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Titanium dioxide nanoparticles increase plasma glucose via reactive oxygen species‐induced insulin resistance in mice
Author(s) -
Hu Hailong,
Guo Qian,
Wang Changlin,
Ma Xiao,
He Hongjuan,
Oh Yuri,
Feng Yujie,
Wu Qiong,
Gu Ning
Publication year - 2015
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.3150
Subject(s) - medicine , endocrinology , insulin resistance , chemistry , reactive oxygen species , insulin , triglyceride , cholesterol , biology , biochemistry
There have been few reports about the possible toxic effects of titanium dioxide (TiO 2 ) nanoparticles on the endocrine system. We explored the endocrine effects of oral administration to mice of anatase TiO 2 nanoparticles (0, 64 and 320 mg kg –1 body weight per day to control, low‐dose and high‐dose groups, respectively, 7 days per week for 14 weeks). TiO 2 nanoparticles were characterized by scanning and transmission electron microscopy (TEM) and dynamic light scattering (DLS), and their physiological distribution was investigated by inductively coupled plasma. Biochemical analyzes included plasma glucose, insulin, heart blood triglycerides (TG), free fatty acid (FFA), low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), total cholesterol (TC), tumor necrosis factor‐alpha (TNF‐α), interleukin (IL)‐6 and reactive oxygen species (ROS)‐related markers (total SOD, GSH and MDA). Phosphorylation of IRS1, Akt, JNK1, and p38 MAPK were analyzed by western blotting. Increased titanium levels were found in the liver, spleen, small intestine, kidney and pancreas. Biochemical analyzes showed that plasma glucose significantly increased whereas there was no difference in plasma insulin secretion. Increased ROS levels were found in serum and the liver, as evidenced by reduced total SOD activity and GSH level and increased MDA content. Western blotting showed that oral administration of TiO 2 nanoparticles induced insulin resistance (IR) in mouse liver, shown by increased phosphorylation of IRS1 (Ser307) and reduced phosphorylation of Akt (Ser473). The pathway by which TiO 2 nanoparticles increase ROS‐induced IR were included in the inflammatory response and phosphokinase, as shown by increased serum levels of TNF‐α and IL‐6 and increased phosphorylation of JNK1 and p38 MAPK in liver. These results show that oral administration of TiO 2 nanoparticles increases ROS, resulting in IR and increasing plasma glucose in mice. Copyright © 2015 John Wiley & Sons, Ltd.