Activation of NLRP3 inflammasome in hepatocytes after exposure to cobalt nanoparticles: The role of oxidative stress.

Abstract 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.