title: Investigation of in vitro cytotoxicity of the redox state of ionic iron in neuroblastoma cells.
abstract: BACKGROUND
  there is an intimate relation between transition metals and cell homeostasis due to the physiological necessity of metals in vivo. Particularly, iron (ferrous and ferric state) is utilized in many physiological processes of the cell but in excess has been linked with negative role contributing in many neurodegenerative processes.
  
  
  OBJECTIVE
  the aim of this study was to investigate which oxidation state of ionic iron (Ferrous (II) versus Ferric (III)) is more toxic to neuronal cells (SHSY(5)Y).
  
  
  METHODS
  The neuroblastoma (SHSY(5)Y) cells were exposed to varying concentration of ferric and ferrous iron. Morphological studies using immunofluorescence staining and microscopic analysis as confirmed by intracellular glutathione (GSH) test demonstrated oxidative stress to cells in iron microenvironment. In addition, MTT assay was performed to evaluate the viability and metabolic state of the cells.
  
  
  RESULTS
  the results showed that ferrous form has significantly higher toxicity compared to the ferric ionic state of higher concentration. In addition, microscopic analysis shows cell fenestration at higher concentrations and swelling at intermediate ferric dosages as demonstrated by atomic force microscopy (AFM). Interestingly, the addition of a differentiation inducing factor, trans-retinoic rcid (RA) retains significant viability and morphological features of the cells irrespective of the ionic state of the iron. AFM images revealed clustered aggregates arising from iron chelation with RA.
  
  
  CONCLUSIONS
  the results indicate that Fe (II) has more toxic effects on cells. In addition, it could be an interesting finding with respect to the antioxidant properties of RA as a chelating agent for the neurodegenerative therapeutics.
authors.affiliation: European School of Molecular Medicine (SEMM), IFOM-IEO Campus, via Adamello, 16, I-20139 Milan, Italy ; Interdisciplinary Centre for Nanostructure Materials and Interfaces (CIMAINA), Department of Physics, via Celoria 16, University of Milan, Milan, Italy.
authors.forename: Ajay Vikram
authors.initials: AV
authors.lastname: Singh
authors.forename: Varun
authors.initials: V
authors.lastname: Vyas
authors.forename: Erica
authors.initials: E
authors.lastname: Montani
authors.forename: Erica
authors.initials: E
authors.lastname: Maontani
authors.forename: Daniele
authors.initials: D
authors.lastname: Cartelli
authors.forename: Dario
authors.initials: D
authors.lastname: Parazzoli
authors.forename: Amanda
authors.initials: A
authors.lastname: Oldani
authors.forename: Giulia
authors.initials: G
authors.lastname: Zeri
authors.forename: Elisa
authors.initials: E
authors.lastname: Orioli
authors.forename: Donato
authors.initials: D
authors.lastname: Gemmati
authors.forename: Paolo
authors.initials: P
authors.lastname: Zamboni