Food emulsifier polysorbate 80 promotes the intestinal absorption of mono-2-ethylhexyl phthalate by disturbing intestinal barrier

Toxicol Appl Pharmacol. 2021 Mar 1:414:115411. doi: 10.1016/j.taap.2021.115411. Epub 2021 Jan 18.

Abstract

Di-2-ethylhexyl phosphate (DEHP) and its main toxic metabolite mono-2-ethylhexyl phthalate (MEHP) are the typical endocrine disrupting chemicals (EDCs) and widely affect human health. Our previous research reported that synthetic nonionic dietary emulsifier polysorbate 80 (P80, E433) had the promotional effect on the oral absorption of DEHP in rats. The aim of this study was to explore its mechanism of promoting oral absorption, focusing on the mucus barrier and mucosal barrier of the small intestine. A small molecule fluorescent probe 5-aminofluorescein-MEHP (MEHP-AF) was used as a tracker of MEHP in vivo and in vitro. First of all, we verified that P80 promoted the bioavailability of MEHP-AF in the long-term and low-dose exposure of MEHP-AF with P80 as a result of increasing the intestinal absorption of MEHP-AF. Afterwards, experimental results from Western blot, qPCR, immunohistochemistry, and immunofluorescence showed that P80 decreased the expression of proteins (mucus protein mucin-2, tight junction proteins claudin-1 and occludin) related to mucus barrier and mucosal barrier in the intestine, changed the integrity of intestinal epithelial cell, and increased the permeability of intestinal epithelial mucosa. These results indicated that P80 promoted the oral absorption of MEHP-AF by altering the intestinal mucus barrier and mucosal barrier. These findings are of great importance for assessing the safety risks of some food emulsifiers and clarifying the absorption mechanism of chemical pollutants in food, especially for EDCs.

Keywords: Emulsifier; Intestinal absorption; Intestinal mucosa barrier; Intestinal mucus barrier; MEHP; Plasticizers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Availability
  • Caco-2 Cells
  • Claudin-1 / metabolism
  • Diethylhexyl Phthalate / analogs & derivatives*
  • Diethylhexyl Phthalate / pharmacokinetics
  • Diethylhexyl Phthalate / toxicity
  • Emulsifying Agents / toxicity*
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Fluoresceins / metabolism
  • Fluorescent Dyes / metabolism
  • HT29 Cells
  • Humans
  • Intestinal Absorption / drug effects*
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Intestine, Small / drug effects*
  • Intestine, Small / metabolism
  • Male
  • Mice
  • Mice, Inbred ICR
  • Mucin-2 / metabolism
  • Occludin / metabolism
  • Permeability
  • Polysorbates / toxicity*
  • Rats
  • Rats, Sprague-Dawley
  • Tissue Distribution
  • Toxicokinetics

Substances

  • Claudin-1
  • Emulsifying Agents
  • Fluoresceins
  • Fluorescent Dyes
  • Mucin-2
  • Occludin
  • Polysorbates
  • 5-aminofluorescein
  • Diethylhexyl Phthalate
  • mono-(2-ethylhexyl)phthalate