Hepatotoxicity and mechanism study of chrysophanol-8-O-glucoside in vitro

To better understand the hepatotoxicity of anthraquinone glycosides, the hepatotoxicity of six anthraquinone glycosides was evaluated. The results show that chrysophanol-8-O-glucoside(C8G) has strong hepatotoxicity and can lead to increased LDH leakage and ROS, decreased GSH and MMP in L-02 hepatocy...

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Bibliographic Details
Published in:Biomedicine & pharmacotherapy 2019-12, Vol.120, p.109531, Article 109531
Main Authors: Lin, Longfei, yuan, Fang, Liu, Yuling, Zhong, Ming, Xie, Tanggui, Ni, Jian, Li, Hui
Format: Article
Language:English
Subjects:
Anthraquinone glycosides
Anthraquinones - chemistry
Anthraquinones - toxicity
Cell Line
chrysophanol-8-O-glucoside
Electron Transport - drug effects
Gene Ontology
Glucosides - chemistry
Glucosides - toxicity
Hepatotoxicity
Humans
L-Lactate Dehydrogenase - metabolism
Liver - drug effects
Liver - pathology
Matrix Metalloproteinases - metabolism
Mitochondria - drug effects
Mitochondria - metabolism
Mitochondrial
Proteomic
Reactive Oxygen Species - metabolism
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Summary:To better understand the hepatotoxicity of anthraquinone glycosides, the hepatotoxicity of six anthraquinone glycosides was evaluated. The results show that chrysophanol-8-O-glucoside(C8G) has strong hepatotoxicity and can lead to increased LDH leakage and ROS, decreased GSH and MMP in L-02 hepatocytes. The results of C8G hepatotoxicity proteomics shows that, a total of 773 differentially expressed proteins were screened and analyzed using GO analysis and Pathway enrichment analysis. Our results show that C8G can lead to abnormal oxidative phosphorylation by inhibiting the function of mitochondrial complexes, resulting in decreased mitochondrial membrane potential (MMP), increased reactive oxygen species (ROS), and eventually resulting in mitochondrial damage and apoptosis. Western blot results verified the accuracy of quantitative proteomic results, and also evaluated the expression of Bax, caspase-3, -8, -9, Bcl-2, Cyt C in the mitochondria and cytosolic. The mitochondrial respiratory chain complexes activity assay result also confirmed that C8G could inhibit the activity of all mitochondrial complexes. The results of this study indicate that the hepatotoxicity mechanism of C8G is related to mitochondrial dysfunction, especially the mitochondrial complex function.
ISSN:0753-3322
1950-6007
DOI:10.1016/j.biopha.2019.109531