title: A mechanistic study to increase understanding of titanium dioxide nanoparticles-increased plasma glucose in mice.
abstract: Titanium dioxide nanoparticle (TiO2 NP) is an authorized food additive. Previous studies determined oral administration of TiO2 NPs increases plasma glucose in mice via inducing insulin resistance. An increase in reactive oxygen species (ROS) has been considered the possible mechanism of increasing plasma glucose. However, persistently high plasma glucose is also a mechanism of increasing ROS. This study aims to explore whether TiO2 NPs increase plasma glucose via ROS. We found after oral administration of TiO2 NPs, an increase in ROS preceded an increase in plasma glucose. Subsequently, mice were treated with two antioxidants (resveratrol and vitamin E) at the same time as oral administration of TiO2 NPs. Results showed resveratrol and vitamin E reduced TiO2 NPs-increased ROS. An increase in plasma glucose was also inhibited. Further research showed resveratrol and vitamin E inhibited the secretion of TNF-α and IL-6, and the phosphorylation of JNK and p38 MAPK, resulting in improved insulin resistance. These results suggest TiO2 NPs increased ROS levels, and then ROS activated inflammatory cytokines and phosphokinases, and thus induced insulin resistance, resulting in an increase in plasma glucose. Resveratrol and vitamin E can reduce TiO2 NPs-increased ROS and thereby inhibit an increase in plasma glucose in mice.
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Hu
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Guo
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
authors.forename: Sanli
authors.initials: S
authors.lastname: Jin
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Faculty of Education, Wakayama University, Wakayama, Japan.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Oh
authors.affiliation: State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Feng
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.affiliation: School of Life Science and Technology, Harbin Institute of Technology, Harbin, China. Electronic address: guning@hit.edu.cn.
authors.forename: Ning
authors.initials: N
authors.lastname: Gu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis*; D007333:Insulin Resistance; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014025:Titanium / Q000008:administration & dosage / Q000633:toxicity*; D014810:Vitamin E / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D001786:Blood Glucose; D017382:Reactive Oxygen Species; D013267:Stilbenes; D014810:Vitamin E; C009495:titanium dioxide; D014025:Titanium; D000077185:Resveratrol
keywords: Plasma glucose; Reactive oxygen species; Resveratrol; Titanium dioxide nanoparticles; Vitamin E