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.
Department of Health Inspection and Quarantine, School of Public Health, Fujian Medical University, Xueyan Road No.1, Minhou County, Fuzhou 350108, China.
Int J Environ Res Public Health. 2019 Jan 27;16(3):356. doi: 10.3390/ijerph16030356.
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.
作为最常用的增塑剂，邻苯二甲酸二（2-乙基己基）酯（DEHP）由于聚氯乙烯（PVC）在人类生活中的广泛使用而无处不在，它也是一种公认的环境污染物。研究已经证明了 DEHP 的肝毒性，然而其机制尚未得到充分探讨，特别是活性氧（ROS）在其中的作用。在本研究中，将 21 天大的 ICR 小鼠通过灌胃给予 DEHP，剂量分别为 0、125、250 和 375mg/kg/天，共 28 天。污染后，组织病理学显示肝脏组织受到轻度损伤，DEHP 有作用；血清肝功能指标（包括天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT））显著升高。此外，脂质过氧化水平明显升高，特别是 ROS 和丙二醛（MDA），但小鼠肝脏中超氧化物歧化酶（SOD）的活性明显降低。此外，DEHP 促进了小鼠肝脏中 JNK 和 p38MAPK 蛋白的磷酸化，以及 p53 蛋白的表达增加和 p53 基因启动子区域 DNA 甲基化水平的降低。这些结果表明，DEHP 引起的小鼠肝毒性可能是通过激活 JNK/p38MAPK/p53 信号通路，进一步促进 ROS 的产生，诱导肝脏脂质过氧化，而 DNA 甲基化的作用可能是不可避免的。
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