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Combined Metabolomics and Network Toxicology to Explore the Molecular Mechanism of Phytolacca acinose Roxb-Induced Hepatotoxicity in Zebrafish Larvae in Vivo

Phytolacca acinosa Roxb (PAR), a traditional Chinese medicine, has been widely used as a diuretic drug for a long period of time for the treatment edema, swelling, and sores. However, it has been reported that PAR might induce hepatotoxicity, while the mechanisms of its toxic effect are still unclea...

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Autores principales: Cao, Dan, Zhao, Chongjun, Li, Zhiqi, Fan, Qiqi, Chen, Meilin, Jiang, Yangyu, Wang, Haiyan, Ning, Hanjun, Lin, Ruichao, Li, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645354/
https://www.ncbi.nlm.nih.gov/pubmed/34876912
http://dx.doi.org/10.1155/2021/3303014
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author Cao, Dan
Zhao, Chongjun
Li, Zhiqi
Fan, Qiqi
Chen, Meilin
Jiang, Yangyu
Wang, Haiyan
Ning, Hanjun
Lin, Ruichao
Li, Jian
author_facet Cao, Dan
Zhao, Chongjun
Li, Zhiqi
Fan, Qiqi
Chen, Meilin
Jiang, Yangyu
Wang, Haiyan
Ning, Hanjun
Lin, Ruichao
Li, Jian
author_sort Cao, Dan
collection PubMed
description Phytolacca acinosa Roxb (PAR), a traditional Chinese medicine, has been widely used as a diuretic drug for a long period of time for the treatment edema, swelling, and sores. However, it has been reported that PAR might induce hepatotoxicity, while the mechanisms of its toxic effect are still unclear. In this study, network toxicology and metabolomic technique were applied to explore PAR-induced hepatotoxicity on zebrafish larvae. We evaluated the effect of PAR on the ultrastructure and the function of the liver, predictive targets, and pathways in network toxicology, apoptosis of liver cells by PCR and western blot, and metabolic profile by GC-MS. PAR causes liver injury, abnormal liver function, and apoptosis in zebrafish. The level of arachidonic acid in endogenous metabolites treated with PAR was significantly increased, leading to oxidative stress in vivo. Excessive ROS further activated the p53 signal pathway and caspase family, which were obtained from KEGG enrichment analysis of network toxicology. The gene levels of caspase-3, caspase-8, and caspase-9 were significantly increased by RT-PCR, and the level of Caps3 protein was also significantly up-regulated through western blot. PAR exposure results in the liver function abnormal amino acid metabolism disturbance and motivates hepatocyte apoptosis, furthermore leading to liver injury.
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spelling pubmed-86453542021-12-06 Combined Metabolomics and Network Toxicology to Explore the Molecular Mechanism of Phytolacca acinose Roxb-Induced Hepatotoxicity in Zebrafish Larvae in Vivo Cao, Dan Zhao, Chongjun Li, Zhiqi Fan, Qiqi Chen, Meilin Jiang, Yangyu Wang, Haiyan Ning, Hanjun Lin, Ruichao Li, Jian Evid Based Complement Alternat Med Research Article Phytolacca acinosa Roxb (PAR), a traditional Chinese medicine, has been widely used as a diuretic drug for a long period of time for the treatment edema, swelling, and sores. However, it has been reported that PAR might induce hepatotoxicity, while the mechanisms of its toxic effect are still unclear. In this study, network toxicology and metabolomic technique were applied to explore PAR-induced hepatotoxicity on zebrafish larvae. We evaluated the effect of PAR on the ultrastructure and the function of the liver, predictive targets, and pathways in network toxicology, apoptosis of liver cells by PCR and western blot, and metabolic profile by GC-MS. PAR causes liver injury, abnormal liver function, and apoptosis in zebrafish. The level of arachidonic acid in endogenous metabolites treated with PAR was significantly increased, leading to oxidative stress in vivo. Excessive ROS further activated the p53 signal pathway and caspase family, which were obtained from KEGG enrichment analysis of network toxicology. The gene levels of caspase-3, caspase-8, and caspase-9 were significantly increased by RT-PCR, and the level of Caps3 protein was also significantly up-regulated through western blot. PAR exposure results in the liver function abnormal amino acid metabolism disturbance and motivates hepatocyte apoptosis, furthermore leading to liver injury. Hindawi 2021-11-28 /pmc/articles/PMC8645354/ /pubmed/34876912 http://dx.doi.org/10.1155/2021/3303014 Text en Copyright © 2021 Dan Cao et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Cao, Dan
Zhao, Chongjun
Li, Zhiqi
Fan, Qiqi
Chen, Meilin
Jiang, Yangyu
Wang, Haiyan
Ning, Hanjun
Lin, Ruichao
Li, Jian
Combined Metabolomics and Network Toxicology to Explore the Molecular Mechanism of Phytolacca acinose Roxb-Induced Hepatotoxicity in Zebrafish Larvae in Vivo
title Combined Metabolomics and Network Toxicology to Explore the Molecular Mechanism of Phytolacca acinose Roxb-Induced Hepatotoxicity in Zebrafish Larvae in Vivo
title_full Combined Metabolomics and Network Toxicology to Explore the Molecular Mechanism of Phytolacca acinose Roxb-Induced Hepatotoxicity in Zebrafish Larvae in Vivo
title_fullStr Combined Metabolomics and Network Toxicology to Explore the Molecular Mechanism of Phytolacca acinose Roxb-Induced Hepatotoxicity in Zebrafish Larvae in Vivo
title_full_unstemmed Combined Metabolomics and Network Toxicology to Explore the Molecular Mechanism of Phytolacca acinose Roxb-Induced Hepatotoxicity in Zebrafish Larvae in Vivo
title_short Combined Metabolomics and Network Toxicology to Explore the Molecular Mechanism of Phytolacca acinose Roxb-Induced Hepatotoxicity in Zebrafish Larvae in Vivo
title_sort combined metabolomics and network toxicology to explore the molecular mechanism of phytolacca acinose roxb-induced hepatotoxicity in zebrafish larvae in vivo
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8645354/
https://www.ncbi.nlm.nih.gov/pubmed/34876912
http://dx.doi.org/10.1155/2021/3303014
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