Distribution and toxicity evaluation of ZnO dispersion nanoparticles in single intravenously exposed mice

  • Fujihara Junko
    Department of Legal Medicine, Shimane University Faculty of Medicine
  • Tongu Miki
    Shin-yamanote Hospital, Higashi-murayama
  • Hashimoto Hideki
    Center for the Promotion of Project Research, Shimane University
  • Yamada Takaya
    Department of Experimental Animals, Center for Integrated Research in Science, Shimane University Faculty of Medicine
  • Kimura-Kataoka Kaori
    Department of Legal Medicine, Shimane University Faculty of Medicine
  • Yasuda Toshihiro
    Division of Medical Genetics and Biochemistry, Faculty of Medical Sciences, University of Fukui
  • Fujita Yasuhisa
    Interdisciplinary Graduate School of Science and Engineering, Shimane University
  • Takeshita Haruo
    Department of Legal Medicine, Shimane University Faculty of Medicine

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Abstract

ZnO nanoparticles (NPs) have been widely used in various commercial products. Application of ZnO NPs is expected to apply to cancer diagnosis and therapy, used as drug delivery carriers. In the present study, the lethal dose 50 (LD50) of intravenously administered ZnO NPs (0.3 mg/kg) was calculated in mice. Blood kinetics and tissue distribution of a toxic dose of ZnO NPs (0.2 mg/kg, 0.05 mg/kg) were investigated after intravenous exposure. In addition, 8-hydroxy-2'-deoxyguanosine (8-OHdG) was evaluated. Following the injection, ZnO NPs were rapidly removed from the blood and distributed to organs. Pulmonary emphysema was observed pathologically study in mice at 3 days after the 0.2 mg/kg dose and at 6 days after the 0.05 mg/kg dose. ZnO NPs were mainly accumulated in the lung and spleen within 60 min. From the long-term tissue distribution study, the liver showed peak concentration at 6 days, and spleen peaked at 1 day. The lungs kept high levels until 6 days. Tissue distribution and pathological study showed that the spleen, liver, and lungs are target organs for ZnO NPs. Accumulation in the liver and spleen may be due to the phagocytosis by macrophages. A dose-dependent increase in 8-OHdG was observed in mice treated with ZnO NPs. This study is the first to show information on kinetics and target organs following intravenous ZnO injection. J. Med. Invest. 62: 45-50, February, 2015

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