The Effect of Ingested Titanium Dioxide Nanoparticles on the Course and Prognosis of Ulcerative Colitis in Mice

Abstract

Titanium dioxide (TiO₂), composed of nanoparticles (NPs) and microparticles (MPs), is widely used in food as an additive, which puts consumers suffering the risk of gastrointestinal diseases caused by the invasion of TiO₂ NPs in food products. The purpose of this study was to investigate the effect of TiO₂ NPs on the course and prognosis of ulcerative colitis by gavaging 0, 30, 100, 300 mg/kg TiO₂ NPs during the induction and recovery period of colitis mice induced by 2.5% DSS (dextran sulfate sodium) solution. The results showed that TiO₂ NPs changed the severity of DSS induced colitis, significantly decreasing body weight, obviously increasing DAI and CMDI scores, shortening colonic length, inflammatory infiltration in the colon, and increasing the expression of IL-1β and IL-18. The most obvious change was found in the low dose of TiO₂ NPs during the development of UC and the high dose of TiO₂ NPs during UC self-healing. The changes in ROS levels and T-SOD, GSH-PX and CAT activities indicated that the colitis mice were in a state of oxidative stress, and TiO₂ NP exposure could further trigger the activation of the antioxidant system in colitis mice but did not significantly change the level of oxidative stress. The increase in TXNIP and caspase-1 mRNA expression suggested that TiO₂ NPs might aggravate the development of UC through the ROS-TXNIP-NLRP3 inflammasome pathway. In short, oral intake of TiO₂ NPs could affect the course of acute colitis, exacerbating the development of UC, prolonging the UC course and inhibiting UC recovery.

Note:
Funding Information: This work was supported by the National Natural Science Foundation of China (31971313) and the Beijing Natural Science Foundation (7172116).

Declaration of Interests: The authors declare that they have no known competing financial interests or personal elationships that could have appeared to influence the work reported in this paper

Ethics Approval Statement: The animal experiments were carried out in accordance with the Guiding Principles in the Use of Animals in Toxicology adopted by the Society of Toxicology and received approval from the Peking University Institutional Review Board.

Keywords: titanium dioxide nanoparticles, oxidative stress, inflammatory bowel disease, oral toxicity