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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2019-01-01
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Series: | International Journal of Environmental Research and Public Health |
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Online Access: | https://www.mdpi.com/1660-4601/16/3/356 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yuanyuan Huang Chuancheng Wu Youbin Ye Jingwen Zeng Jianlin Zhu Yuchen Li Wenxiang Wang Wenchang Zhang Yiqin Chen Hongyuan Xie Hongmei Zhang Jin Liu |
spellingShingle |
Yuanyuan Huang Chuancheng Wu Youbin Ye Jingwen Zeng Jianlin Zhu Yuchen Li Wenxiang Wang Wenchang Zhang Yiqin Chen Hongyuan Xie Hongmei Zhang Jin Liu The Increase of ROS Caused by the Interference of DEHP with JNK/p38/p53 Pathway as the Reason for Hepatotoxicity International Journal of Environmental Research and Public Health DEHP ROS JNK/p38MAPK/p53 DNA methylation |
author_facet |
Yuanyuan Huang Chuancheng Wu Youbin Ye Jingwen Zeng Jianlin Zhu Yuchen Li Wenxiang Wang Wenchang Zhang Yiqin Chen Hongyuan Xie Hongmei Zhang Jin Liu |
author_sort |
Yuanyuan Huang |
title |
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_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_sort |
increase of ros caused by the interference of dehp with jnk/p38/p53 pathway as the reason for hepatotoxicity |
publisher |
MDPI AG |
series |
International Journal of Environmental Research and Public Health |
issn |
1660-4601 |
publishDate |
2019-01-01 |
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. |
topic |
DEHP ROS JNK/p38MAPK/p53 DNA methylation |
url |
https://www.mdpi.com/1660-4601/16/3/356 |
work_keys_str_mv |
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doaj-53c42ad71d6840468d0fb1e513be516a2020-11-25T00:27:21ZengMDPI AGInternational Journal of Environmental Research and Public Health1660-46012019-01-0116335610.3390/ijerph16030356ijerph16030356The Increase of ROS Caused by the Interference of DEHP with JNK/p38/p53 Pathway as the Reason for HepatotoxicityYuanyuan Huang0Chuancheng Wu1Youbin Ye2Jingwen Zeng3Jianlin Zhu4Yuchen Li5Wenxiang Wang6Wenchang Zhang7Yiqin Chen8Hongyuan Xie9Hongmei Zhang10Jin Liu11Department of Preventive Medicine, Fujian Provincial Key Laboratory of Environment factors and Cancer, Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Xueyuan Road No.1, Minhou County, Fuzhou 350108, ChinaDepartment of Preventive Medicine, Fujian Provincial Key Laboratory of Environment factors and Cancer, Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Xueyuan Road No.1, Minhou County, Fuzhou 350108, ChinaDepartment of Preventive Medicine, Fujian Provincial Key Laboratory of Environment factors and Cancer, Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Xueyuan Road No.1, Minhou County, Fuzhou 350108, ChinaDepartment of Preventive Medicine, Fujian Provincial Key Laboratory of Environment factors and Cancer, Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Xueyuan Road No.1, Minhou County, Fuzhou 350108, ChinaDepartment of Preventive Medicine, Fujian Provincial Key Laboratory of Environment factors and Cancer, Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Xueyuan Road No.1, Minhou County, Fuzhou 350108, ChinaDepartment of Preventive Medicine, Fujian Provincial Key Laboratory of Environment factors and Cancer, Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Xueyuan Road No.1, Minhou County, Fuzhou 350108, ChinaDepartment of Health Inspection and Quarantine, School of Public Health, Fujian Medical University, Xueyan Road No.1, Minhou County, Fuzhou 350108, ChinaDepartment of Preventive Medicine, Fujian Provincial Key Laboratory of Environment factors and Cancer, Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Xueyuan Road No.1, Minhou County, Fuzhou 350108, ChinaDepartment of Health Inspection and Quarantine, School of Public Health, Fujian Medical University, Xueyan Road No.1, Minhou County, Fuzhou 350108, ChinaDepartment of Preventive Medicine, Fujian Provincial Key Laboratory of Environment factors and Cancer, Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Xueyuan Road No.1, Minhou County, Fuzhou 350108, ChinaDepartment of Preventive Medicine, Fujian Provincial Key Laboratory of Environment factors and Cancer, Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Xueyuan Road No.1, Minhou County, Fuzhou 350108, ChinaDepartment of Preventive Medicine, Fujian Provincial Key Laboratory of Environment factors and Cancer, Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Xueyuan Road No.1, Minhou County, Fuzhou 350108, ChinaAs 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.https://www.mdpi.com/1660-4601/16/3/356DEHPROSJNK/p38MAPK/p53DNA methylation |