Molecular mechanism of mice gastric oxidative damage induced by nanoparticulate titanium dioxide

Jianhui Ji; Yingjun Zhou; Fashui Hong; Yuguan Ze; Dongxue Fan; Xingxiang Zhang

doi:10.1093/toxres/tfaa086

Molecular mechanism of mice gastric oxidative damage induced by nanoparticulate titanium dioxide

Toxicol Res (Camb). 2021 Jan 5;10(1):60-67. doi: 10.1093/toxres/tfaa086. eCollection 2021 Jan.

Authors

Jianhui Ji¹, Yingjun Zhou¹, Fashui Hong¹, Yuguan Ze², Dongxue Fan¹, Xingxiang Zhang¹

Affiliations

¹ Jiangsu Collaborative Innovation Center of Regional Modern Agriculture & Environmental Protection, Huaiyin Normal University, Huai'an 223300, China.
² School of Basic Medicine and Biological Sciences of Soochow University, Suzhou 215123, China.

Abstract

Background: Nanoparticulate titanium dioxide (Nano-TiO₂) has been widely used in food industry, and it has been demonstrated to have adverse effects on mice and human stomach, but its mechanism is rarely concerned. The aim of this study is to determine the effects of nano-TiO₂ on the stomach and confirm the role of oxidative stress and apoptosis in the mice gastric damage caused by nano-TiO₂, as well as its molecular mechanisms.

Methods: Mice were continuously exposed to nano-TiO₂ with 1.25, 2.5 and 5 mg/kg bw by intragastric administration for 9 months in the present study. The ultrastructure, levels of reactive oxygen species (ROS) and peroxides, activities of antioxidant enzymes and mitochondria-related enzymes, ATP contents as well as apoptosis-related factors expression in mice stomach were examined.

Results: Oxidative stress, apoptosis and nano-TiO₂ aggregation were found in gastric mucosal smooth muscle cells after nano-TiO₂ exposure. Nano-TiO₂ exposure also resulted in the over-production of ROS and peroxides, decrease of ATP production and activities of antioxidant enzymes and mitochondria-related ATPases, upregulation of apoptosis-related factors including γH2AX, Cyt c, caspase 3, and p-JNK expression, and down-regulation of Bcl-2 expression in mice stomach.

Conclusions: The gastric toxicity of mice induced by chronic exposure to low dose nano-TiO₂ may be associated with oxidative stress and mitochondria-mediated apoptosis in mice.

Keywords: Nanoparticulate titanium dioxide; gastric damage; oxidative stress; stomach.