Oxidative Damage and Nrf2 Translocation Induced by Toxicities of Deoxynivalenol on the Placental and Embryo on Gestation Day 12.5 d and 18.5 d

Toxins (Basel). 2018 Sep 13;10(9):370. doi: 10.3390/toxins10090370.

Abstract

Deoxynivalenol (DON) is a kind of natural pollutant belonging to the trichothecenes family. The aim of this study is to use diverse assays to evaluate oxidative damage as well as translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), and to investigate their mechanisms in DON-induced toxicities on a placenta and embryo. Pregnant C57BL/6 mice were randomly assigned to three groups with different doses of DON: 0, 1.0, 2.5 mg/(kg·day). In gestation day (GD) 12.5 d and 18.5 d, DON induced an elevated resorption rate of the embryos as well as structural and functional damage of the placenta. In the placenta, altered levels of the antioxidant enzymes malondialdehyde, superoxide dismutase and glutathione indicated remarkable oxidative stress. Furthermore, an elevated level of heme oxygenase-1 (HO-1) and the translocation of Nrf2 from nucleus to cytoplasm indicated Nrf2/HO-1 pathway activation in DON-L group (1.0 mg/(kg·day)). It is noteworthy that the results in this experiment in GD 12.5 d were similar to those in GD 18.5 d. In conclusion, DON-induced placental oxidative damage and Nrf2 translocation were similar in GD 12.5 d and GD 18.5 d. Oxidative stress is one of the most important molecular mechanisms for embryotoxicity induced by DON, and Nrf2 translocation may play a substantial role against it.

Keywords: Nrf2 translocation; deoxynivalenol (DON); embryotoxicity; placenta.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Embryo, Mammalian / drug effects*
  • Embryo, Mammalian / metabolism
  • Female
  • Glutathione / metabolism
  • Heme Oxygenase-1 / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Membrane Proteins / metabolism
  • Mice, Inbred C57BL
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress / drug effects
  • Placenta / drug effects*
  • Placenta / metabolism
  • Pregnancy
  • Superoxide Dismutase / metabolism
  • Trichothecenes / toxicity*

Substances

  • Membrane Proteins
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Trichothecenes
  • Malondialdehyde
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • Superoxide Dismutase
  • Glutathione
  • deoxynivalenol