title: Disturbance of ion environment and immune regulation following biodistribution of magnetic iron oxide nanoparticles injected intravenously.
abstract: Although it is expected that accumulation of metal oxide nanoparticles that can induce redox reaction in the biological system may influence ion homeostasis and immune regulation through generation of free radicals, the relationship is still unclear. In this study, mice received magnetic iron oxide nanoparticles (M-FeNPs, 2 and 4 mg/kg) a single via the tail vein, and their distribution in tissues was investigated over time (1, 4, and 13 weeks). In addition, we evaluated the effects on homeostasis of redox reaction-related elements, the ion environment and immune regulation. The iron level in tissues reached at the maximum on 4 weeks after injection and M-FeNPs the most distributed in the spleen at 13 weeks. Additionally, levels of redox reaction-related elements in tissues were notably altered since 1 week post-injection. While levels of K(+) and Na(+) in tissue tended to decrease with time, Ca(2+) levels reached to the maximum at 4 weeks post-injection. On 13 weeks post-injection, the increased percentages of neutrophils and eosinophils, the enhanced release of LDH, and the elevated secretion of IL-8 and IL-6 were clearly observed in the blood of M-FeNP-treated mice compared to the control. While expression of antigen presentation related-proteins and the maturation of dendritic cells were markedly inhibited following distribution of M-FeNPs, the expression of several chemokines, including CXCR2, CCR5, and CD123, was enhanced on the splenocytes of the treated groups. Taken together, we suggest that accumulation of M-FeNPs may induce adverse health effects by disturbing homeostasis of the immune regulation and ion environment.
authors.affiliation: Myunggok Eye Research Institute, Konyang University, Daejeon 302-718, South Korea. Electronic address: pejtoxic@hanmail.net.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Park
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon 443-749, South Korea.
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Seoul Center, Korea Basic Science Institute, Seoul 126-16, South Korea.
authors.forename: Cheolho
authors.initials: C
authors.lastname: Yoon
authors.affiliation: Department of Chemical Engineering, Kwangwoon University, Seoul 139-701, South Korea.
authors.forename: Younghun
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Department of Community Health and Epidemiology, Faculty of Medicine, Dalhousie University, Halifax, Canada.
authors.forename: Jong Sung
authors.initials: JS
authors.lastname: Kim
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006706:Homeostasis; D007155:Immunologic Factors / Q000378:metabolism*; D007275:Injections, Intravenous; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D058185:Magnetite Nanoparticles / Q000009:adverse effects* / Q000737:chemistry; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D005290:Ferric Compounds; D007155:Immunologic Factors; D015850:Interleukin-6; D016209:Interleukin-8; D058185:Magnetite Nanoparticles; C000499:ferric oxide; D012964:Sodium; D011188:Potassium
keywords: Distribution; Immunotoxicity; Ion environment; Iron oxide nanoparticles; Magnetite