Department of Pathology, The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, PR China.
Department of Emergency, Xiang'An Hospital of Xiamen University, Xiamen, Fujian, PR China.
Toxicol In Vitro. 2020 Dec;69:104967. doi: 10.1016/j.tiv.2020.104967. Epub 2020 Aug 14.
With the increased use of nanomaterials and increased exposure of humans to various nanomaterials, the potential health effects of nanomaterials cannot be ignored. The hepatotoxicity of cobalt nanoparticles (Nano-Co) is largely unknown and the underlying mechanisms remain obscure. The purpose of this study was to exam the hepatotoxicity induced by Nano-Co and its potential mechanisms. Our results showed that exposure of human fetal hepatocytes L02 to Nano-Co caused a dose- and a time-dependent cytotoxicity. Besides the generation of reactive oxygen species (ROS) and mitochondrial reactive oxygen species (mtROS), exposure to Nano-Co also caused activation of NOD-like receptor protein 3 (NLRP3) inflammasome in hepatocytes. After silencing NLRP3, one component of NLRP3 inflammasome, expression by siRNA strategy, we found that upregulation of NLRP3-related proteins was abolished in hepatocytes exposed to Nano-Co. Using antioxidants to scavenge ROS and mtROS, we demonstrated that Nano-Co-induced mtROS generation was related to Nano-Co-induced NLRP3 inflammasome activation. Our findings demonstrated that Nano-Co exposure may promote intracellular oxidative stress damage, and mtROS may mediate the activation of NLRP3 inflammasome in hepatocytes exposed to Nano-Co, suggesting an important role of ROS/NLRP3 pathway in Nano-Co-induced hepatotoxicity. These results provide scientific insights into the hepatotoxicity of Nano-Co and a basis for the prevention and treatment of Nano-Co-induced cytotoxicity.
随着纳米材料的广泛应用和人类对各种纳米材料的接触增加，纳米材料的潜在健康影响不容忽视。钴纳米颗粒（Nano-Co）的肝毒性在很大程度上是未知的，其潜在的机制仍不清楚。本研究旨在研究 Nano-Co 诱导的肝毒性及其潜在机制。我们的研究结果表明，人胎肝细胞 L02 暴露于 Nano-Co 可引起剂量和时间依赖性细胞毒性。除了活性氧（ROS）和线粒体活性氧（mtROS）的产生外，Nano-Co 还可激活肝细胞中的 NOD 样受体蛋白 3（NLRP3）炎性体。通过 siRNA 策略沉默 NLRP3 后，我们发现暴露于 Nano-Co 中的肝细胞中 NLRP3 炎性体的一种成分的 NLRP3 相关蛋白的表达被上调。使用抗氧化剂清除 ROS 和 mtROS，我们证明了 Nano-Co 诱导的 mtROS 生成与 Nano-Co 诱导的 NLRP3 炎性体激活有关。我们的研究结果表明，Nano-Co 暴露可能会促进细胞内氧化应激损伤，mtROS 可能介导暴露于 Nano-Co 的肝细胞中 NLRP3 炎性体的激活，提示 ROS/NLRP3 途径在 Nano-Co 诱导的肝毒性中起重要作用。这些结果为 Nano-Co 的肝毒性提供了科学见解，并为预防和治疗 Nano-Co 诱导的细胞毒性提供了依据。
