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

Yuanyuan Huang, Chuancheng Wu, Youbin Ye, Jingwen Zeng, Jianlin Zhu, Yuchen Li, Wenxiang Wang, Wenchang Zhang, Yiqin Chen, Hongyuan Xie, Hongmei Zhang and Jin Liu
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Yuanyuan Huang: Department 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, China
Chuancheng Wu: Department 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, China
Youbin Ye: Department 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, China
Jingwen Zeng: Department 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, China
Jianlin Zhu: Department 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, China
Yuchen Li: Department 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, China
Wenxiang Wang: Department of Health Inspection and Quarantine, School of Public Health, Fujian Medical University, Xueyan Road No.1, Minhou County, Fuzhou 350108, China
Wenchang Zhang: Department 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, China
Yiqin Chen: Department of Health Inspection and Quarantine, School of Public Health, Fujian Medical University, Xueyan Road No.1, Minhou County, Fuzhou 350108, China
Hongyuan Xie: Department 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, China
Hongmei Zhang: Department 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, China
Jin Liu: Department 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, China

IJERPH, 2019, vol. 16, issue 3, 1-14

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.

Keywords: DEHP; ROS; JNK/p38MAPK/p53; DNA methylation (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2019
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