In vivo evaluation of the effect of arsenite on the intestinal epithelium and associated microbiota in mice

Arch Toxicol. 2019 Aug;93(8):2127-2139. doi: 10.1007/s00204-019-02510-w. Epub 2019 Jul 15.


Chronic exposure to inorganic arsenic (As) [As(III) + As(V)], which affects millions of people, increases the incidence of some kinds of cancer and other non-carcinogenic pathologies. Although the oral pathway is the main form of exposure, in vivo studies have not been conducted to verify the intestinal toxicity of this metalloid. The aim of this study is to perform an in vivo evaluation of the intestinal toxicity of inorganic As, using female BALB/c mice exposed through drinking water to various concentrations of As(III) (20, 50, and 80 mg/L) for 2 months. An increase was observed in oxygen and/or nitrogen reactive species, and in gene and protein expression of pro-inflammatory cytokines (IL-1β, IL-2, IL-6) at concentrations equal to or greater than 50 mg/L. These changes were accompanied by a profound remodeling of the intestinal microbial profile in terms of diversity and global composition, which could be at the basis or exacerbate As(III) toxic effects. The histological study showed that there was moderate inflammation of the mucosa and submucosa, accompanied by hyperplasia of crypts at the highest administered dose. In addition, all the treatments with As(III) resulted in a decreased expression of Muc2, which encodes one of the main components of the intestinal layer of mucus. The effects described are compatible with the increased intestinal permeability observed at concentrations equal to or greater than 50 mg/L, indicative of loss of barrier function.

Keywords: Arsenite; Intestinal epithelium; Intestinal permeability; Microbiota.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arsenites / administration & dosage
  • Arsenites / toxicity*
  • Cytokines / genetics
  • Female
  • Gastroenteritis / chemically induced
  • Gastroenteritis / metabolism
  • Gastroenteritis / pathology
  • Gastrointestinal Microbiome / drug effects*
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / pathology*
  • Mice, Inbred BALB C
  • Mucin-2 / genetics
  • Oxidative Stress / drug effects
  • Reactive Oxygen Species / metabolism
  • Tight Junction Proteins / genetics
  • Tight Junction Proteins / metabolism
  • Toxicity Tests, Subchronic


  • Arsenites
  • Cytokines
  • Muc2 protein, mouse
  • Mucin-2
  • Reactive Oxygen Species
  • Tight Junction Proteins
  • arsenite