Arabinogalactan ameliorates benzo[a]pyrene-induced intestinal epithelial barrier dysfunction via AhR/MAPK signaling pathway

Abstract

Benzo[a]pyrene (B[a]P), a kind of pollutant, can disrupt the gut microbiota, but its effects on the function of intestinal epithelial barrier (IEB) is still unclear. Arabinogalactan (AG), a natural polysaccharide, can protect intestinal tract. Thus, the purpose of this study was to evaluate the effect of B[a]P on IEB function and the mitigation effect of AG on the IEB dysfunction induced by B[a]P using a Caco-2 cell monolayer model. We found B[a]P could damage the IEB integrity by inducing cell cytotoxicity, increasing lactate dehydrogenase leakage, decreasing the transepithelial electrical resistance, and increasing fluorescein isothiocyanate-dextran flux. The mechanism of B[a]P-induced IEB damage may through induction of oxidative stress, including increasing reactive oxygen species levels, decreasing glutathione levels, reducing the activity of superoxide dismutase, and increasing malonaldehyde levels. Moreover, it can be due to increasing secretion of pro-inflammatory cytokines (interleukin [IL]-1β, IL-6, and tumor necrosis factor [TNF]-α), down-regulated expression of tight junction (TJ) proteins (claudin-1, zonula occludens [ZO]-1, and occludin), and induced activation of aryl hydrocarbon receptor (AhR)/mitogen activated protein kinase (MAPK) signaling pathway. Remarkably, AG ameliorated B[a]P-induced IEB dysfunction through inhibited oxidative stress and pro-inflammatory factor secretion. Our study demonstrated B[a]P could damage the IEB and AG could alleviate this damage.

Keywords: AhR/MAPK signaling pathway; Arabinogalactan; Benzo[a]pyrene; Intestinal epithelium barrier; Oxidative stress.