Hepatotoxicity and the role of the gut-liver axis in dogs after oral administration of zinc oxide nanoparticles.

Zinc oxide nanoparticles (ZnO NPs) have been used in many fields, and people are concerned about its effects on health. The present study reported the changes in liver metabolites and intestinal microbiota induced by overused ZnO NPs in dogs and explored the related mechanisms of liver injury induced by ZnO NPs. The results showed that overused ZnO NPs promote zinc accumulation in the liver and increase liver coefficient and serum liver-related indexes. In addition, the overuse of ZnO NPs increase the reactive oxygen species levels, affecting the hepatocyte antioxidant capacity and mitochondrial function. Results showed that ZnO NPs significantly inhibited the hepatocyte apoptosis via the Cytc pathway and promoted the autophagy via activating the mTOR/ATG5 pathway. Metabolic analysis of liver tissue showed that 81 metabolites changed overall and mainly affected the glycerophospholipid metabolism. ZnO NPs can significantly change the richness and diversity of the intestinal bacteria in dogs, increasing the abundance of Firmicutes and Actinobacteria while reducing the bacterial abundance of Proteobacteria. In conclusion, the results suggest that overexposure to ZnO NPs can lead to the disruption of intestinal microbiome and liver metabolites in dogs, which ultimately leads to liver damage.