Regulatory effects of flavonoids luteolin on BDE-209-induced intestinal epithelial barrier damage in Caco-2 cell monolayer model

Abstract

Polybrominated diphenyl ethers (PBDEs) are persistent organic pollutants (POPs). They are constantly detected in foods. PBDEs can disrupt the intestinal flora, but enterotoxicity is unknown. Luteolin, one kind of flavonoid, has drawn increasing interest as an agent that strengthens the intestinal barrier. This study aimed to evaluate the mitigating effect of luteolin on damage to the intestinal barrier induced by decabromodiphenyl ether (BDE-209) in a Caco-2 cell monolayer model. Results showed that luteolin mitigated BDE-209-induced damage to intestinal epithelial barrier by reducing the levels of reactive oxygen species (ROS), increasing the activity of superoxide dismutase (SOD) and glutathione (GSH), suppressed the secretion of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), and increased the expression of tight junction (TJ) proteins (ZO-1, occludin, and claudin-1). Furthermore, the protective effects were related to the inhibition of extracellular regulated protein kinases (ERK) and nuclear factor kappa-B (NF-κB)/myosin light chain kinase (MLCK) signaling pathways, and the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways. This study is the first to provide strong evidence that BDE-209 can damage the intestinal barrier, and we here investigated the important protective effect of luteolin, which may lay the foundation for the development of luteolin as a dietary supplement to strengthen the intestinal barrier.