Effects of sunset yellow on proliferation and differentiation of intestinal epithelial cells in murine intestinal organoids

J Appl Toxicol. 2021 Jun;41(6):953-963. doi: 10.1002/jat.4080. Epub 2020 Oct 15.

Abstract

Sunset yellow (SY), an azo dye, is commonly used in the food industry. The scientific literature contains little information regarding the effects of SY on small intestinal epithelial cells (IECs). In this study, a small intestinal organoid model was used in in vitro toxicological studies of SY, and intestinal inflammatory responses in vivo to SY were investigated with the dextran sulfate sodium (DSS)-induced intestinal inflammation model in C57BL/6 mice. The intestinal organoids were cultured with 2 μg/ml SY for two generations, the growth rates were analyzed, and the expressions of cell lineages were assayed. For inflammatory responses, mice were fed with a diet containing 40 mg/kg diet SY and treated with 2.5% DSS for 7 days. The results showed that SY inhibited the growth of the organoids by inhibiting the proliferation and disturbing the differentiation of IECs. Furthermore, endoplasmic reticulum (ER) stress and oxidative stress levels were elevated in SY-treated organoids. In DSS-treated mice, the disease activity index and expression levels of interleukin-1β and tumor necrosis factor-α were enhanced in the SY group, concluding that SY exacerbated DSS-induced intestinal inflammation. Taken together, these findings revealed that SY could disturb the homeostasis of the small intestinal epithelium by generating high levels of ER stress and oxidative stress, with long-term continuous consumption of SY potentially increasing the risk of intestinal inflammation.

Keywords: endoplasmic reticulum stress; inflammation; organoid; proliferation; sunset yellow.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azo Compounds / pharmacology
  • Azo Compounds / toxicity*
  • Cell Differentiation / drug effects*
  • Cell Proliferation
  • Endoplasmic Reticulum Stress / drug effects
  • Epithelial Cells / drug effects*
  • Interleukin-1beta
  • Intestinal Mucosa / drug effects
  • Intestine, Small / metabolism
  • Intestines
  • Mice
  • Mice, Inbred C57BL
  • Organoids / physiology*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Azo Compounds
  • IL1B protein, human
  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • 6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt