title: Iron overload by Superparamagnetic Iron Oxide Nanoparticles is a High Risk Factor in Cirrhosis by a Systems Toxicology Assessment.
abstract: Superparamagnetic iron oxide nanoparticles (SPIONs) as a contrast agent have been widely used in magnetic resonance imaging for tumor diagnosis and theranostics. However, there has been safety concern of SPIONs with cirrhosis related to excess iron-induced oxidative stress. In this study, the impact of iron overload by SPIONs was assessed on a mouse cirrhosis model. A single dose of SPION injection at 0.5 or 5 mg Fe/kg in the cirrhosis group induced a septic shock response at 24 h with elevated serum levels of liver and kidney function markers and extended impacts over 14 days including high levels of serum cholesterols and persistent low serum iron level. In contrast, full restoration of liver functions was found in the normal group with the same dosages over time. Analysis with PCR array of the toxicity pathways revealed the high dose of SPIONs induced significant expression changes of a distinct subset of genes in the cirrhosis liver. All these results suggested that excess iron of the high dose of SPIONs might be a risk factor for cirrhosis because of the marked impacts of elevated lipid metabolism, disruption of iron homeostasis and possibly, aggravated loss of liver functions.
authors.affiliation: Department of Nanomedicine &Biopharmaceuticals, National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Yushuang
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Nanomedicine &Biopharmaceuticals, National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Mengzhu
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Nanomedicine &Biopharmaceuticals, National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Nanomedicine &Biopharmaceuticals, National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Division of Viral Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, United States of America.
authors.forename: Hang
authors.initials: H
authors.lastname: Xie
authors.affiliation: Department of Nanomedicine &Biopharmaceuticals, National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Qibing
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000009:adverse effects / Q000627:therapeutic use; D004195:Disease Models, Animal; D006801:Humans; D019190:Iron Overload / Q000139:chemically induced / Q000503:physiopathology; D008099:Liver / Q000187:drug effects* / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000009:adverse effects* / Q000627:therapeutic use; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D000068936:Theranostic Nanomedicine; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D003287:Contrast Media; D058185:Magnetite Nanoparticles