title: Liver-specific microRNAs as biomarkers of nanomaterial-induced liver damage.
abstract: Although nanomaterials are being used in various fields, their safety is not yet sufficiently understood. We have been attempting to establish a nanomaterials safety-assessment system by using biomarkers to predict nanomaterial-induced adverse biological effects. Here, we focused on microRNAs (miRNAs) because of their tissue-specific expression and high degree of stability in the blood. We previously showed that high intravenous doses of silica nanoparticles of 70 nm diameter (nSP70) induced liver damage in mice. In this study, we compared the effectiveness of serum levels of liver-specific or -enriched miRNAs (miR-122, miR-192, and miR-194) with that of conventional hepatic biomarkers (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) as biomarkers for nSP70. After mice had been treated with nSP70, their serum miRNAs levels were measured by using quantitative RT-PCR. Serum levels of miR-122 in nSP70-treated mice were the highest among the three miRNAs. The sensitivity of miR-122 for liver damage was at least as good as those of ALT and AST. Like ALT and AST, miR-122 may be a useful biomarker of nSP70. We believe that these findings will help in the establishment of a nanomaterials safety-assessment system.
authors.affiliation: Laboratory of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nagano
authors.forename: Kazuma
authors.initials: K
authors.lastname: Higashisaka
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kunieda
authors.forename: Yuki
authors.initials: Y
authors.lastname: Iwahara
authors.forename: Kota
authors.initials: K
authors.lastname: Tanaka
authors.forename: Kazuya
authors.initials: K
authors.lastname: Nagano
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Abe
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Kamada
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Tsunoda
authors.forename: Hiromi
authors.initials: H
authors.lastname: Nabeshi
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Yoshioka
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Tsutsumi
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood*; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood*; D005260:Female; D008099:Liver / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000097:blood*; D053758:Nanoparticles / Q000633:toxicity*; D010316:Particle Size; D012680:Sensitivity and Specificity; D012822:Silicon Dioxide / Q000633:toxicity
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D012822:Silicon Dioxide