Arsenic exposure induces intestinal barrier damage and consequent activation of gut-liver axis leading to inflammation and pyroptosis of liver in ducks

Sci Total Environ. 2021 Sep 20:788:147780. doi: 10.1016/j.scitotenv.2021.147780. Epub 2021 May 15.

Abstract

Arsenic is an important hazardous metalloid commonly found in polluted soil, rivers and groundwater. However, few studies exist regarding the effect of arsenic trioxide (ATO) on the gut-liver axis and consequent hepatotoxicity in waterfowl. Here, we investigated the influence of ATO on duck intestines and livers, and explored the role of the gut-liver axis in ATO-induced hepatotoxicity and intestinal toxicity. Our results demonstrated that ATO-exposure induced intestinal damage, liver inflammatory cell infiltration and vesicle steatosis. Additionally, the intestinal microbiota community in ATO-exposed ducks displayed significantly decreased α-diversity and an altered bacterial composition. Moreover, ATO-exposure markedly reduced the expression of intestinal barrier-related proteins (Claudin-1, MUC2, ZO-1 and Occludin), resulting in increased intestinal permeability and elevated lipopolysaccharide levels. Simultaneously, ATO-exposure also upregulated pyroptosis-related index levels in the liver and jejunum, and increased pro-inflammatory cytokine production (IFN-γ, TNF-α, IL-18, and IL-1β). Our further mechanistic studies showed that ATO-induced liver and jejunum inflammation were provoked by the activation of the LPS/TLR4/NF-κB signaling pathway and NLRP3 inflammasome. In summary, these results manifested that ATO exposure can cause liver and jejunal inflammation and pyroptosis, and the indirect gut-liver axis pathway may play an essential role in the potential mechanism of ATO-induced hepatotoxicity.

Keywords: Arsenic; Duck; Gut-liver axis; Intestinal microbiota; Pyroptosis.

MeSH terms

  • Animals
  • Arsenic* / toxicity
  • Ducks*
  • Inflammation / chemically induced
  • Liver
  • Pyroptosis

Substances

  • Arsenic