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The effects of di 2-ethyl hexyl phthalate (DEHP) on cellular lipid accumulation in HepG2 cells and its potential mechanisms in the molecular level
Authors:Wang Zhang  Xin-Yue Shen  Wen-Wen Zhang  Hao Chen  Wei-Ping Xu
Affiliation:1. Key Laboratory of Anti-inflammatory and Immune Medicine of Education Ministry, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Institute of Clinical Pharmacology of Anhui Medical University, Hefei, Anhui, China;2. Affiliated Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui, China
Abstract:Diethylhexyl phthalate (DEHP) is suspected to be an inevitable factor related to metabolic disease. Our previous study demonstrated that excess DEHP could exacerbate non-alcoholic fatty liver disease (NAFLD) in SD rats. Addressing the terra incognita in DEHP-induced metabolic dysfunction, this study used HepG2 cells to investigate the potential mechanisms involved in DEHP-induced toxicity in vitro. The cells were established lipid overload model with oleic acid and BSA, then exposed to different concentrations (5, 10, 25, 50, 100?μmol/l DEHP) of DEHP for further analysis. The Oil Red O staining results showed that DEHP could promote lipid accumulation in cells. The level of superoxide dismutase (SOD) and malondialdehyde (MDA) changed suggested the balance of oxidative stress was disrupted. Additionally, western blot analysis showed that DEHP could promote the expression of peroxisome proliferator-activated receptor α (PPARα) and sterol regulatory element-binding protein 1c (SREBP-1c). By quantifying the expressions of the two proteins, it is of interest to determine that DEHP could promote lipid accumulation in hepatocytes via activating the SREBP-1c and PPARα-signaling pathway.
Keywords:DEHP  lipid accumulation  PPAR  SREBP  ROS
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