Long-term exposure to low-dose di-(2-ethylhexyl) phthalate impairs cholesterol metabolism in hepatic stellate cells and exacerbates liver librosis

Chun Ya Lee, Fat Moon Suk, Yuh Ching Twu, Yi Jen Liao

Research output: Contribution to journalArticle

Abstract

Phthalates are often added to plastic products to increase their flexibility. Di-(2-ethylhexyl) phthalate (DEHP) is one of the most common plasticizers. Previously, a major incident involving phthalate-contaminated foodstuffs occurred, where phthalates were deliberately added to foodstuffs as a substitute for emulsifiers, resulting in a threat to public health. DEHP exposure can cause liver damage and further lead to cancer; however, the effects of long-term exposure to low-dose DEHP on hepatic stellate cells (HSCs) and on liver fibrosis are still unclear. In this study, we showed that chronic exposure to low-dose DEHP results in an accumulation of cholesterol in HSCs by disturbing the cholesterol metabolism and enhancing endogenous cholesterol synthesis. In addition, long-term exposure to low-dose DEHP reduces the sensitivity of HSCs to platelet-derived growth factor BB (PDGF-BB)-induced proliferation by blocking the MAPK pathway. Dysfunction of mitochondrial respiration and induction of caspase 3/PARP-dependent apoptosis were observed in HSCs following chronic, low-dose exposure. The carbon tetrachloride (CCl4)-induced liver fibrosis mouse model showed that long-term administration of DEHP significantly promoted liver damage, inflammatory infiltration, cholesterol accumulation, and deposition of hepatic collagen. In conclusion, long-term exposure to low-dose DEHP may perturb the cholesterol metabolism in HSCs and accelerate liver damage and fibrosis.

Original languageEnglish
Article number3802
JournalInternational journal of environmental research and public health
Volume17
Issue number11
DOIs
Publication statusPublished - Jun 1 2020

Keywords

  • Cholesterol metabolism
  • di-(2-ethylhexyl) phthalate long-term low-dose exposure
  • Hepatic stellate cells
  • Liver fibrosis

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

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