Di (2-ethylhexyl) phthalate (DEHP)-induced hepatotoxicity in quails (Coturnix japonica) via triggering nuclear xenobiotic receptors and modulating cytochrome P450 systems

Food Chem Toxicol. 2018 Oct:120:287-293. doi: 10.1016/j.fct.2018.07.019. Epub 2018 Jul 11.

Abstract

Di (2-ethylhexyl) phthalate (DEHP) is a widely distributed pollutant that is of great concern due to its negative health effects. However, whether DEHP exposure causes liver toxicity in birds remains unclear. To clarify the potential hepatotoxicity of DEHP, quails were exposed to 0, 250, 500 and 1000 mg/kg BW/day DEHP by gavage treatment for 45 days. The livers of DEHP-exposed quails showed histomorphological changes. DEHP exposure induced a significant increase in cytochrome P450 enzyme system (CYP450s) activity (including aniline-4-hydroxylase (AH), aminopyrine N-demethylase (APND), erythromycin N-demethylase (ERND) and NADPH-cytochrome C reductase (NCR)) and in the contents of total cytochrome P450 (CYP450) and cytochrome b5 (Cyt b5) in quail liver. DEHP exposure also influenced the expression of nuclear xenobiotic receptors (NXRs) and CYP450 isoforms in the liver. The results suggested that DEHP-induced hepatotoxicity in quail liver is associated with activation of the NXRs pathway responses and disruption of CYP450s homeostasis. This study will help to further elucidate DEHP exposure-induced liver toxicity in quails.

Keywords: Cytochrome P450; DEHP; Liver microsome; NXRs response; Quails.

MeSH terms

  • Animals
  • Coturnix
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism*
  • Diethylhexyl Phthalate / toxicity*
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects
  • Homeostasis / drug effects
  • Liver / drug effects*
  • Liver / enzymology
  • Liver / pathology
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology
  • RNA, Messenger / metabolism
  • Real-Time Polymerase Chain Reaction
  • Receptors, Cytoplasmic and Nuclear / drug effects*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Transcription, Genetic / drug effects
  • Xenobiotics / toxicity*

Substances

  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Xenobiotics
  • Cytochrome P-450 Enzyme System
  • Diethylhexyl Phthalate