DEHP triggers a damage severity grade increase in the jejunum in quail (Coturnix japonica) by disturbing nuclear xenobiotic receptors and the Nrf2-mediated defense response

Environ Toxicol Pharmacol. 2022 Nov:96:104012. doi: 10.1016/j.etap.2022.104012. Epub 2022 Nov 11.

Abstract

As a plasticizer, di-2-ethylhexyl phthalate (DEHP) has been listed as a potential endocrine disruptor by The World Health Organization. The toxicity of DEHP has been widely studied, but its toxicity on the digestive tract of birds has not been clarified. Female quail were treated by gavage with DEHP (250, 500, 750 mg/kg), with the blank and vehicle control groups reserved. The result showed that DEHP raised the damage severity grade, and decreased the ratio of villus length to crypt depth. The content and activity of cytochrome P450 system (CYP450s) were increased by DEHP. DEHP interfered with the transcription of nuclear xenobiotic receptors (NXRs), CYP isoforms, and the nuclear factor-E2-related factor 2 (Nrf2) signaling pathway. This study revealed DEHP could cause the imbalance in CYP450s mediated by NXRs, and then promote Nrf2 mediated antioxidant defense. This study provided new evidence about the mechanisms of DEHP-induced toxic effects on digestive tract.

Keywords: Cytochrome P450; Di-2-ethylhexyl phthalate; Jejunum; Nrf2 signaling pathway; Nuclear xenobiotic receptors.

MeSH terms

  • Animals
  • Coturnix* / metabolism
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • Diethylhexyl Phthalate* / toxicity
  • Female
  • Jejunum / metabolism
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Quail / metabolism
  • Receptors, Cytoplasmic and Nuclear
  • Xenobiotics

Substances

  • NF-E2-Related Factor 2
  • Diethylhexyl Phthalate
  • Xenobiotics
  • Receptors, Cytoplasmic and Nuclear
  • Cytochrome P-450 Enzyme System