title: 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.
authors.affiliation: Slovak Medical University , Bratislava , Slovakia .
authors.forename: Katarina
authors.initials: K
authors.lastname: Volkovova
authors.forename: Richard D
authors.initials: RD
authors.lastname: Handy
authors.forename: Marta
authors.initials: M
authors.lastname: Staruchova
authors.forename: Jana
authors.initials: J
authors.lastname: Tulinska
authors.forename: Anton
authors.initials: A
authors.lastname: Kebis
authors.forename: Jana
authors.initials: J
authors.lastname: Pribojova
authors.forename: Olga
authors.initials: O
authors.lastname: Ulicna
authors.forename: Jarmila
authors.initials: J
authors.lastname: Kucharská
authors.forename: Maria
authors.initials: M
authors.lastname: Dusinska
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D005290:Ferric Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000187:drug effects / Q000378:metabolism; D007275:Injections, Intravenous; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity*; D009336:Necrosis / Q000139:chemically induced / Q000473:pathology; D019301:Oleic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D018384:Oxidative Stress; D051381:Rats; D014025:Titanium / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity*
chemical_list: D000975:Antioxidants; D005290:Ferric Compounds; C009495:titanium dioxide; C000499:ferric oxide; D019301:Oleic Acid; D014025:Titanium; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase
keywords: Na-oleate-coated Fe3O4; TiO2 nanoparticles; in vivo nanotoxicology; liver toxicity