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

BACKGROUND: Cerium oxide (CeO(2)) nanoparticles have been posited to have both beneficial and toxic effects on biological systems. Herein, we examine if a single intratracheal instillation of CeO(2) nanoparticles is associated with systemic toxicity in male Sprague-Dawley rats. METHODS AND RESULTS: Compared with control animals, CeO(2) 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 CeO(2) 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 CeO(2) nanoparticles. CONCLUSION: Taken together, these data suggest that intratracheal instillation of CeO(2) nanoparticles can result in liver damage.