Study on potential toxic material base and mechanisms of hepatotoxicity induced by Dysosma versipellis based on toxicological evidence chain (TEC) concept
| Autor: | Wenxin Wang, Qiang Wang, Lu Sun, Fuli Yuan, Chuanxin Liu, Jiao Kong, Shuang Han, Tao He, Chenning Zhang, Jianmei Huang |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Health Toxicology and Mutagenesis Phytochemicals SOD1 0211 other engineering and technologies SOD2 Apoptosis 02 engineering and technology 010501 environmental sciences Pharmacology medicine.disease_cause 01 natural sciences Metabolomics Detoxification medicine Animals Medicine Chinese Traditional Rats Wistar 0105 earth and related environmental sciences 021110 strategic defence & security studies Chemistry Mechanism (biology) Public Health Environmental and Occupational Health General Medicine Berberidaceae Pollution Molecular Docking Simulation Oxidative Stress Podophyllotoxin Toxicity Chemical and Drug Induced Liver Injury Energy Metabolism Oxidative stress medicine.drug |
| Zdroj: | Ecotoxicology and Environmental Safety. 190:110073 |
| ISSN: | 0147-6513 |
| DOI: | 10.1016/j.ecoenv.2019.110073 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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