title: Comparison of manganese oxide nanoparticles and manganese sulfate with regard to oxidative stress, uptake and apoptosis in alveolar epithelial cells.
abstract: Due to their physicochemical characteristics, metal oxide nanoparticles (NPs) interact differently with cells compared to larger particles or soluble metals. Oxidative stress and cellular metal uptake were quantified in rat type II alveolar epithelial cells in culture exposed to three different NPs: manganese(II,III) oxide nanoparticles (Mn(3)O(4)-NPs), the soluble manganese sulfate (Mn-salt) at corresponding equivalent doses, titanium dioxide (TiO(2)-NPs) and cerium dioxide nanoparticles (CeO(2)-NPs). In the presence of reactive oxygen species an increased apoptosis rate was hypothesized. Oxidative stress was assessed by detection of fluorescently labeled reactive oxygen species and by measuring intracellular oxidized glutathione. Catalytic activity was determined by measuring catalyst-dependent oxidation of thiols (DTT-assay) in a cell free environment. Inductively coupled plasma mass spectrometry was used to quantify cellular metal uptake. Apoptosis rate was determined assessing the activity of caspase-3 and by fluorescence microscopic quantification of apoptotic nuclei. Reactive oxygen species were mainly generated in cells treated with Mn(3)O(4)-NPs. Only Mn(3)O(4)-NPs oxidized intracellular glutathione. Catalytic activity could be exclusively shown for Mn(3)O(4)-NPs. Cellular metal uptake was similar for all particles, whereas Mn-salt could hardly be detected within the cell. Apoptosis was induced by both, Mn(3)O(4)-NPs and Mn-salt. The combination of catalytic activity and capability of passing the cell membrane contributes to the toxicity of Mn(3)O(4)-NPs. Apoptosis of samples treated with Mn-salt is triggered by different, potentially extracellular mechanisms.
authors.affiliation: Institute of Anesthesiology, University Hospital Zurich, Switzerland.
authors.forename: Ramon
authors.initials: R
authors.lastname: Frick
authors.forename: Björn
authors.initials: B
authors.lastname: Müller-Edenborn
authors.forename: Andreas
authors.initials: A
authors.lastname: Schlicker
authors.forename: Barbara
authors.initials: B
authors.lastname: Rothen-Rutishauser
authors.forename: David O
authors.initials: DO
authors.lastname: Raemy
authors.forename: Detlef
authors.initials: D
authors.lastname: Günther
authors.forename: Bodo
authors.initials: B
authors.lastname: Hattendorf
authors.forename: Wendelin
authors.initials: W
authors.lastname: Stark
authors.forename: Beatrice
authors.initials: B
authors.lastname: Beck-Schimmer
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D005978:Glutathione / Q000378:metabolism; D020287:In Situ Nick-End Labeling; D017895:Manganese Compounds; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D010087:Oxides / Q000633:toxicity*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013054:Spectrophotometry, Atomic; D013431:Sulfates / Q000633:toxicity*
chemical_list: D017895:Manganese Compounds; D010087:Oxides; D017382:Reactive Oxygen Species; D013431:Sulfates; C027424:manganese oxide; D005978:Glutathione; C039798:manganese sulfate