Health effects of selected nanoparticles in vivo: liver function and hepatotoxicity following intravenous injection of titanium dioxide and Na-oleate-coated iron oxide nanoparticles in rodents

Abstract

The study determined the effect of intravenous administration of acutely toxic or sub-lethal doses of Na-oleate-coated Fe₃O₄ (OC-Fe₃O₄) nanoparticles (NPs) on liver structure and function in Wistar rats, compared to titanium dioxide (TiO₂) NPs and saline-injected controls. The acute study, using a modified OECD 425 progressive dosing procedure, found LD₅₀ values of 59.22 and 36.42 mg/kg for TiO₂ and OC-Fe₃O₄ NPs, respectively. In the sub-lethal study, rats were either injected with saline (negative controls), a sub-lethal reference (0.592 mg/kgTiO₂ NPs, equal to 1% of LD₅₀ on a body weight basis) or OC-Fe₃O₄ NPs in doses equivalent to 0.1, 1 or 10% of the LD₅₀, respectively (corresponding to 0.0364, 0.364 and 3.64 mg Fe₃O₄/kg body weight). Animals were sampled 24 h, 1, 2 and 4 weeks post-injection for adverse effects. Mitochondrial respiration was significantly increased 2 weeks after injection of 10% OC-Fe₃O₄ NPs compared to controls, but the effect was transient. Cholesterol and triacylglycerol concentrations in the liver tissue did not increase in any treatment. There were some disturbances to antioxidant enzymes after OC-Fe₃O₄ NPs treatment in the livers of animals 1 week post-exposure; with the most sensitive changes occurring in glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities. Lipidosis and mild necrosis with changes in sinusoid space were also observed in histological sections of the liver. Overall, these data suggest that the liver likely retains functional integrity with acute and sub-lethal doses of OC-Fe₃O₄ NPs, albeit with some stimulation of redox defences and evidence of some tissue injury.

• in vivo nanotoxicology
• Na-oleate-coated Fe₃O₄
• TiO₂ nanoparticles
• liver toxicity

Acknowledgements

Analyses of size distribution and pH of both types of NPs were done in University of Venice (by equipment NICOMP 370, submicron particle sizer, Nicomp International, Inc., New York, NY, USA). Michael Hockings and Lewis Young are thanked for their help in preparing the liver sections at Plymouth University. The authors acknowledge the support of the European Commission 7th Framework Programme for the NanoTEST project (Health-2007-1.3-4, Contract no: 201335). The work was also supported by EC FP7 QualityNano [INFRA-2010-1.131], Contract no: 214547-2, and EC FP7 NANoREG, [NMP.2012.1.3-3], Contract no: 310584.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.