title: Organ biodistribution, clearance, and genotoxicity of orally administered zinc oxide nanoparticles in mice.
abstract: Abstract   Understanding tissue biodistribution and clearance of zinc oxide nanoparticles (ZnO-NPs) is necessary for its risk assessment. Both fed and intraperitoneally injected ZnO-NPs (2.5 g/kg) were absorbed into circulation (within 30 min post-dosing), then biodistributed to the liver, spleen, and kidney. Intraperitoneally injected ZnO-NPs remained in serum for 72 h and could more effectively spread to the heart, lung, and testes, whereas the clearance for fed ZnO-NPs in serum began 6 h after oral administration. Compared with zinc oxide microparticles (ZnO-MPs), ZnO-NPs exhibited much higher absorptivity and tissue biodistribution in fed treatment. A greater fraction of fed ZnO-NPs localised in the liver resulted in transient histopathological lesions. However, superoxide generation and cytotoxicity were showed in vitro treatment with ZnO-NPs (above 20 μg/mL). Considering both in vitro and in vivo data, the ZnO-NPs induced acute liver toxicity which was in compliance with its absorption, biodistribution, and clearance.
authors.affiliation: Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Ching-Hao
authors.initials: CH
authors.lastname: Li
authors.forename: Chuan-Chou
authors.initials: CC
authors.lastname: Shen
authors.forename: Yu-Wen
authors.initials: YW
authors.lastname: Cheng
authors.forename: Shih-Hsuan
authors.initials: SH
authors.lastname: Huang
authors.forename: Chung-Che
authors.initials: CC
authors.lastname: Wu
authors.forename: Chen-Chieh
authors.initials: CC
authors.lastname: Kao
authors.forename: Jiunn-Wang
authors.initials: JW
authors.lastname: Liao
authors.forename: Jaw-Jou
authors.initials: JJ
authors.lastname: Kang
mesh_terms: D000042:Absorption; D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015162:Micronucleus Tests; D053758:Nanoparticles / Q000008:administration & dosage / Q000633:toxicity*; D010316:Particle Size; D012995:Solubility; D013154:Spleen / Q000737:chemistry / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014018:Tissue Distribution; D023382:Toxicity Tests, Acute; D015034:Zinc Oxide / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*
chemical_list: D013481:Superoxides; D015034:Zinc Oxide