title: Silica nanoparticles as hepatotoxicants.
abstract: Nano-size materials are increasingly used in cosmetics, diagnosis, imaging and drug delivery, but the toxicity of the nano-size materials has never been fully investigated. Here, we investigated the relationship between particle size and toxicity using silica particles with diameters of 70, 300 and 1000 nm (SP70, SP300, and SP1000) as a model material. To evaluate acute toxicity, we first performed histological analysis of liver, spleen, kidney and lung by intravenous administration of silica particles. SP70-induced liver injury at 30 mg/kg body weight, while SP300 or 1000 had no effect even at 100 mg/kg. Administration of SP70 dose-dependently increased serum markers of liver injury, serum aminotransferase and inflammatory cytokines. Repeated administration of SP70 twice a week for 4 weeks, even at 10mg/kg, caused hepatic fibrosis. Taken together, nano-size materials may be hepatotoxic, and these findings will be useful for future development in nanotechnology-based drug delivery system.
authors.affiliation: Laboratory of Bio-Functional Molecular Chemistry, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Nishimori
authors.forename: Masuo
authors.initials: M
authors.lastname: Kondoh
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Isoda
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Tsunoda
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Tsutsumi
authors.forename: Kiyohito
authors.initials: K
authors.lastname: Yagi
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage / Q000633:toxicity*; D010316:Particle Size; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D012822:Silicon Dioxide