期刊
ENVIRONMENTAL TOXICOLOGY
卷 34, 期 11, 页码 1221-1235出版社
WILEY
DOI: 10.1002/tox.22823
关键词
endoplasmic reticulum stress; mice; plasma glucose; reactive oxygen species; titanium dioxide nanoparticles
资金
- Fundamental Research Funds for the Central Universities [HIT. NSRIF. 201669]
- National Funds for Creative Research Group of China [51121062]
- National Natural Science Foundation of China [21677044]
- Open Project of State Key Laboratory of Urban Water Resource and Environment of Harbin Institute of Technology [HCK201805]
Titanium dioxide nanoparticles (TiO2 NPs) are reported to increase plasma glucose levels in mice at specific doses. The production and accumulation of reactive oxygen species (ROS) is potentially the most important factor underlying the biological toxicity of TiO2 NPs but the underlying mechanisms are unclear at present. Data from genome-wide analyses showed that TiO2 NPs induce endoplasmic reticulum (ER) stress and ROS generation, leading to the inference that TiO2 NP-induced ER stress contributes to enhancement of ROS in mice. Resveratrol (Res) effectively relieved TiO2 NP-induced ER stress and ROS generation by ameliorating expression of a common set of activated genes for both processes, signifying that ER stress and ROS are closely related. TiO2 NP-induced ER stress occurred earlier than ROS generation. Upon treatment with 4-phenylbutyric acid to relieve ER stress, plasma glucose levels tended toward normal and TiO2 NP increased ROS production was inhibited. These results suggest that TiO2 NP-induced ER stress promotes the generation of ROS, in turn, triggering increased plasma glucose levels in mice. In addition, Res that displays the ability to reduce ER stress presents a dietary polyphenol antioxidant that can effectively prevent the toxicological effects of TiO2 NPs on plasma glucose metabolism.
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