title: Oral administration of nano-titanium dioxide particle disrupts hepatic metabolic functions in a mouse model.
abstract: TiO2nano-particle (TiO2NP) is widely used in industrial, household necessities, as well as medicinal products. However, the effect of TiO2NP on liver metabolic function has not been reported. In this study, after mice were orally administered TiO2NP (21nm) for 14days, the serum and liver tissues were assayed by biochemical analysis, real time quantitative polymerase chain reaction, western blot and transmission electron microscopy. The serum bilirubin was increased in a dose dependent manner. Deposition of TiO2NP in hepatocytes and the abnormality of microstructures was observed. Expression of metabolic genes involved in the endogenous and exogenous metabolism was modified, supporting the toxic phenotype. Collectively, oral administration of TiO2NP (21nm) led to deposition of particles in hepatocytes, mitochondrial edema, and the disturbance of liver metabolism function. These data suggested oral administration disrupts liver metabolic functions, which was more sensitive than regular approaches to detect material hepatotoxicity. This study provided useful information for risk analysis and regulation of TiO2NPs by administration agencies.
authors.affiliation: Ningbo College of Health Sciences, Ningbo 315100, China.
authors.forename: Julin
authors.initials: J
authors.lastname: Yang
authors.affiliation: Medical School of Ningbo University, Ningbo 315211, China.
authors.forename: Min
authors.initials: M
authors.lastname: Luo
authors.affiliation: Medical School of Ningbo University, Ningbo 315211, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Tan
authors.affiliation: Medical School of Ningbo University, Ningbo 315211, China.
authors.forename: Manyun
authors.initials: M
authors.lastname: Dai
authors.affiliation: Medical School of Ningbo University, Ningbo 315211, China.
authors.forename: Minzhu
authors.initials: M
authors.lastname: Xie
authors.affiliation: Medical School of Ningbo University, Ningbo 315211, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Lin
authors.affiliation: Medical School of Ningbo University, Ningbo 315211, China.
authors.forename: Huiying
authors.initials: H
authors.lastname: Hua
authors.affiliation: Medical School of Ningbo University, Ningbo 315211, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Medical School of Ningbo University, Ningbo 315211, China.
authors.forename: Jinshun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Medical School of Ningbo University, Ningbo 315211, China. Electronic address: liuaiming@nbu.edu.cn.
authors.forename: Aiming
authors.initials: A
authors.lastname: Liu
mesh_terms: D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D001219:Aspartate Aminotransferases / Q000097:blood; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D053768:Metal Nanoparticles / Q000633:toxicity*; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D012333:RNA, Messenger / Q000378:metabolism; D014025:Titanium / Q000633:toxicity*
chemical_list: D051017:Apoptosis Regulatory Proteins; D016207:Cytokines; D012333:RNA, Messenger; C009495:titanium dioxide; D003577:Cytochrome P-450 Enzyme System; D014025:Titanium; D014453:Glucuronosyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Cholestasis; Jaundice; Liver metabolism; Nano-titanium dioxide