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The Increase of ROS Caused by the Interference of DEHP with JNK/p38/p53 Pathway as the Reason for Hepatotoxicity

As the most commonly used plasticizer, Di-(2-ethylhexyl)-phthalate (DEHP) exists everywhere in the environment due to the widespread use of polyvinyl chloride (PVC) in human life, and it is also a recognized environmental pollutant. Studies have proved the hepatotoxicity of DEHP, however the mechani...

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Autores principales: Huang, Yuanyuan, Wu, Chuancheng, Ye, Youbin, Zeng, Jingwen, Zhu, Jianlin, Li, Yuchen, Wang, Wenxiang, Zhang, Wenchang, Chen, Yiqin, Xie, Hongyuan, Zhang, Hongmei, Liu, Jin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388128/
https://www.ncbi.nlm.nih.gov/pubmed/30691201
http://dx.doi.org/10.3390/ijerph16030356
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author Huang, Yuanyuan
Wu, Chuancheng
Ye, Youbin
Zeng, Jingwen
Zhu, Jianlin
Li, Yuchen
Wang, Wenxiang
Zhang, Wenchang
Chen, Yiqin
Xie, Hongyuan
Zhang, Hongmei
Liu, Jin
author_facet Huang, Yuanyuan
Wu, Chuancheng
Ye, Youbin
Zeng, Jingwen
Zhu, Jianlin
Li, Yuchen
Wang, Wenxiang
Zhang, Wenchang
Chen, Yiqin
Xie, Hongyuan
Zhang, Hongmei
Liu, Jin
author_sort Huang, Yuanyuan
collection PubMed
description As the most commonly used plasticizer, Di-(2-ethylhexyl)-phthalate (DEHP) exists everywhere in the environment due to the widespread use of polyvinyl chloride (PVC) in human life, and it is also a recognized environmental pollutant. Studies have proved the hepatotoxicity of DEHP, however the mechanism has not been adequately explored, especially the role of the reactive oxygen species (ROS) in it. In the present study, 21 day-old ICR mice were administered DEHP with dose of 0, 125, 250, and 375 mg/kg/day for 28 days by intragastrical gavage. After contamination, histopathology displayed that liver tissue were damaged mildly with the effect of DEHP; a significant increase of the serum liver function index (including aspartate transaminase (AST) and alanine transaminase (ALT)) were observed. Additionally, the level of lipid peroxidation markedly rise, especially ROS and malondialdehyde (MDA), but the activation of superoxide dismutase (SOD) was obviously decreased in mice liver. In addition, DEHP promoted the phosphorylation of JNK and p38MAPK proteins in mice liver, as well as increased the expression of p53 protein and decreased the level of DNA methylation in the p53 gene promoter region. These results indicated that the hepatotoxicity of mice caused by DEHP may be through activating the JNK/p38MAPK/p53 signaling pathway and further promoting the generation of ROS to induce lipid peroxidation in liver, and the role of DNA methylation may be inevitable.
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spelling pubmed-63881282019-02-27 The Increase of ROS Caused by the Interference of DEHP with JNK/p38/p53 Pathway as the Reason for Hepatotoxicity Huang, Yuanyuan Wu, Chuancheng Ye, Youbin Zeng, Jingwen Zhu, Jianlin Li, Yuchen Wang, Wenxiang Zhang, Wenchang Chen, Yiqin Xie, Hongyuan Zhang, Hongmei Liu, Jin Int J Environ Res Public Health Article As the most commonly used plasticizer, Di-(2-ethylhexyl)-phthalate (DEHP) exists everywhere in the environment due to the widespread use of polyvinyl chloride (PVC) in human life, and it is also a recognized environmental pollutant. Studies have proved the hepatotoxicity of DEHP, however the mechanism has not been adequately explored, especially the role of the reactive oxygen species (ROS) in it. In the present study, 21 day-old ICR mice were administered DEHP with dose of 0, 125, 250, and 375 mg/kg/day for 28 days by intragastrical gavage. After contamination, histopathology displayed that liver tissue were damaged mildly with the effect of DEHP; a significant increase of the serum liver function index (including aspartate transaminase (AST) and alanine transaminase (ALT)) were observed. Additionally, the level of lipid peroxidation markedly rise, especially ROS and malondialdehyde (MDA), but the activation of superoxide dismutase (SOD) was obviously decreased in mice liver. In addition, DEHP promoted the phosphorylation of JNK and p38MAPK proteins in mice liver, as well as increased the expression of p53 protein and decreased the level of DNA methylation in the p53 gene promoter region. These results indicated that the hepatotoxicity of mice caused by DEHP may be through activating the JNK/p38MAPK/p53 signaling pathway and further promoting the generation of ROS to induce lipid peroxidation in liver, and the role of DNA methylation may be inevitable. MDPI 2019-01-27 2019-02 /pmc/articles/PMC6388128/ /pubmed/30691201 http://dx.doi.org/10.3390/ijerph16030356 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Huang, Yuanyuan
Wu, Chuancheng
Ye, Youbin
Zeng, Jingwen
Zhu, Jianlin
Li, Yuchen
Wang, Wenxiang
Zhang, Wenchang
Chen, Yiqin
Xie, Hongyuan
Zhang, Hongmei
Liu, Jin
The Increase of ROS Caused by the Interference of DEHP with JNK/p38/p53 Pathway as the Reason for Hepatotoxicity
title The Increase of ROS Caused by the Interference of DEHP with JNK/p38/p53 Pathway as the Reason for Hepatotoxicity
title_full The Increase of ROS Caused by the Interference of DEHP with JNK/p38/p53 Pathway as the Reason for Hepatotoxicity
title_fullStr The Increase of ROS Caused by the Interference of DEHP with JNK/p38/p53 Pathway as the Reason for Hepatotoxicity
title_full_unstemmed The Increase of ROS Caused by the Interference of DEHP with JNK/p38/p53 Pathway as the Reason for Hepatotoxicity
title_short The Increase of ROS Caused by the Interference of DEHP with JNK/p38/p53 Pathway as the Reason for Hepatotoxicity
title_sort increase of ros caused by the interference of dehp with jnk/p38/p53 pathway as the reason for hepatotoxicity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388128/
https://www.ncbi.nlm.nih.gov/pubmed/30691201
http://dx.doi.org/10.3390/ijerph16030356
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