Background: Zinc oxide nanoparticles have been utilized in different fields over the last decades. These nanoparticles can pose significant risks to various organs such as the liver. This study aimed to evaluate the effects of zinc oxide nanoparticles on liver histology, serum biochemistry, and spatial arrangement of the hepatocytes in the female New Zealand white rabbit.

Methods: The rabbits received 1, 5, and 10 mg/kg of the zinc oxide nanoparticles (ZnO NPs) intraperitoneally once every 3 days for 28 days. The serum levels of the aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and zinc were assessed 48 hr following the first administration. The histopathological changes and Voronoi tessellation were evaluated after the last administration.

Results: Our findings showed that the ZnO NPs significantly increased the serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and zinc. The histopathological findings showed ballooning degeneration, and sinusoidal congestion in ZnO NPs administrated groups. The Voronoi tessellation diagrams also confirmed that ZnO NPs changed the regular spatial arrangement of hepatocytes to random and cluster patterns.

Conclusion: In conclusion, the ZnO NPs alter the liver spatial arrangement and induce hepatic pathological changes that may affect liver function in rabbits.