Potential mitigation of titanium dioxide nanoparticles against 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis through inhibiting the canonical NF-κB pathway

Titanium dioxide nanoparticles (TiO₂ NPs) have been widely employed in various industry fields, which makes consumers concerned about their health impact. Our previous work displayed that TiO₂ NPs participated in the mitigation of TNBS-induced colitis, but the mechanism is still unknown. This work aimed to explore the role of oxidative stress and NF-κB pathway in the effect of TiO₂ NPs on TNBS-induced colitis. The results showed that TiO₂ NPs administration reduced the DAI score of colitis mice after TNBS enema. TiO₂ NPs did not alter oxidative stress status (GSH/GSSG), but repaired the gut dysbacteriosis and inhibited the canonical NF-κB pathway activation in TNBS-induced colitis mice, manifested as a decrease in pathogenic bacteria and an increase in beneficial bacteria, as well as down-regulation of toll-like receptors (TLRs), IKKα, IKKβ, p65 and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α and IFN-γ) in mRNA level, and the increased transcription of anti-inflammatory cytokines (IL-10, TGF-β, and IL-12), along with the declined protein level of TNF-α in TiO₂ NPs treated colitis mice. The present study suggested that oral TiO₂ NPs administration inhibited the canonical NF-κB pathway activation by repairing gut dysbacteriosis, which made a predominant role in alleviating colitis. These findings provided a new perspective for exploring the safety of TiO₂ NPs.