Comprehensive assessment of nephrotoxicity of intravenously administered sodium-oleate-coated ultra-small superparamagnetic iron oxide (USPIO) and titanium dioxide (TiO2) nanoparticles in rats

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.