A single or short time repeated arsenic oral exposure in mice impacts mRNA expression for signaling and immunity related genes in the gut

Food Chem Toxicol. 2019 Oct:132:110597. doi: 10.1016/j.fct.2019.110597. Epub 2019 Jun 21.

Abstract

Arsenic is prevalent in contaminated drinking water and affects more than 140 million people in 50 countries. While the wide-ranging effects of arsenic on neurological development and cancer draw the majority of concern, arsenic's effects on the gut mucosa-associated immune system are often overlooked. In this study, we show that 24 h after a single dose [low dose (50 μg/kg bw), medium dose (100 μg/kg bw) or high dose (200 μg/kg bw)] of arsenic by oral gavage, mice show significantly reduced gut mucosa-associated mRNA expression for the key genes involved in the signaling pathways central to immune responses, such as Nuclear factor κB (NFκB), Extracellular signal-regulated protein kinases 1 and 2 (ERK1/2), p38 and Myeloid differentiation protein 88-dependent (Myd88) pathways. Additionally, mRNA expression of apoptosis, inflammasomes and inflammatory response genes are significantly downregulated in the animals exposed to arsenic. Comparisons of time-dependent effects (24 h vs 48 h) from low dose arsenic exposed animals showed a significant shift in expression of Myd88 alone, suggesting that the down regulation was sustained for the key genes/signaling pathway. An extended eight-day exposure to arsenic showed a decreased state of immune preparedness, though not as diminished as seen in the single dose exposure.

Keywords: Apoptosis; Arsenic; Immune response; Inflammasome; Inflammation; Inflammatory response; mRNA expression.

MeSH terms

  • Administration, Oral
  • Animals
  • Arsenic / administration & dosage
  • Arsenic / adverse effects*
  • Down-Regulation
  • Female
  • Immune System / drug effects*
  • Inflammasomes / genetics
  • Intestines / drug effects*
  • Intestines / immunology
  • MAP Kinase Signaling System / drug effects*
  • MAP Kinase Signaling System / genetics
  • Mice
  • Myeloid Differentiation Factor 88 / genetics
  • NF-kappa B / genetics
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Time Factors
  • Water Pollutants, Chemical / administration & dosage
  • Water Pollutants, Chemical / adverse effects*

Substances

  • Inflammasomes
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • RNA, Messenger
  • Water Pollutants, Chemical
  • Arsenic