Abstract
Bisphenol A (BPA), a globally prevalent environmental contaminant, has been shown to have the potential to disrupt intestinal barrier function. This study explored the mechanisms of BPA-induced intestinal barrier dysfunction. In addition, the protective effect of the natural product icariin (ICA) on BPA-induced intestinal barrier dysfunction was evaluated. BPA relieved oxidative stress (reactive oxygen species (ROS), reactive nitrogen species (RNS), malondialdehyde (MDA), and hydrogen peroxide (H2O2)), suppressed antioxidant enzyme (superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and total antioxidant capacity (T-AOC)) activity, and increased gene expression and protein content of p38 mitogen-activated protein kinase (MAPK), giving rise to the dysfunctional gut in mice. ICA therapy effectively eased intestinal barrier dysfunction caused by BPA in vivo and in vitro. Treatment with p38 MAPK inhibitor (SB203580) significantly rescued the MODE-K cell barrier function disrupted by BPA challenge. However, treatment with p38 MAPK activator (anisomycin) did not attenuate the MODE-K cell barrier function impaired by BPA challenge. Overall, our data suggested that BPA disrupted intestinal barrier function in a p38 MAPK-dependent manner. Furthermore, we demonstrated that ICA regulated the redox equilibrium of intestinal epithelial cells by inhibiting the expression of p38 MAPK, thereby alleviating BPA-induced disruption of intestinal barrier function. These findings contributed to a better understanding of the mechanisms of BPA-induced intestinal barrier dysfunction and provided new insights into the prevention and treatment of BPA-induced intestinal diseases.