Gastrointestinal dysfunction as the main performance of the oral toxicity of titanium dioxide nanoparticle on gastric ulcer rats

Titanium dioxide nanoparticles (TiO 2 NPs) have promising applications in food additives and pharmaceutical dressings, raising concerns about their oral safety. The current studies mainly focus on healthy groups, and the effect of TiO 2 NPs on the patient population is rarely known. Here, a comprehensive toxicity study of TiO 2 NPs (75 ± 15 nm, anatase) in gastric ulcer rats ( male 8-week old Sprague-Dawley rats) is reported following oral exposure at dose of 0, 10, 50, 200 mg/kg body weight per day for 30 days. The gastric ulcer rats were produced by submucosal injection of acetic acid solution into the rat stomach. The healthy rats were used as the normal control. We evaluated nanoparticle biodistribution, systemic toxicity, and gastrointestinal function indices in the rats. Our findings indicate that oral administration of TiO 2 NPs resulted in minimal intestinal absorption and transport with limited systemic organ toxicity. The internalization of TiO2 NPs and activation of mast cells in the stomach tissues, along with the low serum levels of histamine and IgE, suggest a localized allergic reaction rather than a systemic one. Furthermore, the notably reduced plasma levels of D-lactate and the activity of diamine oxidase (DAO) indicated the upregulation of intestinal barrier function. These statistically significant results indicated that gastrointestinal dysfunction was the main performance of the oral toxicity of TiO 2 NPs on gastric ulcer rats, emphasizing the importance of controlling the intake of TiO 2 NPs in patients with gastric ulcers.