Zinc Oxide Nanoparticles Induce Renal Injury by Initiating Oxidative Stress, Mitochondrial Damage and Apoptosis in Renal Tubular Epithelial Cells.

Zinc oxide nanoparticles (ZnO NPs) are widely used in many fields due to their unique physicochemical properties. However, the renal toxicity of ZnO NPs and the underlying mechanisms have not been well studied. We found that ZnO NPs induced injury in human renal proximal tubular epithelial cells (HK-2) in a dose- and size-dependent manner, as revealed by CCK-8, LDH and Annexin V-FITC assays. Mechanistically, ZnO NPs promoted oxidative stress and mitochondrial damage by generating ROS and induced apoptosis in HK-2 cells, as evidenced by the upregulation of Bax and Caspase 3 and downregulation of Beclin 1. In vivo, ZnO NPs induced tubular epithelial cell apoptosis and increased serum creatinine, serum urea nitrogen, and urinary protein in mice, suggesting damage to renal structure and function. These findings clarified our understanding of the biological mechanisms underlying ZnO NP-induced renal tubular epithelial cell injury and contributed to estimating the risk of ZnO NPs to the kidney.