Effect of Subchronic Exposure to Inorganic Arsenic on the Structure and Function of the Intestinal Epithelium

Toxicol Lett. 2018 Apr;286:80-88. doi: 10.1016/j.toxlet.2018.01.011. Epub 2018 Jan 31.

Abstract

Inorganic arsenic (As), the most toxic form of As found in water and food, is considered a human carcinogen. Numerous studies show its systemic toxicity, describing pathologies associated with chronic exposure. The main pathway of exposure to inorganic As is oral, but many of the events that occur during its passage through the gastrointestinal tract are unknown. This study evaluates the effect of subchronic exposure to inorganic As [As(III): 0.025-0.1 mg/L; As(V): 0.25-1 mg/L, up to 21 days] on the intestinal epithelium, using Caco-2 cells as in vitro model. Inorganic As produces a pro-inflammatory response throughout the exposure time, with an increase in IL-8 release (up to 488%). It also causes changes in the program of cell proliferation and differentiation, which leads to impairment of the cell repair process. In addition, subchronic exposure affects the epithelial structure, causing loss of microvilli, fundamental structures in the processes of intestinal absorption and digestion. Moreover, the exposure affects the epithelial barrier function, evidenced by an increase of Lucifer Yellow transport (103-199%). Therefore, it can be concluded that subchronic exposure to inorganic As can alter intestinal homeostasis, affecting the mucosal layer, which performs the most important functions of the intestinal wall.

Keywords: Caco-2 cells; Differentiation; Inflammation; Inorganic arsenic; Intestinal epithelium; Permeability; Proliferation; Subchronic exposure; Wound healing.

MeSH terms

  • Arsenic Trioxide
  • Arsenicals
  • Caco-2 Cells
  • Cell Differentiation / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Digestion / drug effects
  • Dose-Response Relationship, Drug
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Epithelial Cells / ultrastructure
  • Gene Expression Regulation / drug effects
  • Humans
  • Inflammation Mediators / metabolism
  • Interleukin-8 / metabolism
  • Intestinal Absorption / drug effects
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / ultrastructure
  • Microvilli / drug effects
  • Microvilli / metabolism
  • Microvilli / ultrastructure
  • Oxides / toxicity*
  • Permeability
  • Risk Assessment
  • Time Factors
  • Toxicity Tests, Subchronic
  • Up-Regulation
  • Wound Healing / drug effects

Substances

  • Arsenicals
  • CXCL8 protein, human
  • Inflammation Mediators
  • Interleukin-8
  • Oxides
  • Arsenic Trioxide