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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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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. |
format | Online Article Text |
id | pubmed-6388128 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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