Systems Toxicology Approaches Reveal the Mechanisms of Hepatotoxicity Induced by Diosbulbin B in Male Mice
| Autor: | Lei Zhang, Juan Ren, Hua Li, Guolin Shen, Baoliang Xu, Naining Song, Wentao Li, Hainan Ji, Haishan Li |
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| Rok vydání: | 2020 |
| Předmět: |
Male
medicine.medical_specialty Mitochondria Liver 010501 environmental sciences Carbohydrate metabolism Mitochondrion Pharmacology Toxicology Heterocyclic Compounds 4 or More Rings 01 natural sciences 03 medical and health sciences Metabolomics medicine Animals Cytochrome P-450 CYP3A 030304 developmental biology 0105 earth and related environmental sciences Adenosine Triphosphatases chemistry.chemical_classification Mice Inbred ICR 0303 health sciences Mechanism (biology) Systems Biology Fatty Acids Membrane Proteins Fatty acid General Medicine Mice Inbred C57BL Molecular Docking Simulation Citric acid cycle Glucose Enzyme Liver chemistry Histopathology Chemical and Drug Induced Liver Injury |
| Zdroj: | Chemical Research in Toxicology. 33:1389-1402 |
| ISSN: | 1520-5010 0893-228X |
| DOI: | 10.1021/acs.chemrestox.9b00503 |
| Popis: | Diosbulbin B (DIOB) is an effective component of air potato yam with antitumor and anti-inflammatory activities, and it is the main toxic component leading to hepatotoxicity. However, the mechanism of its hepatotoxicity remains unclear. In this study, we aimed to systematically elucidate the molecular action of DIOB on liver metabolic function through systems toxicology approaches. C57BL/6 mice were orally treated with DIOB (10, 30, 60 mg/kg) for 28 days, and the liver metabonomics and histopathology, molecular docking, mRNA expression levels, and activities of enzymes were analyzed. The results illustrated that DIOB could affect fatty acid and glucose metabolism, block the TCA cycle, and DIOB also could disorder bile acid synthesis and transport and promote the occurrence of hyperbilirubinemia. In addition, DIOB increased Cyp3a11 expression in a dose-dependent manner. Thus, these results provide new insights into the mechanism of hepatotoxicity caused by DIOB. |
| Databáze: | OpenAIRE |
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