances and understand its toxic mechanism. Based on the concept of toxicological evidence chain (TEC), this study utilizes the technologies and means of chemomics, metabolomics, molecular docking and network toxicology flexibly, step by step to find the evidence of potential toxic components in the development of hepatotoxicity induced by DV, evidence of critical toxicity events, evidence of adverse outcomes, thus, a chain of toxicity evidence with reference and directivity can be organized. It further confirmed the toxic damage and potential molecular mechanism of DV. 5 potential toxic components were identified, namely, Podophyllotoxin-4-O-D-glucoside, Podorhizol, Podophyllotoxin, Podophyllotoxone and 3',4'-O,O-Didemethylpophyllotoxin. These chemical constituents affect phenylalanine metabolism, glycerophospholipid metabolism, energy metabolism and other related pathways by regulating PAH, SOD1, SOD2 and other related targets, then it induces oxidative stress, cell apoptosis, inflammatory reaction and energy consumption, which ultimately induces the occurrence of liver injury. The results of this study provide some reference for the follow-up analysis of toxicity mechanism of DV.
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Affiliation(s)
- Chuanxin Liu
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing, 102488, China
| | - Chenning Zhang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing, 102488, China; Institute of Wudang Traditional Chinese Medicine, Taihe Hospital, Hubei University of Medicine, Remmin South Road 32, Shiyan City, Hubei Province, 442000, China
| | - Tao He
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing, 102488, China
| | - Lu Sun
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing, 102488, China
| | - Qiang Wang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing, 102488, China
| | - Shuang Han
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing, 102488, China
| | - Wenxin Wang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing, 102488, China
| | - Jiao Kong
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing, 102488, China
| | - Fuli Yuan
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing, 102488, China
| | - Jianmei Huang
- School of Chinese Materia Medica, Beijing University of Chinese Medicine, Liangxiang Town, Fangshan District, Beijing, 102488, China.
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10
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Network toxicology and LC-MS-based metabolomics: New approaches for mechanism of action of toxic components in traditional Chinese medicines. CHINESE HERBAL MEDICINES 2019. [DOI: 10.1016/j.chmed.2019.02.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
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11
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Gong X, Liu M, Gong L, Li Y, Peng C. Study on hepatotoxicity of different dosages of Polygoni multiflori radix praeparata in rats by metabolomics based on UPLC-Q-TOF-MS. J Pharm Biomed Anal 2019; 175:112760. [DOI: 10.1016/j.jpba.2019.07.008] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2019] [Revised: 07/02/2019] [Accepted: 07/05/2019] [Indexed: 01/19/2023]
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12
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Seerangaiyan K, Maruthamuthu M, van Winkelhoff AJ, Winkel EG. Untargeted metabolomics of the bacterial tongue coating of intra-oral halitosis patients. J Breath Res 2019; 13:046010. [DOI: 10.1088/1752-7163/ab334e] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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13
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Reddy P, Rochfort S, Read E, Deseo M, Jaehne E, Van Den Buuse M, Guthridge K, Combs M, Spangenberg G, Quinn J. Tremorgenic effects and functional metabolomics analysis of lolitrem B and its biosynthetic intermediates. Sci Rep 2019; 9:9364. [PMID: 31249318 PMCID: PMC6597573 DOI: 10.1038/s41598-019-45170-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2018] [Accepted: 05/30/2019] [Indexed: 01/02/2023] Open
Abstract
The neuroactive mycotoxin lolitrem B causes a neurological syndrome in grazing livestock resulting in hyperexcitability, muscle tremors, ataxia and, in severe cases, clonic seizures and death. To define the effects of the major toxin lolitrem B in the brain, a functional metabolomic study was undertaken in which motor coordination and tremor were quantified and metabolomic profiling undertaken to determine relative abundance of both toxin and key neurotransmitters in various brain regions in male mice. Marked differences were observed in the duration of tremor and coordination between lolitrem B pathway members, with some showing protracted effects and others none at all. Lolitrem B was identified in liver, kidney, cerebral cortex and thalamus but not in brainstem or cerebellum which were hypothesised previously to be the primary site of action. Metabolomic profiling showed significant variation in specific neurotransmitter and amino acid profiles over time. This study demonstrates accumulation of lolitrem B in the brain, with non-detectable levels of toxin in the brainstem and cerebellum, inducing alterations in metabolites such as tyrosine, suggesting a dynamic catecholaminergic response over time. Temporal characterisation of key pathways in the pathophysiological response of lolitrem B in the brain were also identified.
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Affiliation(s)
- Priyanka Reddy
- Agriculture Victoria, AgriBio, Centre for AgriBioscience, Bundoora, Victoria, 3083, Australia
- School of Applied Systems Biology, La Trobe University, Bundoora, Victoria, 3083, Australia
| | - Simone Rochfort
- Agriculture Victoria, AgriBio, Centre for AgriBioscience, Bundoora, Victoria, 3083, Australia.
- School of Applied Systems Biology, La Trobe University, Bundoora, Victoria, 3083, Australia.
| | - Elizabeth Read
- Agriculture Victoria, AgriBio, Centre for AgriBioscience, Bundoora, Victoria, 3083, Australia
- School of Applied Systems Biology, La Trobe University, Bundoora, Victoria, 3083, Australia
| | - Myrna Deseo
- Agriculture Victoria, AgriBio, Centre for AgriBioscience, Bundoora, Victoria, 3083, Australia
| | - Emily Jaehne
- School of Psychology and Public Health, La Trobe University, Bundoora, Victoria, 3083, Australia
| | - Maarten Van Den Buuse
- School of Psychology and Public Health, La Trobe University, Bundoora, Victoria, 3083, Australia
| | - Kathryn Guthridge
- Agriculture Victoria, AgriBio, Centre for AgriBioscience, Bundoora, Victoria, 3083, Australia
| | - Martin Combs
- School of Animal and Veterinary Sciences, Charles Sturt University, Wagga Wagga, NSW, 2678, Australia
- Graham Centre for Agricultural Innovation, Charles Sturt University, Wagga Wagga, NSW, 2650, Australia
| | - German Spangenberg
- Agriculture Victoria, AgriBio, Centre for AgriBioscience, Bundoora, Victoria, 3083, Australia
- School of Applied Systems Biology, La Trobe University, Bundoora, Victoria, 3083, Australia
| | - Jane Quinn
- School of Animal and Veterinary Sciences, Charles Sturt University, Wagga Wagga, NSW, 2678, Australia
- Graham Centre for Agricultural Innovation, Charles Sturt University, Wagga Wagga, NSW, 2650, Australia
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14
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Roh C, Nguyen TT, Shim JJ, Kang C. Physico-chemical characterization of caesium and strontium using fluorescent intensity of bacteria in a microfluidic platform. ROYAL SOCIETY OPEN SCIENCE 2019; 6:182069. [PMID: 31218033 PMCID: PMC6549985 DOI: 10.1098/rsos.182069] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/11/2019] [Accepted: 04/05/2019] [Indexed: 06/09/2023]
Abstract
Recently, the impact of radioactive caesium (Cs) and strontium (Sr) on human health and the ecosystem has been a major concern due to the use of nuclear energy. However, this study observed changes in green-fluorescent (GFP)-tagged Pseudomonas aeruginosa PAO1 biofilms by injecting non-radioactive caesium chloride (CsCl) and strontium chloride (SrCl2) into microstructures embedded in polydimethylsiloxane microfluidic devices, which were used due to their strong toxicity limitations. Four types of microstructures with two different diameters were used in the study. The change of biofilm thickness from fluid velocity and wall shear stress was estimated using computational fluid dynamics and observed throughout the experiment. The effect of pore space became a significant physical factor when the fluid was flowing through the microfluidic devices. As the pore space increased, the biofilm growth increased; therefore, triangular microstructures with the largest pore space showed the best growth of biofilm. Caesium chloride (CsCl) and strontium chloride (SrCl2), less toxic than radioactive caesium (Cs) and strontium (Sr), completely eradicated the P. aeruginosa PAO1 biofilm with low concentrations. The combined effect of toxicity, fluid velocity, wall shear stress and microstructures increased the efficiency of biofilm eradication. These findings on microfluidic chips can help to indirectly predict the impact on human public health and ecosystems without using radioactive chemicals.
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Affiliation(s)
- Changhyun Roh
- Decommissioning Technology Research Division, Korea Atomic Energy Research Institute (KAERI), 989-111 Daedukdaero, Yuseong, Daejeon 34057, South Korea
- Biotechnology Research Division, Advanced Radiation Technology Institute (ARTI), Korea Atomic Energy Research Institute (KAERI), 29 Geumgu-gil, Jeongeup, Jeonbuk 56212, South Korea
| | - Thi Toan Nguyen
- School of Chemical Engineering, Yeungnam University, 280 Daehak-ro, Gyeonsan, Gyeongbuk 38541, South Korea
| | - Jae-Jin Shim
- School of Chemical Engineering, Yeungnam University, 280 Daehak-ro, Gyeonsan, Gyeongbuk 38541, South Korea
| | - Chankyu Kang
- Office for Government Prime Minister's Secretariat, Service for Promoting Safety of People's Lives, 261 Dasom-ro, Sejong 30107, South Korea
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15
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Luo H, Gu C, Liu C, Wang Y, Wang H, Li Y. Plasma metabolic profiling analysis of Strychnos nux-vomica Linn. and Tripterygium wilfordii Hook F-induced renal toxicity using metabolomics coupled with UPLC/Q-TOF-MS. Toxicol Res (Camb) 2018; 7:1153-1163. [PMID: 30510685 PMCID: PMC6220728 DOI: 10.1039/c8tx00115d] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Accepted: 07/25/2018] [Indexed: 12/19/2022] Open
Abstract
Both Strychnos nux-vomica Linn. (SNV) and Tripterygium wilfordii Hook F (TwHF) have received extensive attention due to their excellent clinical efficacies. However, clinical applications of SNV and TwHF have been limited by their narrow therapeutic windows and severe kidney toxicities. In this paper, based on ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS), endogenous metabolites after administration of SNV and TwHF extracts were detected, and biomarkers were screened successfully. Additionally, the levels of Cr and BUN in serum and pathological findings of kidneys were detected and observed. Finally, both biochemical and pathological tests of the SNV group and TwHF group indicated that kidney damage had occurred. After comparison with the normal saline group, 15 nephrotoxic biomarkers were selected from the SNV group, and 17 nephrotoxic biomarkers were selected from the TwHF group. The experimental results showed that there are some differences in the mechanisms of nephrotoxicity induced by SNV and TwHF, which are significant for revealing the mechanisms of renal injury of different medicines.
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Affiliation(s)
- Houmin Luo
- School of Chinese Materia Medica , Tianjin University of Traditional Chinese Medicine , 312 Anshan West Road , Nankai District , Tianjin 300193 , China . ;
- Tianjin State Key Laboratory of Modern Chinese Medicine , Tianjin University of Traditional Chinese Medicine , No. 88 , Yuquan Road , Nankai District , Tianjin 300193 , China
| | - Caiyun Gu
- School of Chinese Materia Medica , Tianjin University of Traditional Chinese Medicine , 312 Anshan West Road , Nankai District , Tianjin 300193 , China . ;
- Tianjin State Key Laboratory of Modern Chinese Medicine , Tianjin University of Traditional Chinese Medicine , No. 88 , Yuquan Road , Nankai District , Tianjin 300193 , China
| | - Chuanxin Liu
- School of Chinese Materia Medica , Tianjin University of Traditional Chinese Medicine , 312 Anshan West Road , Nankai District , Tianjin 300193 , China . ;
- Tianjin State Key Laboratory of Modern Chinese Medicine , Tianjin University of Traditional Chinese Medicine , No. 88 , Yuquan Road , Nankai District , Tianjin 300193 , China
| | - Yuming Wang
- School of Chinese Materia Medica , Tianjin University of Traditional Chinese Medicine , 312 Anshan West Road , Nankai District , Tianjin 300193 , China . ;
- Tianjin State Key Laboratory of Modern Chinese Medicine , Tianjin University of Traditional Chinese Medicine , No. 88 , Yuquan Road , Nankai District , Tianjin 300193 , China
| | - Hao Wang
- School of Chinese Materia Medica , Tianjin University of Traditional Chinese Medicine , 312 Anshan West Road , Nankai District , Tianjin 300193 , China . ;
- Tianjin State Key Laboratory of Modern Chinese Medicine , Tianjin University of Traditional Chinese Medicine , No. 88 , Yuquan Road , Nankai District , Tianjin 300193 , China
| | - Yubo Li
- School of Chinese Materia Medica , Tianjin University of Traditional Chinese Medicine , 312 Anshan West Road , Nankai District , Tianjin 300193 , China . ;
- Tianjin State Key Laboratory of Modern Chinese Medicine , Tianjin University of Traditional Chinese Medicine , No. 88 , Yuquan Road , Nankai District , Tianjin 300193 , China
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16
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Vincenzi B, Russo A, Terenzio A, Galvano A, Santini D, Vorini F, Antonelli-Incalzi R, Vespasiani-Gentilucci U, Tonini G. The use of SAMe in chemotherapy-induced liver injury. Crit Rev Oncol Hematol 2018; 130:70-77. [PMID: 30196914 DOI: 10.1016/j.critrevonc.2018.06.019] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2018] [Revised: 06/22/2018] [Accepted: 06/25/2018] [Indexed: 02/07/2023] Open
Abstract
Drug-induced liver injury (DILI) remains the most common cause of acute liver failure in the Western world. Chemotherapy is one of the major class of drugs most frequently associated with idiosyncratic DILI. For this reason, patients who receive chemotherapy require careful assessment of liver function prior to treatment to determine which drugs may not be appropriate and which drug doses should be modified. S-adenosylmethionine (SAMe) is an endogenous agent derived from methionine. Its supplementation is effective in the treatment of liver disease, in particular intrahepatic cholestasis (IHC). The target of this review is to analyze the mechanisms of hepatotoxicity of the principal anticancer agents and the role of SAMe in the prevention of this complication.
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Affiliation(s)
- B Vincenzi
- Medical Oncology Unit, Campus Bio-Medico University, Rome, Italy.
| | - A Russo
- Department of Surgery and Oncology, Section of Medical Oncology, University of Palermo, Italy
| | - A Terenzio
- Medical Oncology Unit, Campus Bio-Medico University, Rome, Italy
| | - A Galvano
- Department of Surgery and Oncology, Section of Medical Oncology, University of Palermo, Italy
| | - D Santini
- Medical Oncology Unit, Campus Bio-Medico University, Rome, Italy
| | - F Vorini
- Interdisciplinary Center for Biomedical Research (CIR), Laboratory of Internal Medicine and Hepatology, Campus Bio-Medico University, Rome, Italy
| | | | - U Vespasiani-Gentilucci
- Interdisciplinary Center for Biomedical Research (CIR), Laboratory of Internal Medicine and Hepatology, Campus Bio-Medico University, Rome, Italy
| | - G Tonini
- Medical Oncology Unit, Campus Bio-Medico University, Rome, Italy
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17
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Xu Y, Zhao Y, Guo X, Li Y, Zhang Y. Plasma metabolic profiling analysis of neurotoxicity induced by oxaliplatin using metabonomics and multivariate data analysis. Toxicol Res (Camb) 2018; 7:529-537. [PMID: 30090603 PMCID: PMC6060739 DOI: 10.1039/c7tx00345e] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2017] [Accepted: 04/02/2018] [Indexed: 12/11/2022] Open
Abstract
Oxaliplatin is a third generation antitumor agent, which is often used in treating advanced colorectal cancer, but the use of oxaliplatin is limited by its side effects, especially peripheral nerve toxicity. Metabonomics techniques, as a holistic analytical technique, could provide basic information on the metabolic profile of biological fluids during drug administration. In this study, we used the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) technique to analyze rat plasma samples collected seven days after oxaliplatin administration. The changes of metabolites in plasma samples were evaluated by principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA), and 15 kinds of neurotoxicity-related biomarkers were screened. The metabolic pathways of interference involved amino acid biosynthesis and metabolism, glycerophospholipid metabolism, sphingolipid metabolism and so on. The biomarkers found in this study are significant for the study of neurotoxicity.
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Affiliation(s)
- Yanyan Xu
- School of Chinese Materia Medica , Tianjin University of Traditional Chinese Medicine , 312 Anshan West Road , Nankai District , Tianjin 300193 , China
- Tianjin State Key Laboratory of Modern Chinese Medicine , Tianjin University of Traditional Chinese Medicine , No. 88 , Yuquan Road , Nankai District , Tianjin 300193 , China . ;
| | - Yiwei Zhao
- School of Chinese Materia Medica , Tianjin University of Traditional Chinese Medicine , 312 Anshan West Road , Nankai District , Tianjin 300193 , China
- Tianjin State Key Laboratory of Modern Chinese Medicine , Tianjin University of Traditional Chinese Medicine , No. 88 , Yuquan Road , Nankai District , Tianjin 300193 , China . ;
| | - Xuejun Guo
- School of Chinese Materia Medica , Tianjin University of Traditional Chinese Medicine , 312 Anshan West Road , Nankai District , Tianjin 300193 , China
- Tianjin State Key Laboratory of Modern Chinese Medicine , Tianjin University of Traditional Chinese Medicine , No. 88 , Yuquan Road , Nankai District , Tianjin 300193 , China . ;
| | - Yubo Li
- School of Chinese Materia Medica , Tianjin University of Traditional Chinese Medicine , 312 Anshan West Road , Nankai District , Tianjin 300193 , China
- Tianjin State Key Laboratory of Modern Chinese Medicine , Tianjin University of Traditional Chinese Medicine , No. 88 , Yuquan Road , Nankai District , Tianjin 300193 , China . ;
| | - Yanjun Zhang
- Tianjin State Key Laboratory of Modern Chinese Medicine , Tianjin University of Traditional Chinese Medicine , No. 88 , Yuquan Road , Nankai District , Tianjin 300193 , China . ;
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18
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Zhang PJ, Li YM, Zhang YN, Huang W, Li YB, Zhang YJ, Liu CX. Application and prospect of toxicity quality markers of Chinese materia medica based on metabolomics. CHINESE HERBAL MEDICINES 2018. [DOI: 10.1016/j.chmed.2018.02.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
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19
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Xu Y, Zhao Y, Xie J, Sheng X, Li Y, Zhang Y. The Evaluation of Toxicity Induced by Psoraleae Fructus in Rats Using Untargeted Metabonomic Method Based on UPLC-Q-TOF/MS. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2017; 2017:6207183. [PMID: 29279717 PMCID: PMC5723950 DOI: 10.1155/2017/6207183] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Accepted: 10/02/2017] [Indexed: 12/25/2022]
Abstract
Psoraleae Fructus is the dry and mature fruit of leguminous plant Psoralea corylifolia L., with the activity of warming kidney and enhancing yang, warming spleen, and other effects. However, large doses can cause liver and kidney toxicity. Therefore, it is necessary to evaluate the toxicity of Psoraleae Fructus systematically. Although traditional biochemical indicators and pathological tests have been used to evaluate the safety of drug, these methods lack sensitivity and specificity, so a fast and sensitive analytical method is urgently needed. In this study, an ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) method was used to analyze the metabolic profiles of rat plasma. The changes of metabolites in plasma samples were detected by partial least squares-discriminant analysis (PLS-DA). Compared with the control group, after 7 days of administration, the pathological sections showed liver and kidney toxicity, and the metabolic trend was changed. Finally, 13 potential biomarkers related to the toxicity of Psoraleae Fructus were screened. The metabolic pathways involved were glycerol phospholipids metabolism, amino acid metabolism, energy metabolism, and so forth. The discovery of these biomarkers laid a foundation for better explaining the hepatotoxicity and nephrotoxicity of Psoraleae Fructus and provided a guarantee for its safety evaluation.
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Affiliation(s)
- Yanyan Xu
- State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, No. 88, Yuquan Road, Nankai District, Tianjin 300193, China
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Nankai District, Tianjin 300193, China
| | - Yiwei Zhao
- State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, No. 88, Yuquan Road, Nankai District, Tianjin 300193, China
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Nankai District, Tianjin 300193, China
| | - Jiabin Xie
- State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, No. 88, Yuquan Road, Nankai District, Tianjin 300193, China
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Nankai District, Tianjin 300193, China
| | - Xue Sheng
- State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, No. 88, Yuquan Road, Nankai District, Tianjin 300193, China
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Nankai District, Tianjin 300193, China
| | - Yubo Li
- State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, No. 88, Yuquan Road, Nankai District, Tianjin 300193, China
- School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Nankai District, Tianjin 300193, China
| | - Yanjun Zhang
- State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, No. 88, Yuquan Road, Nankai District, Tianjin 300193, China
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20
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Wu F, Zheng H, Yang ZT, Cheng B, Wu JX, Liu XW, Tang CL, Lu SY, Chen ZN, Song FM, Ruan JX, Zhang HY, Liang YH, Song H, Su ZH. Urinary metabonomics study of the hepatoprotective effects of total alkaloids from Corydalis saxicola Bunting on carbon tetrachloride-induced chronic hepatotoxicity in rats using 1 H NMR analysis. J Pharm Biomed Anal 2017; 140:199-209. [DOI: 10.1016/j.jpba.2017.03.031] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2016] [Revised: 03/08/2017] [Accepted: 03/15/2017] [Indexed: 02/06/2023]
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21
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Yang S, Cao C, Chen S, Hu L, Bao W, Shi H, Zhao X, Sun C. Serum Metabolomics Analysis of Quercetin against Acrylamide-Induced Toxicity in Rats. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2016; 64:9237-9245. [PMID: 27933994 DOI: 10.1021/acs.jafc.6b04149] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
The current study aimed to investigate whether quercetin plays a protective role in acrylamide (AA)-induced toxicity using a metabolomics approach. Rats were randomly divided into groups as follows: control, treated with AA [5 mg/kg body weight (bw)], treated with different dosages of quercetin (10 and 50 mg/kg bw, respectively), and treated with two dosages of quercetin plus AA. After a 16 week treatment, rat serum was collected for metabolomics analysis. Biochemical tests and examination of liver histopathology were further conducted to verify metabolic alterations. Twelve metabolites were identified for which intensities were significantly changed (increased or reduced) as a result of the treatment. These metabolites included isorhamnetin, citric acid, pantothenic acid, isobutyryl-l-carnitine, eicosapentaenoic acid, docosahexaenoic acid, sphingosine 1-phosphate, lysoPC(20:4), lysoPC(22:6), lysoPE(20:3), undecanedioic acid, and dodecanedioic acid. The results indicate that quercetin (50 mg/kg bw) exerts partial protective effects on AA-induced toxicity by reducing oxidative stress, protecting the mitochondria, and regulating lipid metabolism.
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Affiliation(s)
- Shuang Yang
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University , 150081 Harbin, Heilongjiang, China
| | - Can Cao
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University , 150081 Harbin, Heilongjiang, China
| | - Shuai Chen
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University , 150081 Harbin, Heilongjiang, China
| | - Liyan Hu
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University , 150081 Harbin, Heilongjiang, China
| | - Wei Bao
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University , 150081 Harbin, Heilongjiang, China
| | - Haidan Shi
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University , 150081 Harbin, Heilongjiang, China
| | - Xiujuan Zhao
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University , 150081 Harbin, Heilongjiang, China
| | - Changhao Sun
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University , 150081 Harbin, Heilongjiang, China
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22
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Zhou H, Zhang P, Hou Z, Xie J, Wang Y, Yang B, Xu Y, Li Y. Research on the Relationships between Endogenous Biomarkers and Exogenous Toxic Substances of Acute Toxicity in Radix Aconiti. Molecules 2016; 21:molecules21121623. [PMID: 27898008 PMCID: PMC6273418 DOI: 10.3390/molecules21121623] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2016] [Revised: 11/13/2016] [Accepted: 11/21/2016] [Indexed: 12/14/2022] Open
Abstract
Radix Aconiti, a classic traditional Chinese medicine (TCM), has been widely used throughout China for disease treatment due to its various pharmacological activities, such as anti-inflammatory, cardiotonic, and analgesic effects. However, improper use of Radix Aconiti often generated severe acute toxicity. Currently, research on the toxic substances of Radix Aconiti is not rare. In our previous study, acute toxic biomarkers of Radix Aconiti have been found. However, few studies were available to find the relationships between these endogenous biomarkers and exogenous toxic substances. Therefore, in this study, toxic substances of Radix Aconiti have been found using UPLC-Q-TOF-MS technology. Then, we used biochemical indicators as a bridge to find the relationships between biomarkers and toxic substances of Radix Aconiti through Pearson correlation analysis and canonical correlation analysis (CCA). Finally, the CCA results showed that LysoPC(22:5) is related to 14-acetyl-talatisamine, mesaconitine, talatisamine and deoxyaconitine in varying degrees; l-acetylcarnitine is negatively correlated with deoxyaconitine and demethyl-14-acetylkaracoline; shikimic acid has a good correlation with karacoline, demethyl-14-acetylkaracoline and deoxyaconitine; and valine is correlated with talatisamine and deoxyaconitine. Research on these relationships provides an innovative way to interpret the toxic mechanism of traditional Chinese medicine, and plays a positive role in the overall study of TCM toxicity.
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Affiliation(s)
- Haonan Zhou
- Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
| | - Pengjie Zhang
- Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
| | - Zhiguo Hou
- Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
| | - Jiabin Xie
- Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
| | - Yuming Wang
- Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
| | - Bin Yang
- Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
| | - Yanyan Xu
- Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
| | - Yubo Li
- Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
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23
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Zhang Z, Zhang Y, Yin J, Li Y. An integrated strategy for the rapid extraction and screening of phosphatidylcholines and lysophosphatidylcholines using semi-automatic solid phase extraction and data processing technology. J Chromatogr A 2016; 1461:192-7. [PMID: 27475993 DOI: 10.1016/j.chroma.2016.07.037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2016] [Revised: 07/13/2016] [Accepted: 07/14/2016] [Indexed: 10/21/2022]
Abstract
This study attempts to establish a comprehensive strategy for the rapid extraction and screening of phosphatidylcholines (PCs) and lysophosphatidylcholines (LysoPCs) in biological samples using semi-automatic solid phase extraction (SPE) and data processing technology based on ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF-MS). First, the Ostro sample preparation method (i.e., semi-automatic SPE) was compared with the Bligh-Dyer method in terms of substance coverage, reproducibility and sample preparation time. Meanwhile, the screening method for PCs and LysoPCs was built through mass range screening, mass defect filtering and diagnostic fragments filtering. Then, the Ostro sample preparation method and the aforementioned screening method were combined under optimal conditions to establish a rapid extraction and screening platform. Finally, this developed method was validated and applied to the preparation and data analysis of tissue samples. Through a systematic evaluation, this developed method was shown to provide reliable and high-throughput experimental results and was suitable for the preparation and analysis of tissue samples. Our method provides a novel strategy for the rapid extraction and analysis of functional phospholipids. In addition, this study will promote further study of phospholipids in disease research.
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Affiliation(s)
- Zhenzhu Zhang
- Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China
| | - Yani Zhang
- Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China
| | - Jia Yin
- Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China
| | - Yubo Li
- Tianjin State Key Laboratory of Modern Chinese Medicine, School of Traditional Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, 312 Anshan West Road, Tianjin 300193, China.
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24
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Robles-Díaz M, Medina-Caliz I, Stephens C, Andrade RJ, Lucena MI. Biomarkers in DILI: One More Step Forward. Front Pharmacol 2016; 7:267. [PMID: 27597831 PMCID: PMC4992729 DOI: 10.3389/fphar.2016.00267] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2016] [Accepted: 08/08/2016] [Indexed: 12/11/2022] Open
Abstract
Despite being relatively rare, drug-induced liver injury (DILI) is a serious condition, both for the individual patient due to the risk of acute liver failure, and for the drug development industry and regulatory agencies due to associations with drug development attritions, black box warnings, and postmarketing withdrawals. A major limitation in DILI diagnosis and prediction is the current lack of specific biomarkers. Despite refined usage of traditional liver biomarkers in DILI, reliable disease outcome predictions are still difficult to make. These limitations have driven the growing interest in developing new more sensitive and specific DILI biomarkers, which can improve early DILI prediction, diagnosis, and course of action. Several promising DILI biomarker candidates have been discovered to date, including mechanistic-based biomarker candidates such as glutamate dehydrogenase, high-mobility group box 1 protein and keratin-18, which can also provide information on the injury mechanism of different causative agents. Furthermore, microRNAs have received much attention lately as potential non-invasive DILI biomarker candidates, in particular miR-122. Advances in “omics” technologies offer a new approach for biomarker exploration studies. The ability to screen a large number of molecules (e.g., metabolites, proteins, or DNA) simultaneously enables the identification of ‘toxicity signatures,’ which may be used to enhance preclinical safety assessments and disease diagnostics. Omics-based studies can also provide information on the underlying mechanisms of distinct forms of DILI that may further facilitate the identification of early diagnostic biomarkers and safer implementation of personalized medicine. In this review, we summarize recent advances in the area of DILI biomarker studies.
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Affiliation(s)
- Mercedes Robles-Díaz
- Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas Málaga, Spain
| | - Inmaculada Medina-Caliz
- Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas Málaga, Spain
| | - Camilla Stephens
- Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas Málaga, Spain
| | - Raúl J Andrade
- Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas Málaga, Spain
| | - M Isabel Lucena
- Unidad de Gestión Clínica de Aparato Digestivo, Servicio de Farmacología Clínica, Instituto de Investigación Biomédica de Málaga, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas Málaga, Spain
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