Zinc oxide nanoparticles induce renal injury by initiating oxidative stress, mitochondrial damage and apoptosis in renal tubular epithelial cells

Abstract

Abstract 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 has not been well elucidated. Here we found that ZnO NPs induced injury of human renal proximal tubular epithelial cells (HK-2) in a dose- and size-dependent manner, as revealed by CCK-8, LDH and AnnexinV-FITC assay. Mechanistically, ZnO NPs promoted oxidative stress and mitochondrial damage by generating ROS, and finallyinduced apoptosis of HK-2 cells, as evidenced by upregulation of Bax and Caspase 3 and downregulation of Beclin 1. In vivo, ZnO NPs induced tubular epithelial cell apoptosis and elevations of serum creatinine, serum urea nitrogen, and urinary protein in mice suggesting damage of renal structure and function. Collectively, this study demonstrated that oral intake of ZnO NPs induced nephrotoxicity both in vitro and in vivo mainly via inducing oxidative stress, mitochondrial damage and apoptosis in the tubular epithelial cells.