title: Comprehensive assessment of nephrotoxicity of intravenously administered sodium-oleate-coated ultra-small superparamagnetic iron oxide (USPIO) and titanium dioxide (TiO2) nanoparticles in rats.
abstract: As a main excretory organ, kidney is predisposed to direct/indirect injury. We addressed the potential nephrotoxic effects following expositions of healthy rats to nanoparticle (NP) loads relevant to humans in a situation of 100% bioavailability. Up to 4 weeks after administration, a single iv bolus of oleate-coated ultra-small superparamagnetic iron oxide NPs (in dose of 0.1%, 1.0% and 10.0% of LD50) or TiO2 NPs (1.0% of LD50) did not elicit decline in renal function, damage to proximal tubules, alterations in: renal histology or expression of pro-inflammatory/pro-fibrotic genes, markers of systemic or local renal micro-inflammation or oxidative damage. Antioxidant enzyme activities in renal cortex, mildly elevated at 24 h, completely restored at later time points. Data obtained by multifaceted approach enable the prediction of human nephrotoxicity during preclinical studies, and may serve as comparison for alternative testing strategies using in vitro and in silico methods essential for the NP-nephrotoxicity risk assessment.
authors.affiliation: Institute of Molecular Biomedicine, Medical Faculty, Comenius University , Bratislava , Slovakia.
authors.forename: Katarína
authors.initials: K
authors.lastname: Šebeková
authors.forename: Mária
authors.initials: M
authors.lastname: Dušinská
authors.forename: Kristína
authors.initials: K
authors.lastname: Simon Klenovics
authors.forename: Radana
authors.initials: R
authors.lastname: Kollárová
authors.forename: Peter
authors.initials: P
authors.lastname: Boor
authors.forename: Anton
authors.initials: A
authors.lastname: Kebis
authors.forename: Marta
authors.initials: M
authors.lastname: Staruchová
authors.forename: Barbora
authors.initials: B
authors.lastname: Vlková
authors.forename: Peter
authors.initials: P
authors.lastname: Celec
authors.forename: Július
authors.initials: J
authors.lastname: Hodosy
authors.forename: Ladislav
authors.initials: L
authors.lastname: Bačiak
authors.forename: Radka
authors.initials: R
authors.lastname: Tušková
authors.forename: Milan
authors.initials: M
authors.lastname: Beňo
authors.forename: Jana
authors.initials: J
authors.lastname: Tulinská
authors.forename: Jana
authors.initials: J
authors.lastname: Príbojová
authors.forename: Dagmar
authors.initials: D
authors.lastname: Bilaničová
authors.forename: Giulio
authors.initials: G
authors.lastname: Pojana
authors.forename: Antonio
authors.initials: A
authors.lastname: Marcomini
authors.forename: Katarína
authors.initials: K
authors.lastname: Volkovová
mesh_terms: D000818:Animals; D005260:Female; D005355:Fibrosis / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced; D007668:Kidney / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced; D007928:Lethal Dose 50; D009682:Magnetic Resonance Spectroscopy; D058185:Magnetite Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D019301:Oleic Acid / Q000737:chemistry*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014025:Titanium / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D058185:Magnetite Nanoparticles; D014409:Tumor Necrosis Factor-alpha; C009495:titanium dioxide; D019301:Oleic Acid; C013173:osteum; D014025:Titanium