Intratracheal instillation of cerium oxide nanoparticles induces hepatic toxicity in male Sprague-Dawley rats

Background Cerium oxide (CeO2) nanoparticles have been posited to have both beneficial and toxic effects on biological systems. Herein, we examine if a single intratracheal instillation of CeO2 nanoparticles is associated with systemic toxicity in male Sprague-Dawley rats. Methods and results Compared with control animals, CeO2 nanoparticle exposure was associated with increased liver ceria levels, elevations in serum alanine transaminase levels, reduced albumin levels, a diminished sodium-potassium ratio, and decreased serum triglyceride levels (P < 0.05). Consistent with these data, rats exposed to CeO2 nanoparticles also exhibited reductions in liver weight (P < 0.05) and dose-dependent hydropic degeneration, hepatocyte enlargement, sinusoidal dilatation, and accumulation of granular material. No histopathological alterations were observed in the kidney, spleen, and heart. Analysis of serum biomarkers suggested an elevation of acute phase reactants and markers of hepatocyte injury in the rats exposed to CeO2 nanoparticles. Conclusion Taken together, these data suggest that intratracheal instillation of CeO2 nanoparticles can result in liver damage.

[1]  L. Ren,et al.  In vitro and in vivo studies on gelatin-siloxane nanoparticles conjugated with SynB peptide to increase drug delivery to the brain , 2012, International Journal of Nanomedicine.

[2]  V. Castranova,et al.  Cerium oxide nanoparticle-induced pulmonary inflammation and alveolar macrophage functional change in rats , 2011, Nanotoxicology.

[3]  Qingxiu Wang,et al.  Systems toxicology used in nanotoxicology: mechanistic insights into the hepatotoxicity of nano-copper particles from toxicogenomics. , 2011, Journal of nanoscience and nanotechnology.

[4]  Flemming R Cassee,et al.  Exposure, Health and Ecological Effects Review of Engineered Nanoscale Cerium and Cerium Oxide Associated with its Use as a Fuel Additive , 2011, Critical reviews in toxicology.

[5]  F. Rossi,et al.  Cyclotron Production of Radioactive ${\hbox{CeO}} _{2}$ Nanoparticles and Their Application for In Vitro Uptake Studies , 2011, IEEE Transactions on NanoBioscience.

[6]  Qing Huang,et al.  Systematic influence induced by 3 nm titanium dioxide following intratracheal instillation of mice. , 2010, Journal of nanoscience and nanotechnology.

[7]  M. Yousef,et al.  Propolis prevents aluminium-induced genetic and hepatic damages in rat liver. , 2010, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[8]  Wei Bai,et al.  Lung deposition and extrapulmonary translocation of nano-ceria after intratracheal instillation , 2010, Nanotechnology.

[9]  Y. Liu,et al.  Potential health impact on mice after nasal instillation of nano-sized copper particles and their translocation in mice. , 2009, Journal of nanoscience and nanotechnology.

[10]  Sudipta Seal,et al.  Protection from radiation-induced pneumonitis using cerium oxide nanoparticles. , 2009, Nanomedicine : nanotechnology, biology, and medicine.

[11]  Jinhee Choi,et al.  Oxidative stress of CeO2 nanoparticles via p38-Nrf-2 signaling pathway in human bronchial epithelial cell, Beas-2B. , 2009, Toxicology letters.

[12]  A. Mathew,et al.  Cerium oxide nanoparticles prepared in self-assembled systems. , 2009, Advances in colloid and interface science.

[13]  A. Sezer,et al.  Curcumin attenuates the organ dysfunction caused by endotoxemia in the rat. , 2008, Nutrition.

[14]  Peter Jenkinson,et al.  Initial in vitro screening approach to investigate the potential health and environmental hazards of Envirox™ – a nanoparticulate cerium oxide diesel fuel additive , 2007, Particle and Fibre Toxicology.

[15]  M. Das,et al.  Auto-catalytic ceria nanoparticles offer neuroprotection to adult rat spinal cord neurons. , 2007, Biomaterials.

[16]  S. Seal,et al.  Superoxide dismutase mimetic properties exhibited by vacancy engineered ceria nanoparticles. , 2007, Chemical communications.

[17]  L. Rogers,et al.  Cardioprotective effects of cerium oxide nanoparticles in a transgenic murine model of cardiomyopathy. , 2007, Cardiovascular research.

[18]  H. Demirin,et al.  The effects of subchronic methidathion toxicity on rat liver: Role of antioxidant vitamins C and E , 2006, Cell Biology and Toxicology.

[19]  P. Costelli,et al.  Ca(2+)-dependent proteolysis in muscle wasting. , 2005, The international journal of biochemistry & cell biology.

[20]  V. Menon,et al.  Comparative effects of curcumin and an analogue of curcumin in carbon tetrachloride-induced hepatotoxicity in rats. , 2005, Basic & clinical pharmacology & toxicology.

[21]  G. Lu,et al.  Asymptomatic process of hepatic artery thrombosis in a patient after orthotopic liver transplantation. , 2004, Hepatobiliary & pancreatic diseases international : HBPD INT.

[22]  Y. Hsu,et al.  The hepatoprotective effects of Limonium sinense against carbon tetrachloride and β‐D‐galactosamine intoxication in rats , 2003, Phytotherapy research : PTR.

[23]  William M. Lee,et al.  Thrombopoietin in acute liver failure , 2003, Hepatology.

[24]  Nikolaou.  Emissions reduction of high and low polluting new technology vehicles equipped with a CeO2 catalytic system , 1999, The Science of the total environment.

[25]  I. Kushner,et al.  Acute-phase proteins and other systemic responses to inflammation. , 1999, The New England journal of medicine.

[26]  安田 準,et al.  Lactate dehydrogenase isoenzyme patterns in bovine liver tissue. , 1989, Nihon juigaku zasshi. The Japanese journal of veterinary science.

[27]  V. Feron,et al.  Effects of the exposure profile on the inhalation toxicity of carbon tetrachloride in male rats , 1987, Journal of applied toxicology : JAT.

[28]  Eggleston Jc,et al.  Oat cell carcinoma of the bronchus and the carcinoid syndrome. , 1975 .

[29]  Y. Yoshioka,et al.  Acute phase proteins as biomarkers for predicting the exposure and toxicity of nanomaterials. , 2011, Biomaterials.

[30]  M. Arslan,et al.  The age- and gender-dependent effects of desflurane and sevoflurane on rat liver. , 2010, Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie.

[31]  O. Sagol,et al.  The protective effects of carnosine and melatonin in ischemia-reperfusion injury in the rat liver. , 2009, Acta histochemica.

[32]  Cuihong Jin,et al.  [Comparative study of the effect on oxidative damage in rats inhaled by nano-sized and micro-sized silicon dioxide]. , 2008, Wei sheng yan jiu = Journal of hygiene research.

[33]  Zissis Samaras,et al.  Hazard and risk assessment of a nanoparticulate cerium oxide-based diesel fuel additive - a case study. , 2008, Inhalation toxicology.

[34]  J. C. Eggleston,et al.  Oat cell carcinoma of the bronchus and the carcinoid syndrome. , 1975, Archives of pathology.