title: The Effects of Extensive Glomerular Filtration of Thin Graphene Oxide Sheets on Kidney Physiology.
abstract: Understanding how two-dimensional (2D) nanomaterials interact with the biological milieu is fundamental for their development toward biomedical applications. When thin, individualized graphene oxide (GO) sheets were administered intravenously in mice, extensive urinary excretion was observed, indicating rapid transit across the glomerular filtration barrier (GFB). A detailed analysis of kidney function, histopathology, and ultrastructure was performed, along with the in vitro responses of two highly specialized GFB cells (glomerular endothelial cells and podocytes) following exposure to GO. We investigated whether these cells preserved their unique barrier function at doses 100 times greater than the dose expected to reach the GFB in vivo. Both serum and urine analyses revealed that there was no impairment of kidney function up to 1 month after injection of GO at escalating doses. Histological examination suggested no damage to the glomerular and tubular regions of the kidneys. Ultrastructural analysis by transmission electron microscopy showed absence of damage, with no change in the size of podocyte slits, endothelial cell fenestra, or the glomerular basement membrane width. The endothelial and podocyte cell cultures regained their full barrier function after >48 h of GO exposure, and cellular uptake was significant in both cell types after 24 h. This study provided a previously unreported understanding of the interaction between thin GO sheets with different components of the GFB in vitro and in vivo to highlight that the glomerular excretion of significant amounts of GO did not induce any signs of acute nephrotoxicity or glomerular barrier dysfunction.
authors.forename: Dhifaf A
authors.initials: DA
authors.lastname: Jasim
authors.forename: Stephanie
authors.initials: S
authors.lastname: Murphy
authors.forename: Leon
authors.initials: L
authors.lastname: Newman
authors.forename: Aleksandr
authors.initials: A
authors.lastname: Mironov
authors.forename: Eric
authors.identifier: 0000-0003-1340-0970
authors.initials: E
authors.lastname: Prestat
authors.affiliation: Department of Pediatric Nephrology, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust (CMFT), Manchester Academic Health Science Centre , Manchester M13 9NT, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: McCaffrey
authors.affiliation: University of Strasbourg, CNRS, Immunopathology and Therapeutic Chemistry, UPR 3572, 67000 Strasbourg, France.
authors.forename: Cécilia
authors.initials: C
authors.lastname: Ménard-Moyon
authors.forename: Artur Filipe
authors.initials: AF
authors.lastname: Rodrigues
authors.affiliation: University of Strasbourg, CNRS, Immunopathology and Therapeutic Chemistry, UPR 3572, 67000 Strasbourg, France.
authors.forename: Alberto
authors.initials: A
authors.lastname: Bianco
authors.forename: Sarah
authors.identifier: 0000-0001-5509-6706
authors.initials: S
authors.lastname: Haigh
authors.affiliation: Department of Pediatric Nephrology, Royal Manchester Children's Hospital, Central Manchester University Hospitals NHS Foundation Trust (CMFT), Manchester Academic Health Science Centre , Manchester M13 9NT, United Kingdom.
authors.forename: Rachel
authors.initials: R
authors.lastname: Lennon
authors.forename: Kostas
authors.initials: K
authors.lastname: Kostarelos
mesh_terms: D000818:Animals; D042783:Endothelial Cells; D050533:Glomerular Basement Membrane / Q000502:physiology*; D006108:Graphite; D051379:Mice; D049329:Nanostructures; D010087:Oxides; D050199:Podocytes
chemical_list: D010087:Oxides; D006108:Graphite
keywords: 2D crystals; carbon nanomaterial; nanotoxicology; urinary excretion