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Environ Toxicol Pharmacol. 2019 May;68:109-119. doi: 10.1016/j.etap.2019.03.008. Epub 2019 Mar 8.

Di(2-ethylhexyl) phthalate promotes hepatic fibrosis by regulation of oxidative stress and inflammation responses in rats.

Author information

1
Institute of Clinical Pharmacology of Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine of Education Ministry, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei, 230032, Anhui, China.
2
Anhui Provincial Hospital, Hefei 230001, Anhui, China. Electronic address: xu_weiping666@163.com.
3
Institute of Clinical Pharmacology of Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine of Education Ministry, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei, 230032, Anhui, China. Electronic address: wwei@ahmu.edu.cn.

Abstract

Di(2-ethylhexyl) phthalate (DEHP) is an environmental pollutant that is widely used in medical and consumer products. An epidemiological study has suggested that a large daily intake of DEHP from phthalate-contaminated food may be a risk factor for liver dysfunction. Long-term exposure to DEHP is associated with liver disease and exacerbates the progression of chronic liver injury. However, the effect of DEHP on hepatic fibrosis is rarely studied. In the present study, we sought to determine the effect of DEHP on carbon tetrachloride (CCl4)-induced liver fibrosis, and to further examine the molecular mechanisms. We found that DEHP exposure remarkably promoted liver inflammation, necrosis and fibrosis, and increased expression of the protein associated with liver inflammation and fibrogenesis, including α-SMA, COL-Ⅰ, COL-Ⅲ, TGF-β1, P-Smad2, P-Smad3, P-p38 and P-p65. The similar trend was observed in the LX-2 cells. Furthermore, DEHP exposure induced oxidative stress and inflammatory cytokine production. Taken together, DEHP might play a fibrotic role in hepatic fibrosis rats and TGF-β1-stimulated LX-2 cells in vitro which was related to TGF-β1/Smad and p38MAPK/NF-κB signal pathway.

KEYWORDS:

DEHP; Hepatic fibrosis; Inflammation; Oxidative stress; TGF-β1; p38MAPK

PMID:
30884453
DOI:
10.1016/j.etap.2019.03.008

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