Toxicity Induced by Zirconia Oxide Nanoparticles on Various Organs After Intravenous Administration in Rats

ZrO2-NPs are widely applied in industry, biomedicine and dentistry, e.g., foundry sands, refractories, ceramics dental prostheses, dental implant coatings and bone defect restorative materials. To date, little information is available on the potential adverse effects and toxic mechanism in human organs associated with exposure to ZrO2-NPs. The biodistribution of ZrO2-NPs and the consequent oxidative stress in the spleen, kidney, heart, brain, and lung at six time points after a single injection of ZrO2-NPs were examined. Histopathological and immunohistochemical changes were also examined. RNA-Seq analysis was conducted in organs with high ZrO2-NPs accumulations or obvious histopathological changes (brain and spleen). Exposure to the ZrO2-NPs led to persistent oxidative stress and cell proliferation promotion/inhibition in various organs. RNA-Seq results of the spleen and brain point to significant gene expression changes. Metabolism was identified as leading pathways in the spleen. This study proves ZrO2-NPs likely have negative impacts on various organs, and exhibit potential disease risks.