New insights into quercetin's attenuation of TBBPA-induced injury to MCEC cells: Involvement of the p38/NF-κB pathway and pyroptosis

With the widespread application of the brominated flame retardant tetrabromobisphenol A (TBBPA), it poses a threat to human health, especially intestinal health. Quercetin (Que) is a flavonol compound with anti-inflammatory and antioxidant properties. However, whether Que can prevent TBBPA-induced intestinal toxicity remains unknown. Therefore, in this study, a TBBPA (75 μM) exposure model and a Que (0.1 μM) treatment model were established using mouse colon epithelial cells (MCEC). The p38 pathway, Pyroptosis, and intestinal barrier function-related indicators were analyzed using an oxidative stress reagent kit, immunofluorescence staining, western blotting, and qRT-PCR. The results showed that TBBPA exposure dose-dependently reduced cell viability, impaired the antioxidant function of cells, promoted ROS accumulation, activated the p38 signalling pathway, induced Pyroptosis, and decreased the expression levels of ZO-1, Occludin, and Claudin-1. Notably, Que treatment significantly restored the antioxidant enzyme activity in MCEC cells, reduced the ROS level, inhibited the p38 axis, alleviated MCEC cell Pyroptosis, and recovered the intestinal barrier function. Further studies found that using LX-3 (a p38 activator) treatment disrupted the therapeutic effect of Que. In summary, Que can exert a protective effect by inhibiting the ROS-mediated p38 pathway, thereby alleviating the damage of TBBPA to MCEC cells.

Pyroptosis; Quercetin; Tetrabromobisphenol A; Tight junction; p38/NF-κB.