Di(2-ethylhexyl) phthalate disturbs cholesterol metabolism through oxidative stress in rat liver

Environ Toxicol Pharmacol. 2022 Oct;95:103958. doi: 10.1016/j.etap.2022.103958. Epub 2022 Aug 13.


Di(2-ethylhexyl) phthalate (DEHP) is widely used and has been implicated in hepatotoxicity, although the mechanism is unclear. Here, we investigated the effect of DEHP on hepatic cholesterol metabolism in SD rats exposed to 0 and 300 mg/kg/day DEHP for 12 weeks. An RNA-Seq analysis was performed to describe the hepatic responses to long-term DEHP exposure in combination with serological and oxidative stress parameter measurements. DEHP increased the serum levels of total cholesterol (TC), high-density lipoprotein (HDL), and alanine transaminase (ALT). Moreover, DEHP increased the content of malondialdehyde (MDA) and decreased antioxidant enzyme activities in the liver. Transcriptomic results revealed that DEHP dramatically changed the cholesterol metabolism pathway and oxidation-reduction process and depressed gene expression involved in cholesterol efflux and monooxygenase activity. Total antioxidant capacity (T-AOC) positively correlated with Abcg5 and Abcg8. Overall, this study showed the mechanisms underlying hepatotoxicity caused by DEHP, providing new insights into understanding DEHP poisoning.

Keywords: Cholesterol metabolism; DEHP; Hepatotoxicity; Oxidative stress; Transcriptomics.

MeSH terms

  • Alanine Transaminase / metabolism
  • Animals
  • Antioxidants / pharmacology
  • Chemical and Drug Induced Liver Injury* / metabolism
  • Cholesterol
  • Diethylhexyl Phthalate* / toxicity
  • Lipoproteins, HDL / metabolism
  • Liver
  • Malondialdehyde / metabolism
  • Mixed Function Oxygenases / metabolism
  • Oxidative Stress
  • Phthalic Acids
  • Rats
  • Rats, Sprague-Dawley


  • Antioxidants
  • Lipoproteins, HDL
  • Phthalic Acids
  • Malondialdehyde
  • phthalic acid
  • Cholesterol
  • Diethylhexyl Phthalate
  • Mixed Function Oxygenases
  • Alanine Transaminase