title: Nano zerovalent iron particles induce pulmonary and cardiovascular toxicity in an in vitro human co-culture model.
abstract: Despite promising environmental applications for nano zerovalent iron (nZVI), concerns remain about the potential accumulation and toxic effects of nZVI particles. Here, we use an alveolar-capillary co-culture model to investigate a possible link between low-level epithelial exposure to nZVI and pulmonary and cardiovascular toxicity. While nZVI was unable to pass through the epithelial barrier into the endothelium, nZVI exposure did cause oxidative and inflammatory responses in both epithelial and endothelial cells. Therefore, toxic effects induced by nZVI are not restricted to epithelial cells but can be transferred into the endothelium. Communication between A549 and EA.hy926 cells is responsible for amplification of nZVI-induced toxic responses. Decreases in transepithelial electrical resistance and zonula occludens proteins after epithelial exposure to nZVI impaired epithelial barrier integrity. Increases in oxidized α1-antitrypsin and oxidized low-density lipoprotein in the co-culture model suggest that nZVI exposure increases the risk of chronic obstructive pulmonary disease and atherosclerosis. Therefore, inhalation of nZVI has the potential to induce cardiovascular disease through oxidative and inflammatory mediators produced from the damaged lung epithelium in chronic lung diseases.
authors.affiliation: a Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences , Suzhou , China .|b School of Life Sciences, Shanghai University , Shanghai , China .
authors.forename: Zhelin
authors.initials: Z
authors.lastname: Sun
authors.affiliation: a Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences , Suzhou , China .
authors.forename: Lingyan
authors.initials: L
authors.lastname: Yang
authors.affiliation: c Department of Civil Engineering , National Chi Nan University , Nantou , Taiwan .
authors.forename: Ku-Fan
authors.initials: KF
authors.lastname: Chen
authors.affiliation: d Department of Food and Beverage Management , Taipei College of Maritime Technology , Taipei , Taiwan .
authors.forename: Guan-Wen
authors.initials: GW
authors.lastname: Chen
authors.affiliation: e Department of Environmental Science and Engineering , Tunghai University , Taichung , Taiwan .
authors.forename: Yen-Ping
authors.initials: YP
authors.lastname: Peng
authors.affiliation: f Institute of Biomedical Engineering & Nanomedicine, National Health Research Institutes , Miaoli , Taiwan .
authors.forename: Jen-Kun
authors.initials: JK
authors.lastname: Chen
authors.affiliation: a Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences , Suzhou , China .
authors.forename: Guangli
authors.initials: G
authors.lastname: Suo
authors.affiliation: a Key Laboratory of Nano-Bio Interface, Division of Nanobiomedicine, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences , Suzhou , China .
authors.forename: Jiantao
authors.initials: J
authors.lastname: Yu
authors.affiliation: g Research Center for Environmental Changes, Academia Sinica , Taipei , Taiwan , and.
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Wang
authors.affiliation: h Department of Biotechnology , National Formosa University , Yunlin , Taiwan.
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Lin
mesh_terms: D000072283:A549 Cells; D002319:Cardiovascular System / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007501:Iron / Q000737:chemistry / Q000633:toxicity*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008168:Lung / Q000187:drug effects*; D008954:Models, Biological; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D010084:Oxidation-Reduction; D013499:Surface Properties; D000515:alpha 1-Antitrypsin / Q000378:metabolism
chemical_list: D008077:Lipoproteins, LDL; D000515:alpha 1-Antitrypsin; C099252:oxidized low density lipoprotein; D007501:Iron
keywords: Atherosclerosis; COPD; epithelial barrier integrity; inflammation; oxidative stress