Respiratory Exposure to Copper Oxide Particles Causes Multiple Organ Injuries via Oxidative Stress in a Rat Model

作者：Kaifang Wang, Xin Ning, Chuanyue Qin, Jianlin Wang, Wenjie Yan, Xin Zhou, Deping Wang, Ji-Min Cao, Yanlin Feng · 发表于：International Journal of Nanomedicine · 年份：2022 · DOI：10.2147/ijn.s378727 · 被引用次数：21 · 研究领域：Nanoparticles: synthesis and applications、Copper-based nanomaterials and applications、Advanced Nanomaterials in Catalysis

Introduction: The wide application of copper oxide nanoparticles (CuO NPs) in industry, agriculture, environmental remediation, and biomedicine has increased the risk of human exposure to CuO NPs. Recent studies suggested that CuO NPs have genotoxic and cytotoxic effects on various cells. However, little is known about the toxicity of CuO NPs on major peripheral organs after respiratory exposure. Materials and Methods: We investigated the toxicities of CuO NPs on human bronchial epithelial (BEAS-2B) and human cardiomyocytes (AC16) cells in vitro, and on the lungs, liver, kidneys, and heart of spontaneously hypertensive rats (SHRs) at 24 and 72 h after intrabronchial instillation in vivo. Results: CuO NPs induced concentration-dependent toxicities in both BEAS-2B and AC16 cells mainly through hierarchical oxidative stress mechanisms, involving generation of reactive oxygen species (ROS), upregulation of heme oxygenase-1 (HO-1), mitochondrial dysfunction, and secretion of proinflammatory and profibrogenic cytokines. Respiratory exposure to CuO NPs induced acute multiple organ injuries in SHRs manifesting through inflammation and fibrosis. However, cardiac injury was relatively less severe than injuries in the lungs, liver, and kidneys. Upregulation of serum C-reaction protein (CRP), tumor necrosis factor α (TNF-α), intercellular adhesion molecule 1 (ICAM-1), endothelin-1 (ET-1), angiotensin converting enzyme (ACE), and von Willebrand factor (vWF) after exposure to CuO NPs indic...