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.

NanoTEST in a Nutshell

“…OC-Fe 3 O 4 NP deposits were clearly seen in whole liver parenchyma in contrast to Magnetic Resonance Imaging (MRI) of the kidney, confirming that liver is the main target organ of these NPs. Highest TiO 2 NPs levels were revealed also in liver, followed by spleen, and lung (Sebekova et al, 2014). The data reported by Volkovova et al (2015) suggest that the liver likely retains functional integrity with sub-lethal doses of OC-Fe 3 O 4 NPs, albeit with some stimulation of redox defences and evidence of some tissue injury shortly after the injection.…”

“…The data reported by Volkovova et al (2015) suggest that the liver likely retains functional integrity with sub-lethal doses of OC-Fe 3 O 4 NPs, albeit with some stimulation of redox defences and evidence of some tissue injury shortly after the injection. Data on nephrotoxicity were published previously (Sebekova et al, 2014) showing mild or no effect and the majority of results addressing other organ and tissue toxicity are under preparation.…”

Applications of Nanoparticles in the Detection and Treatment of Kidney Diseases

“…Sodium-oleate-coated USPIO have been studied in vivo in a rat model administered as a single dose at varying concentrations and followed for 1 month. There was no change in renal function or cellular morphology 116 . While these studies highlight some of the properties of NPs and how they may affect the kidney, there exist no in vivo human studies that particularly investigate the toxicology profiles of these biological NPs.…”

Relationship between lymphocyte DNA fragmentation and dose of iron oxide (Fe₂O₃) and silicon oxide (SiO₂) nanoparticles

“…The current knowledge regarding the effect of NP size on biological systems is still incomplete. However, NP properties associated with particle size are crucial factors that determine the biological safety of NPs, and can directly affect feasibility of NP in biomedical applications (Alarifi et al, 2014;Šebeková et al, 2014). The study of nanotoxicology has shown that NPs with the same composition but different magnetic surface charge can produce toxic damage (Kut et al, 2012;Ma et al, 2012).…”