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

Overview

Journal Int J Environ Res Public Health

Publisher MDPI

Specialties Environmental Health
Public Health

Date 2019 Jan 30

PMID 30691201

Citations 14

Authors

Yuanyuan Huang

Chuancheng Wu

Youbin Ye

Jingwen Zeng

Jianlin Zhu

Yuchen Li

Wenxiang Wang

Wenchang Zhang

Yiqin Chen

Hongyuan Xie

Hongmei Zhang

Jin Liu

Affiliations

Soon will be listed here.

Abstract

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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