Department of Cardiology, the Affiliated Hospital of Southwest Medical University and Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, and Collaborative Innovation Center for Prevention of Cardiovascular Diseases, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, 646000, China.
Department of Cardiovascular Surgery, Affiliated Hospital of Southwest Medical University, Southwest Medical University, Luzhou, 646000, China.
Biol Trace Elem Res. 2024 Feb;202(2):481-492. doi: 10.1007/s12011-023-03683-3. Epub 2023 Apr 29.
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.
氧化锌纳米颗粒（ZnO NPs）由于其独特的物理化学性质而被广泛应用于许多领域。然而，ZnO NPs 的肾毒性及其潜在机制尚未得到充分研究。我们发现，ZnO NPs 以剂量和尺寸依赖的方式诱导人肾近端肾小管上皮细胞（HK-2）损伤，这一点通过 CCK-8、LDH 和 Annexin V-FITC 检测得以证实。在机制上，ZnO NPs 通过产生 ROS 促进氧化应激和线粒体损伤，并诱导 HK-2 细胞凋亡，这一点表现在 Bax 和 Caspase 3 的上调以及 Beclin 1 的下调。在体内，ZnO NPs 诱导肾小管上皮细胞凋亡，并增加小鼠血清肌酐、血清尿素氮和尿蛋白，表明肾脏结构和功能受损。这些发现阐明了我们对 ZnO NP 诱导的肾小管上皮细胞损伤的生物学机制的理解，并有助于评估 ZnO NPs 对肾脏的风险。
