Foodborne Titanium Dioxide Nanoparticles Aggravated Secondary Liver Injury in DSS-Induced Colitis: Role of the NLRP3 Inflammasome.

Abstract

Secondary liver injury (SLI) is the most common complication in the development of inflammatory bowel disease (IBD), and it is susceptible to environmental factors, including diet patterns. As a food-brightening agent, titanium dioxide nanoparticles (TiO₂ NPs) are inevitably consumed by IBD patients. Currently, there are a few studies on TiO₂ NPs exposure to SLI in colitis mice. In this study, a SLI model was built using dextran sodium sulfate (DSS) free-drinking for 7 days after pre-exposure to TiO₂ NPs. The changes in the pathological results and liver function indicators suggested that high-dose TiO₂ NPs only exhibited a slight injury in the liver. With further analysis, we found that pre-exposure to high-dose TiO₂ NPs in mice with SLI led to an increase in intestinal permeability and hepatic LPS content, along with increased inflammatory cytokines and an anti-oxidative system imbalance. Subsequently, accumulated LPS and ROS overproduction activated the NOD-like receptor family pyrin-containing 3 (NLRP3) inflammasome, inducing hepatic cell pyroptosis. To provide compelling evidence, NLRP3 gene-deficient mice were used, and the results showed that the absence of NLRP3 improved liver function, alleviated hepatic inflammation, and reduced hepatic oxidative injury in SLI mice with TiO₂ NPs exposure. In summary, these results confirmed the critical role of the NLRP3 inflammasome in the TiO₂ NP-aggravated progression of SLI. Our study provided a comprehensive evaluation of foodborne nanoparticles on IBD complications, hoping that more studies can focus on IBD complications affected by environmental factors.